WIPF1 (WASP-Interacting Protein 1) – Structure, Function, and Recent Insights OpenAI o3-deep-research-2025-06-26 138 citations 2025-12-27T21:54:02.778331

WIPF1 (WASP-Interacting Protein 1) – Structure, Function, and Recent Insights

Overview and Key Concepts

WIPF1 (WAS/WASL-Interacting Protein Family Member 1), often called Wiskott–Aldrich Syndrome Protein-Interacting Protein (WIP), encodes a 503–amino-acid adaptor protein crucial for actin cytoskeleton organization (en.wikipedia.org). First identified in 1997, WIP was shown to induce actin polymerization and cytoskeletal reorganization in lymphoid cells (en.wikipedia.org). It belongs to the verprolin family of actin-binding proteins, reflecting its evolutionary conservation (e.g. yeast Vrp1/verprolin is a homolog) (www.reactome.org). WIPF1 is expressed ubiquitously in humans (with high levels in immune tissues like blood cells, spleen, thymus, and also placenta) (www.reactome.org). Notably, WIP is named for its interaction with the Wiskott–Aldrich Syndrome protein (WASp); this interaction underpins WIP’s biological role and links it to the immunodeficiency disorder Wiskott–Aldrich syndrome (en.wikipedia.org). In cells, WIP functions as a scaffold/adaptor that links signaling molecules to the actin polymerization machinery, rather than as an enzyme – it has no catalytic activity, but its binding partners and domains enable it to regulate actin dynamics in space and time.

Protein domains and structure: WIPF1’s protein product contains several defined motifs that mediate its interactions (see Figure 1 for domain map). It has an N-terminal profilin-binding domain, which can bind profilin–actin complexes (en.wikipedia.org). Profilin is an actin-monomer binding protein, so this interaction helps tether actin monomers. WIP also contains two WH2 (Wiscott–Aldrich homology 2) domains (verprolin homology motifs) that directly bind globular actin (G-actin) (en.wikipedia.org). These WH2 domains allow WIP to sequester or position actin monomers near sites of filament assembly. A central proline-rich region enables WIP to bind SH3-domain proteins – for example, it can bind to the adaptor Nck and other SH3-containing partners (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Finally, the C-terminus of WIP contains a WASP-binding domain that binds tightly to the N-terminal EVH1 (WH1) domain of WASP and N-WASP (en.wikipedia.org). This WIP–WASP interaction is constitutive (WIP and WASP form a stable complex in resting cells) and is functionally critical: most disease-causing mutations in WASP occur in its EVH1 domain and disrupt WIP binding (en.wikipedia.org). Structural studies have shown that a 25-residue segment of WIP wraps around the EVH1 domain of N-WASP/WASP, forming an extensive interface; this explains why many Wiskott–Aldrich Syndrome mutations (EVH1 missense mutations) destabilize the WIP–WASP complex (pubmed.ncbi.nlm.nih.gov). In the absence of WIP, WASP is unstable and prone to degradation, as observed in both WIP-deficient patients and knockout models (rupress.org). Thus, WIP’s domains collectively allow it to bind actin monomers, actin-polymerization factors (profilin), and key regulators like WASP/N-WASP, positioning WIP as a central organizer of actin assembly.

Role in Actin Polymerization and Cytoskeletal Regulation

WIP is best understood for its role in regulating actin polymerization through the Arp2/3 complex pathway. WASP and N-WASP (the proteins that WIP binds) are actin nucleation-promoting factors: upon activation, WASP/N-WASP use their C-terminal VCA domain to activate the Arp2/3 complex, which in turn nucleates new actin filaments (creating branched actin networks) (pmc.ncbi.nlm.nih.gov). WIP itself does not nucleate actin, but it modulates this process by controlling the availability and activity of WASP/N-WASP and actin monomers at the membrane. In resting cells, WIP bound to WASP can help keep WASP in an inactive but stable state – preventing its degradation yet also potentially masking interactions until the right signals arrive (en.wikipedia.org) (rupress.org). When an upstream signal (for example, from a cell-surface receptor) triggers Cdc42 or other pathways that activate WASP/N-WASP, WIP participates in recruiting and localizing WASP to the proper subcellular site (www.reactome.org). WIP works together with adaptor proteins like Nck and Grb2 to target WASP/N-WASP to the plasma membrane or to forming actin structures (www.reactome.org). Notably, WIP’s interaction with Nck (via its proline-rich motif binding Nck’s SH3 domain) couples receptor signaling to actin polymerization: Nck is often recruited to phosphorylated receptor complexes, and it can carry WIP–WASP complexes with it (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This positioning allows WASP to encounter its activators (like Cdc42 or PIP₂) at the membrane and then trigger Arp2/3-mediated actin assembly.

Influence on actin structures: By tethering WASP/N-WASP and actin, WIP orchestrates the formation of specialized actin-rich structures. For example, filopodia (spike-like membrane protrusions) and lamellipodia (broad membrane ruffles) are both actin-driven structures that require coordinated nucleation and elongation of actin filaments. WIP promotes filopodium formation in cooperation with N-WASP under the control of active Cdc42 (pmc.ncbi.nlm.nih.gov). In addition, WIP is required for efficient lamellipodia formation in response to stimuli like PDGF (Platelet-Derived Growth Factor) (pmc.ncbi.nlm.nih.gov). Mechanistically, WIP–WASP complexes at the leading edge help initiate new actin branches via Arp2/3, while also possibly disassembling older actin stress fibers, thus shifting the cytoskeletal architecture from contractile bundles to protrusive networks (www.reactome.org). In vitro and cellular overexpression studies support WIP’s pro-polymerizing role: overexpressing WIP in mammalian cells enhances actin polymerization and drives redistribution of actin filaments (en.wikipedia.org). Conversely, when WIP is removed or mutated, cells show defective actin assembly – for instance, WIP-deficient fibroblasts or immune cells have trouble forming normal lamellipodia and filopodia, highlighting WIP’s indispensable role in actin network formation (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Importantly, WIP can also bind actin directly via its WH2 domains, and this direct WIP–actin interaction is biologically essential. An elegant study in knockout mice demonstrated that T cells expressing a WIP mutant unable to bind actin (but still able to bind WASP) exhibit severe cytoskeletal defects (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). These WIP mutant T cells maintained normal WASP levels (since WIP still bound WASP to stabilize it) but had reduced F-actin content, disorganized filament architecture, and impaired cell polarization and migration (pmc.ncbi.nlm.nih.gov). They failed to crawl normally and could not home to lymphoid organs effectively (pmc.ncbi.nlm.nih.gov). This indicates that WIP’s direct binding to actin monomers or filaments is needed to maintain the integrity of the actin cytoskeleton in cells. By binding actin, WIP may cluster actin monomers near WASP, facilitating efficient nucleation and elongation. Additionally, WIP-bound actin might help anchor the WIP–WASP complex to existing filaments, aiding branching. Thus, both arms of WIP’s function – bridging to WASP and directly binding actin – converge to promote proper actin polymerization.

Localization and Interactions of WIPF1 Protein

Subcellular localization: WIP is predominantly a cytosolic protein that concentrates at areas of active actin remodeling. It lacks transmembrane domains and does not enter the secretory pathway, so it functions inside the cell. Studies have shown that WIP co-localizes with actin filaments – for example, it is seen along actin stress fibers in fibroblasts and at the cortical actin network in various cells (www.reactome.org). When WIP is expressed with N-WASP, it tends to accumulate in the same regions as N-WASP (e.g. at the cell periphery and in perinuclear puncta), rather than along bundled actin, reflecting the formation of WIP–WASP complexes that relocate together (www.reactome.org). WIP is also found at specialized actin structures: it localizes to the invadopodia of cancer cells and podosomes of normal cells (these are actin-rich adhesive protrusions – described further below) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Furthermore, WIP can associate with vesicular membranes that are undergoing actin-driven movement. One striking example is during vaccinia virus infection: vaccinia hijacks the host actin machinery to propel itself, forming “actin comet tails” on the virus. WIP is actively recruited to vaccinia virions on endosomal membranes and serves as an adapter to bring N-WASP to the virus surface, enabling actin polymerization that drives the virus through the cell (www.reactome.org). In cells lacking WIP or WASP, vaccinia virus motility is greatly impaired, underscoring WIP’s role in linking actin to membrane-bound cargos (www.reactome.org). In summary, WIP is usually found in the cytoplasm at or near the plasma membrane, wherever dynamic actin assembly is occurring (ruffles, microvilli, immune synapses, etc.), rather than in the nucleus or extracellular space.

Protein–protein interactions: As an adaptor, WIPF1 protein interacts with numerous partners to execute its function. Its primary binding partner is WASP (in hematopoietic cells) or N-WASP (ubiquitously) (en.wikipedia.org). WIP forms a tight complex with WASP via the C-terminus, and similarly can bind N-WASP (WASL) in other cell types (en.wikipedia.org). Beyond WASP, WIP binds actin (G-actin and possibly F-actin) and profilin–actin complexes as noted. WIP’s proline-rich segment allows it to engage several SH3-domain-containing signaling adaptors. Key among these is Nck1, an adapter that links receptor tyrosine kinases or T-cell receptor signaling to actin regulation; WIP and Nck1 interact directly, which helps recruit the WIP–WASP complex to activated receptors (en.wikipedia.org) (pmc.ncbi.nlm.nih.gov). WIP also binds the Cortactin protein (en.wikipedia.org) – cortactin is an actin-binding scaffolding protein enriched in invadopodia and at the immunological synapse. Through binding cortactin, WIP may help coordinate actin polymerization with matrix degradation, since cortactin scaffolds the machinery that brings metalloproteinases (MMPs) to invasive protrusions (pmc.ncbi.nlm.nih.gov). Another known WIP partner is NCK/ITSN1 (Intersectin-1), an endocytic adaptor; WIP might participate in endocytosis or receptor trafficking via this interaction (en.wikipedia.org). WIP binds MYO1e (myosin 1e) (en.wikipedia.org), an unconventional myosin that links actin to membranes, suggesting WIP could help attach actin filaments to membrane structures during movement. Additionally, WIP interacts with FNBP1L (Toca-1) (www.reactome.org), an SH3-domain protein that, together with N-WASP, is involved in endocytic vesicle formation and actin nucleation. Through FNBP1L and the related protein ITSN, WIP–WASP may be recruited to sites of clathrin-mediated endocytosis, promoting actin assembly for vesicle internalization (www.reactome.org). WIP’s N-terminal region (residues 45–48) contains a KLKK motif that binds actin (pmc.ncbi.nlm.nih.gov), and also a profilin-binding site, highlighting how WIP can simultaneously connect to monomeric actin (via KLKK/WH2) and profilin–actin complexes. This multiplicity of interactions enables WIP to serve as a hub where signaling molecules (like Nck, protein kinases), actin regulators (profilin, cortactin), and actin itself all converge.

Biological Functions in Immune Cells and Beyond

One of the most critical roles of WIPF1 is in the immune system, where its interplay with WASP is vital for immune cell function. WASP is expressed only in blood lineage cells (leukocytes), and WIP is highly expressed in these cells as well (en.wikipedia.org). In T lymphocytes, WIP is essential for forming the immune synapse – the specialized junction between a T cell and an antigen-presenting cell. During T cell activation, the T cell receptor (TCR) triggers a burst of actin polymerization at the contact site, creating a platform for signaling. WIP is required to concentrate F-actin at the edge of the immunological synapse, enabling the T cell to spread and form a tight contact (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Experiments show that WIP-deficient T cells cannot properly polarize their actin cytoskeleton upon TCR engagement, leading to an impaired synapse and reduced signaling (e.g. poor IL-2 secretion) (pmc.ncbi.nlm.nih.gov). In WIP knockout mice, T cells proliferate poorly in response to stimulation and fail to sustain contact with antigen-presenting cells (pmc.ncbi.nlm.nih.gov). This is because without WIP, WASP is absent (degraded) and Arp2/3-driven actin nucleation is greatly compromised, so the T cell can’t reorganize its cytoskeleton effectively. Interestingly, while WIP positively regulates T-cell activation (by promoting actin remodeling at the synapse), it has an opposite effect in B cells: WIP acts as a negative regulator of B-cell receptor signaling. WIP-deficient B cells show enhanced proliferation and upregulated activation markers upon B-cell receptor stimulation (pmc.ncbi.nlm.nih.gov). In WIP knockout mice, B cells produce abnormally high levels of IgM and IgE antibodies and tend to hyper-respond, which is associated with autoimmune symptoms (pmc.ncbi.nlm.nih.gov). This dichotomy suggests WIP helps maintain a balance in the immune system: it’s required for full T-cell activation, but also serves to restrain B-cell activation to prevent overreaction. The net result in WIP-deficient mice is a mix of immunodeficiency (due to T-cell dysfunction) and autoimmune features (due to unrestrained B cells) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Other immune cells are also affected: Natural Killer (NK) cells from WIP-deficient patients fail to properly polarize lytic granules towards their targets, leading to defective cytotoxicity (pmc.ncbi.nlm.nih.gov). Similarly, dendritic cells and macrophages rely on WIP for forming podosomes – actin-rich adhesive structures needed for migration and tissue invasion (pmc.ncbi.nlm.nih.gov). Without WIP, these myeloid cells can’t form normal podosomes, impairing processes like wound healing and immune cell trafficking (pmc.ncbi.nlm.nih.gov).

Beyond the immune system, WIP participates in various cellular processes that require actin remodeling. In the nervous system, studies in mice suggest WIP has a role in regulating neurite outgrowth. Neurons from WIP-knockout mice showed accelerated neurite initiation and excessive branching, implying that WIP normally acts as a brake on early neurite formation (pmc.ncbi.nlm.nih.gov). The mechanism appears to involve signaling crosstalk: WIP deficiency led to overactivation of mTORC1–S6K signaling, which promotes neurite growth (pmc.ncbi.nlm.nih.gov). Thus, WIP might link actin dynamics to signaling pathways that control neural development, ensuring proper timing of neurite extension. In the context of pathogen infection, as mentioned, WIP is co-opted by vaccinia virus to facilitate its spread (www.reactome.org). There is evidence that other pathogens may also exploit WIP or its partners for actin-based motility: for instance, certain intracellular bacteria (like Listeria or Shigella) and viruses create actin “comet tails,” and proteins like N-WASP/WIP are often involved (pmc.ncbi.nlm.nih.gov). WIP’s ability to localize actin polymerization activity makes it a target for such viral/bacterial strategies to move within cells. Additionally, WIP is involved in cell migration generally. Fibroblasts lacking WIP have motility defects; conversely, WIP overexpression can increase cell migration speed (though often with less directional persistence) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). WIP also contributes to the formation of invadopodia in cancer cells – these are invasive protrusions that degrade extracellular matrix. We will discuss this further in the disease context, but biologically, invadopodia are similar to the podosomes of immune cells, and WIP–N-WASP–Arp2/3 are key components of both (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In summary, WIPF1’s normal functions span any cellular context where actin remodeling is critical: immune synapse assembly, cell migration, morphogenesis (neurite formation), and membrane trafficking. Its role is to ensure actin polymerization occurs at the right place and is integrated with the cell’s signaling cues.

Clinical Significance and Disease Associations

Immunodeficiency (WIPF1 mutations): Given WIP’s central partnership with WASP, it is unsurprising that defects in WIPF1 can lead to immunological disease resembling Wiskott–Aldrich Syndrome (WAS). WAS is an X-linked disorder caused by WASP mutations; patients have eczema, recurrent infections, thrombocytopenia (low platelets), and T-cell/B-cell dysfunction. In 2012, the first human case of WIPF1 deficiency was reported: a young girl with a WAS-like syndrome but no mutation in her WAS gene (en.wikipedia.org) (en.wikipedia.org). Genetic analysis found a homozygous loss-of-function mutation in WIPF1 (en.wikipedia.org). This WIP-deficient patient presented with severe recurrent infections, eczema, and thrombocytopenia – closely mirroring classic WAS (en.wikipedia.org). Cellular analysis confirmed that in the absence of WIP, WASP protein was completely depleted, explaining the immunodeficient phenotype (rupress.org). The patient’s T cells showed instability of the actin cytoskeleton and failed immune synapse formation, and NK cells had defective granule polarization (pmc.ncbi.nlm.nih.gov), consistent with what WIP-knockout mice predicted. A second case series in 2017 (Pfajfer et al.) identified additional patients with WIPF1 mutations, who likewise showed combined immunodeficiency and some developmental delays (pmc.ncbi.nlm.nih.gov). These cases establish WIPF1 deficiency as a rare primary immunodeficiency disorder. From a clinical standpoint, if a patient exhibits WAS-like symptoms but tests negative for WAS gene mutations, sequencing of WIPF1 is warranted. There is no official name for this condition yet (sometimes it’s considered within the WAS spectrum); treatment has involved bone marrow transplantation, similar to WAS (rupress.org). Notably, most WIP-deficient patients have undetectable WASP protein, confirming that WIP is essential for WASP stability in vivo (rupress.org). Even partial loss of WIP function (e.g. a mutation that weakens WIP–actin binding without fully ablating the protein) can impair immune cell function significantly (pmc.ncbi.nlm.nih.gov). Thus, WIPF1 is as critical as WASP for healthy immune function, and it underscores how adaptor proteins can be linchpins in signaling pathways.

Cancer and metastasis: Emerging research shows that WIPF1 also plays important roles in cancer cell behavior, particularly in cell migration, invasion, and metastasis. Many cancers exhibit dysregulated actin cytoskeleton dynamics to facilitate tumor spread, and WIP appears to be a key permissive factor for this. In most solid tumors, studies have found that WIP is upregulated and contributes to aggressive tumor phenotypes (pmc.ncbi.nlm.nih.gov). High WIP expression has been correlated with advanced disease and poorer patient outcomes in several cancer types, including lung, gastric, pancreatic, and others (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). For example, a 2023 analysis in gastric cancer patients showed that tumors with elevated WIPF1 levels were associated with worse prognosis (shorter overall survival) (pmc.ncbi.nlm.nih.gov). Functional experiments in gastric cancer cell lines demonstrated that WIP drives tumor progression by enhancing PI3K–Akt signaling in a myocardin-dependent manner (pmc.ncbi.nlm.nih.gov). When WIPF1 was knocked down in these cancer cells, their proliferation, migration, and invasiveness all decreased, supporting WIP as a pro-tumor factor (pmc.ncbi.nlm.nih.gov). Similarly, in non-small cell lung cancer (NSCLC), high WIP was linked to greater malignancy: one mechanism involves PD-L1 (an immune checkpoint protein) triggering β-catenin signaling which upregulates WIPF1, thereby promoting tumor cell survival and colony formation (pmc.ncbi.nlm.nih.gov). In lung adenocarcinoma models (A549 cells), overexpression of WIP induced a more mesenchymal and invasive phenotype, with increased cell motility and markers of epithelial–mesenchymal transition (EMT) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Conversely, reducing WIP in these cells can reverse some of the invasive characteristics (pmc.ncbi.nlm.nih.gov).

WIP’s role in invasion is tied to its function in forming invadopodia – the actin-rich protrusions by which cancer cells degrade and penetrate the extracellular matrix. WIP, together with N-WASP, is required for invadopodium formation and maturation (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In breast cancer cells, for instance, loss of WIP impairs the formation of functional invadopodia, reducing matrix degradation and cell invasion (pmc.ncbi.nlm.nih.gov). WIP recruits and interacts with cortactin and Nck in invadopodia, similar to its role in immune cell podosomes, to organize the actin core and to localize matrix metalloproteinase (MMP) delivery to the proper sites (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This is one reason WIP overexpression often confers metastatic potential: tumors can more readily break through tissue barriers. On a signaling level, WIP has been implicated in activating YAP/TAZ, the effectors of the Hippo pathway, which promote cell proliferation and survival. Research in pancreatic ductal adenocarcinoma found that microRNAs which suppress WIP led to reduced YAP/TAZ activity and less tumor invasion, while high WIP correlated with shorter patient survival (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In summary, high WIPF1 levels in tumors create a cellular environment conducive to metastasis: stronger actin-based motility, more invasive structures, and enhanced pro-survival signaling. This has made WIP of interest as a potential biomarker for cancer prognosis (pmc.ncbi.nlm.nih.gov). Indeed, WIPF1 is included in some gene signatures predicting poor outcome and therapy resistance in cancers such as head-neck squamous carcinoma and others (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). It’s important to note that WIP’s role can be context-dependent – intriguingly, some hematological cancers (leukemias/lymphomas) show the opposite trend, where WIP might act as a suppressor of tumor growth (pmc.ncbi.nlm.nih.gov). The reasons are not fully clear, but it might relate to WIP’s role in immune cells: for instance, WIP deficiency can cause hyper-activation of B cells, so loss of WIP in a B-cell lineage malignancy could conceivably promote proliferation. Nonetheless, the predominant theme in solid tumors is that WIP promotes tumor progression. From a therapeutic angle, targeting WIPF1 or its binding interfaces (e.g. disrupting WIP–WASP or WIP–actin interactions) is a novel idea. No WIP-targeted therapies exist yet, but researchers speculate that inhibiting WIP function might reduce cancer invasiveness and could be synergistic with therapies like immune checkpoint blockade (given the PD-L1–WIP connection) (pmc.ncbi.nlm.nih.gov).

Development and other contexts: A recent line of research has identified WIPF1 as important in developmental invasion processes, such as placental development. A 2023 study highlighted that WIPF1 is highly expressed in human placental extravillous trophoblasts (EVTs) during the first trimester (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). EVTs invade the uterine lining to establish blood supply for the fetus, a process conceptually similar to cell invasion in cancer (but tightly regulated). WIPF1 was found to be crucial for proper EVT invasion: knockdown of WIPF1 in trophoblast cells significantly impaired their migration and invasion, while overexpression enhanced invasion (pubmed.ncbi.nlm.nih.gov). WIP was shown to form a complex with actinin-4 (ACTN4), and this WIP–ACTN4 complex is involved in forming podosomes in trophoblasts, which are needed for establishing anchorage in the uterus (the study linked WIPF1 deficits to cases of recurrent spontaneous abortion) (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). This finding underscores WIP’s role in physiological invasion processes and suggests that beyond disease, WIP is required for normal human development (in this case, successful pregnancy). Another context being explored is WIP’s role in redox homeostasis in cancer cells: for instance, in glioblastoma, WIP was found to stabilize the transcription factor NRF2 (a master antioxidant regulator) by altering actin dynamics that affect the KEAP1–NRF2 degradation pathway (pmc.ncbi.nlm.nih.gov). This indicates WIP’s influence may extend to signaling pathways beyond actin itself (e.g., impacting gene expression indirectly via cytoskeletal changes). Overall, the involvement of WIPF1 in diverse contexts – immune function, development, cancer – all pivot on its core function of regulating the actin cytoskeleton. In each scenario, the precise role of WIPF1 is to localize and modulate actin polymerization in concert with specific partners, thereby enabling cellular processes like synapse formation, migration, or invasion.

Recent Developments and Expert Perspectives (2023–2024)

Research on WIPF1 has been active, with several 2023–2024 studies and reviews providing new insights. A notable publication in late 2024 (Alonso-Eiras & Antón, Cytoskeleton, Sep 2024) reviewed WIP’s roles and described it as a “double-edged sword” in pathology (pmc.ncbi.nlm.nih.gov). According to this review, WIP needs to be tightly regulated in the body: both an absence of WIP and an excess of WIP can lead to disease (pmc.ncbi.nlm.nih.gov). On one hand, loss-of-function mutations in WIPF1 cause severe immunodeficiency in humans (early-onset infections, autoimmunity, etc.), consistent with WIP’s essential role in the immune system (pmc.ncbi.nlm.nih.gov). On the other hand, overexpression of WIP is linked to cancer progression and even aging-related pathologies (pmc.ncbi.nlm.nih.gov). This duality is prompting researchers to dissect context-specific effects – for instance, why WIP overexpression is pro-tumorigenic in most solid cancers, yet WIP might restrain certain leukemias (pmc.ncbi.nlm.nih.gov). The 2024 review emphasizes that WIP performs some functions independent of actin polymerization, such as stabilizing the oncogenic transcription co-activators YAP/TAZ, which could contribute to tumor growth even when actin dynamics are not limiting (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The authors highlight the need for further research to identify WIP’s binding partners in various contexts and to explore if WIP could be a drug target in oncology (pmc.ncbi.nlm.nih.gov). They also note WIP’s involvement in fundamental processes, labeling it a “major regulator of actin dynamics with essential roles for a healthy immune system” (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

From a data perspective, recent studies have provided quantitative links between WIPF1 expression and clinical outcomes. For example, Su et al. (2023) reported that gastric cancer patients with high WIPF1 expression had significantly lower 5-year survival rates compared to those with low expression (pmc.ncbi.nlm.nih.gov). In pancreatic cancer, analysis of The Cancer Genome Atlas (TCGA) data showed that low WIPF1 expression correlated with longer overall survival, whereas high WIPF1 was a marker of poor prognosis (p < 0.01) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Large-scale profiling has also identified WIPF1 as part of an “EMT gene signature” that predicts metastasis; WIPF1 was flagged as a differentially expressed hub gene in head and neck cancers that progress versus those that do not (pmc.ncbi.nlm.nih.gov). Such bioinformatic and clinical studies underscore WIPF1’s relevance as a biomarker. In immunology, a 2023 study on WIP-knockout mice (Gadjalova et al., 2024) reinforced earlier findings by showing WIP deficiency leads to systemic autoimmunity (e.g. colitis and aberrant lymphocyte populations) due to cytoskeletal dysregulation in immune cells (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This suggests that therapies modulating actin regulators like WIP could potentially alleviate certain inflammatory conditions, though this idea is still speculative.

Another fresh development is the exploration of WIPF1 in reproductive medicine, as mentioned. The identification of WIPF1’s role in trophoblast invasion (2023) opens doors to investigating whether WIPF1 mutations or dysregulation contribute to pregnancy disorders such as recurrent miscarriages or preeclampsia. This is an example of how new research extends WIP’s significance beyond the immune and cancer fields.

Expert opinions: Leaders in the field, such as Dr. Inés Antón (a co-discoverer of WIP and author of multiple WIP studies), note that WIP is “a master coordinator of actin reorganization” and that its proper function is crucial for cellular health (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Her analyses point out that WIP’s multi-domain structure allows it to integrate signals – from Rho GTPases like Cdc42, to kinases, to membrane phospholipids – and translate them into precise actin assembly events (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Another expert perspective (from the 2024 Cytoskeleton review) is that targeting the WIP/WASP interface might be an attractive strategy in cases ranging from immunodeficiency to cancer (pmc.ncbi.nlm.nih.gov). For instance, stabilizing WIP–WASP interaction might help in conditions where WASP is unstable (as a therapeutic approach for certain WAS patients), whereas inhibiting WIP–WASP or WIP–actin interactions might slow down cancer cell invasion (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). However, such interventions would require extreme caution given WIP’s ubiquity and importance in normal cells.

In conclusion, WIPF1 encodes a pivotal actin-regulatory adaptor that connects the Wiskott–Aldrich Syndrome protein (WASP) to the actin cytoskeleton and to signaling networks. Its primary function is to coordinate actin filament nucleation and remodeling at specific cellular sites, enabling processes like immune synapse formation, cell motility, and invasion. WIPF1 operates at the nexus of multiple pathways: it interacts with key signaling proteins (Nck, GRB2, cortactin), structural proteins (actin, profilin), and membrane components, thereby serving as a bridge between signals and the actin machinery. This precise role has broad implications – loss of WIPF1 cripples immune cell function and causes immunodeficiency, while excess WIPF1 endows cells with enhanced invasive capabilities and is linked to metastasis and poor clinical outcomes in cancer. Current research (2023–2024) is actively uncovering new facets of WIPF1, from its involvement in placental development to its regulation of transcription factors in cancer, highlighting that WIPF1’s influence extends beyond actin polymerization alone. Moving forward, WIPF1 remains a subject of intense study, both to fully delineate how this protein maintains cellular cytoskeletal health and to exploit its dysfunction in disease contexts for potential therapies. Each new discovery reinforces the concept that controlling the actin cytoskeleton through molecules like WIPF1 is fundamental to cell biology and human health (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

References: (Publication dates and sources)
- Kolluri R. et al. (1997). “WIP, a protein associated with Wiskott–Aldrich syndrome protein, induces actin polymerization and redistribution in lymphoid cells.” Proc Natl Acad Sci USA 94(26):14671–14676 (en.wikipedia.org).
- Lanzi G. et al. (2012). “A novel primary human immunodeficiency due to deficiency in the WASP-interacting protein WIP.” J. Exp. Med. 209(1):29–34 (Jan 16, 2012) (en.wikipedia.org) (rupress.org).
- Massaad M. et al. (2014). “Binding of WIP to actin is essential for T cell actin cytoskeleton integrity and tissue homing.” Mol. Cell. Biol. 34(23):4343–54 (Dec 2014) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).
- Su F. et al. (2023). “WIP promotes tumor progression by regulating PI3K/Akt signaling in gastric cancer.” Cell. Oncol. 46(8):1063–1080 (Aug 2023) (pmc.ncbi.nlm.nih.gov).
- Alonso-Eiras J., Antón I.M. (2024). “Multifaceted role of the actin-binding protein WIP: promoter and inhibitor of tumor progression and dissemination.” Cytoskeleton 82(3):186–196 (Sep 27, 2024) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).
(Additional citations are embedded in text above for specific claims and data.)

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  4. AnnotationURLCitation(end_index=1321, start_index=1144, title='Reactome | UniProt:O43516 WIPF1', type='url_citation', url='https://www.reactome.org/content/schema/instance/browser/uniprot%3AO43516#:~:text=cortical%20areas%20like%20WASL%20,Belongs%20to%20the%20verprolin%20family')
  5. AnnotationURLCitation(end_index=1681, start_index=1535, title='WIPF1', type='url_citation', url='https://en.wikipedia.org/wiki/WIPF1#:~:text=to%20increase%20actin%20polymerization,depleted%20and%20WAS%20symptoms%20present')
  6. AnnotationURLCitation(end_index=2318, start_index=2204, title='WIPF1', type='url_citation', url='https://en.wikipedia.org/wiki/WIPF1#:~:text=affect%20WASp,WASp%20remains%20stable%20in%20the')
  7. AnnotationURLCitation(end_index=2672, start_index=2558, title='WIPF1', type='url_citation', url='https://en.wikipedia.org/wiki/WIPF1#:~:text=affect%20WASp,WASp%20remains%20stable%20in%20the')
  8. AnnotationURLCitation(end_index=3041, start_index=2933, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=breast%20cancer%20,2016')
  9. AnnotationURLCitation(end_index=3239, start_index=3042, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=For%20effective%20proteolysis%20of%20the,transcriptional%20activator%20E26%20transformation%20specific%E2%80%901')
  10. AnnotationURLCitation(end_index=3495, start_index=3381, title='WIPF1', type='url_citation', url='https://en.wikipedia.org/wiki/WIPF1#:~:text=affect%20WASp,WASp%20remains%20stable%20in%20the')
  11. AnnotationURLCitation(end_index=3817, start_index=3715, title='WIPF1', type='url_citation', url='https://en.wikipedia.org/wiki/WIPF1#:~:text=N,WASp%20remains%20stable%20in%20the')
  12. AnnotationURLCitation(end_index=4225, start_index=4076, title='Structure of the N-WASP EVH1 domain-WIP complex: insight into the molecular basis of Wiskott-Aldrich Syndrome - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/12437929/#:~:text=Missense%20mutants%20that%20cause%20the,This%20recognition%20mechanism')
  13. AnnotationURLCitation(end_index=4490, start_index=4360, title='A novel primary human immunodeficiency due to deficiency in the WASP-interacting protein WIP | Journal of Experimental Medicine | Rockefeller University Press', type='url_citation', url='https://rupress.org/jem/article-abstract/209/1/29/40968#:~:text=%28Fig,to%20examine%20whether%20transduction%20of')
  14. AnnotationURLCitation(end_index=5301, start_index=5135, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=match%20at%20L87%20Cdc42%20activates,to%20move%20through%20interstitial%20tissues')
  15. AnnotationURLCitation(end_index=5806, start_index=5660, title='WIPF1', type='url_citation', url='https://en.wikipedia.org/wiki/WIPF1#:~:text=to%20increase%20actin%20polymerization,depleted%20and%20WAS%20symptoms%20present')
  16. AnnotationURLCitation(end_index=5937, start_index=5807, title='A novel primary human immunodeficiency due to deficiency in the WASP-interacting protein WIP | Journal of Experimental Medicine | Rockefeller University Press', type='url_citation', url='https://rupress.org/jem/article-abstract/209/1/29/40968#:~:text=%28Fig,to%20examine%20whether%20transduction%20of')
  17. AnnotationURLCitation(end_index=6302, start_index=6157, title='Reactome | UniProt:O43516 WIPF1', type='url_citation', url='https://www.reactome.org/content/schema/instance/browser/uniprot%3AO43516#:~:text=,Vesicle%20surfaces%20and%20along%20actin')
  18. AnnotationURLCitation(end_index=6588, start_index=6443, title='Reactome | UniProt:O43516 WIPF1', type='url_citation', url='https://www.reactome.org/content/schema/instance/browser/uniprot%3AO43516#:~:text=,Vesicle%20surfaces%20and%20along%20actin')
  19. AnnotationURLCitation(end_index=7034, start_index=6837, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=For%20effective%20proteolysis%20of%20the,transcriptional%20activator%20E26%20transformation%20specific%E2%80%901')
  20. AnnotationURLCitation(end_index=7159, start_index=7035, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=al,MMP2%2C%20and%20MMP9%20is%20produced')
  21. AnnotationURLCitation(end_index=7931, start_index=7756, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=formation%20of%20actin%E2%80%90rich%20structures%20including,A%20WIP%2FWASP%20complex%20is')
  22. AnnotationURLCitation(end_index=8244, start_index=8069, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=formation%20of%20actin%E2%80%90rich%20structures%20including,A%20WIP%2FWASP%20complex%20is')
  23. AnnotationURLCitation(end_index=8645, start_index=8500, title='Reactome | UniProt:O43516 WIPF1', type='url_citation', url='https://www.reactome.org/content/schema/instance/browser/uniprot%3AO43516#:~:text=,Vesicle%20surfaces%20and%20along%20actin')
  24. AnnotationURLCitation(end_index=8991, start_index=8848, title='WIPF1', type='url_citation', url='https://en.wikipedia.org/wiki/WIPF1#:~:text=This%20gene%20encodes%20a%20protein,depleted%20and%20WAS%20symptoms%20present')
  25. AnnotationURLCitation(end_index=9378, start_index=9256, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=WIP%20is%20not%20necessary%20for,2002')
  26. AnnotationURLCitation(end_index=9544, start_index=9379, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=polarization%20%28Ant%C3%B3n%20et%20al,immune%20system%20have%20been%20partially')
  27. AnnotationURLCitation(end_index=10001, start_index=9858, title='Binding of WIP to Actin Is Essential for T Cell Actin Cytoskeleton Integrity and Tissue Homing - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4248745/#:~:text=The%20Wiskott,actin%20content%2C%20a%20disorganized%20actin')
  28. AnnotationURLCitation(end_index=10156, start_index=10002, title='Binding of WIP to Actin Is Essential for T Cell Actin Cytoskeleton Integrity and Tissue Homing - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4248745/#:~:text=that%20lack%20the%20actin,from%20WIP%CE%94ABD%20mice%20had%20decreased')
  29. AnnotationURLCitation(end_index=10503, start_index=10372, title='Binding of WIP to Actin Is Essential for T Cell Actin Cytoskeleton Integrity and Tissue Homing - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4248745/#:~:text=,defect%20in%20contact%20hypersensitivity%20and')
  30. AnnotationURLCitation(end_index=10739, start_index=10585, title='Binding of WIP to Actin Is Essential for T Cell Actin Cytoskeleton Integrity and Tissue Homing - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4248745/#:~:text=that%20lack%20the%20actin,from%20WIP%CE%94ABD%20mice%20had%20decreased')
  31. AnnotationURLCitation(end_index=11906, start_index=11711, title='Reactome | UniProt:O43516 WIPF1', type='url_citation', url='https://www.reactome.org/content/schema/instance/browser/uniprot%3AO43516#:~:text=the%20SH3%20domain%29%20%28PubMed%3A19798448%29,ALTERNATIVE%20PRODUCTS%20Highly%20expressed')
  32. AnnotationURLCitation(end_index=12350, start_index=12155, title='Reactome | UniProt:O43516 WIPF1', type='url_citation', url='https://www.reactome.org/content/schema/instance/browser/uniprot%3AO43516#:~:text=the%20SH3%20domain%29%20%28PubMed%3A19798448%29,ALTERNATIVE%20PRODUCTS%20Highly%20expressed')
  33. AnnotationURLCitation(end_index=12718, start_index=12563, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=Generation%20of%20several%20of%20the,in%20chromosome%202%20in%20humans')
  34. AnnotationURLCitation(end_index=12894, start_index=12719, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=formation%20of%20actin%E2%80%90rich%20structures%20including,A%20WIP%2FWASP%20complex%20is')
  35. AnnotationURLCitation(end_index=13552, start_index=13359, title='Reactome | UniProt:O43516 WIPF1', type='url_citation', url='https://www.reactome.org/content/schema/instance/browser/uniprot%3AO43516#:~:text=intracellular%20motility%20of%20vaccinia%20virus,Vesicle%20surfaces%20and%20along%20actin')
  36. AnnotationURLCitation(end_index=13888, start_index=13695, title='Reactome | UniProt:O43516 WIPF1', type='url_citation', url='https://www.reactome.org/content/schema/instance/browser/uniprot%3AO43516#:~:text=intracellular%20motility%20of%20vaccinia%20virus,Vesicle%20surfaces%20and%20along%20actin')
  37. AnnotationURLCitation(end_index=14464, start_index=14330, title='WIPF1', type='url_citation', url='https://en.wikipedia.org/wiki/WIPF1#:~:text=WIP%20has%20been%20shown%20to,terminal%20profilin%20binding%20domain')
  38. AnnotationURLCitation(end_index=14713, start_index=14579, title='WIPF1', type='url_citation', url='https://en.wikipedia.org/wiki/WIPF1#:~:text=WIP%20has%20been%20shown%20to,terminal%20profilin%20binding%20domain')
  39. AnnotationURLCitation(end_index=15280, start_index=15146, title='WIPF1', type='url_citation', url='https://en.wikipedia.org/wiki/WIPF1#:~:text=WIP%20has%20been%20shown%20to,terminal%20profilin%20binding%20domain')
  40. AnnotationURLCitation(end_index=15421, start_index=15281, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=molecules%20like%20the%20adaptor%20proteins,Vaduva%20et')
  41. AnnotationURLCitation(end_index=15598, start_index=15464, title='WIPF1', type='url_citation', url='https://en.wikipedia.org/wiki/WIPF1#:~:text=WIP%20has%20been%20shown%20to,terminal%20profilin%20binding%20domain')
  42. AnnotationURLCitation(end_index=16047, start_index=15912, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=match%20at%20L148%20is%20the,Invadopodia%20protein')
  43. AnnotationURLCitation(end_index=16347, start_index=16213, title='WIPF1', type='url_citation', url='https://en.wikipedia.org/wiki/WIPF1#:~:text=WIP%20has%20been%20shown%20to,terminal%20profilin%20binding%20domain')
  44. AnnotationURLCitation(end_index=16515, start_index=16381, title='WIPF1', type='url_citation', url='https://en.wikipedia.org/wiki/WIPF1#:~:text=WIP%20has%20been%20shown%20to,terminal%20profilin%20binding%20domain')
  45. AnnotationURLCitation(end_index=16922, start_index=16715, title='Reactome | UniProt:O43516 WIPF1', type='url_citation', url='https://www.reactome.org/content/schema/instance/browser/uniprot%3AO43516#:~:text=intracellular%20motility%20of%20vaccinia%20virus,spleen%2C%20placenta%2C%20small%20intestine%2C%20colon')
  46. AnnotationURLCitation(end_index=17413, start_index=17206, title='Reactome | UniProt:O43516 WIPF1', type='url_citation', url='https://www.reactome.org/content/schema/instance/browser/uniprot%3AO43516#:~:text=intracellular%20motility%20of%20vaccinia%20virus,spleen%2C%20placenta%2C%20small%20intestine%2C%20colon')
  47. AnnotationURLCitation(end_index=17639, start_index=17499, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=molecules%20like%20the%20adaptor%20proteins,Vaduva%20et')
  48. AnnotationURLCitation(end_index=18365, start_index=18280, title='WIPF1', type='url_citation', url='https://en.wikipedia.org/wiki/WIPF1#:~:text=N,These%20mutations')
  49. AnnotationURLCitation(end_index=18924, start_index=18802, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=WIP%20is%20not%20necessary%20for,2002')
  50. AnnotationURLCitation(end_index=19070, start_index=18925, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=appropriate%20immunological%20synapse%20formation%20and,2002')
  51. AnnotationURLCitation(end_index=19456, start_index=19267, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=WIP%E2%80%90deficient%20mice%20present%20impaired%20T%E2%80%90cell,in%20both%20T%20and%20B%E2%80%90cells')
  52. AnnotationURLCitation(end_index=19746, start_index=19592, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=WIP%E2%80%90deficient%20mice%20present%20impaired%20T%E2%80%90cell,23')
  53. AnnotationURLCitation(end_index=20420, start_index=20272, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=fully%20recreate%20the%20immunological%20synapse,Most%20initial')
  54. AnnotationURLCitation(end_index=20733, start_index=20585, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=fully%20recreate%20the%20immunological%20synapse,Most%20initial')
  55. AnnotationURLCitation(end_index=21260, start_index=21071, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=WIP%E2%80%90deficient%20mice%20present%20impaired%20T%E2%80%90cell,in%20both%20T%20and%20B%E2%80%90cells')
  56. AnnotationURLCitation(end_index=21424, start_index=21261, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=be%20a%20negative%20regulator%20of,detailing%20the%20human%20phenotype%20while')
  57. AnnotationURLCitation(end_index=21773, start_index=21624, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=%28Pfajfer%20et%20al,T%E2%80%90cells%20to%20localize%20WIP%20and')
  58. AnnotationURLCitation(end_index=22062, start_index=21930, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=enriched%20in%20F%E2%80%90actin,2013%29%2C%20in')
  59. AnnotationURLCitation(end_index=22325, start_index=22193, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=enriched%20in%20F%E2%80%90actin,2013%29%2C%20in')
  60. AnnotationURLCitation(end_index=22834, start_index=22699, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=match%20at%20L161%20on%20N%E2%80%90WASP,Ant%C3%B3n')
  61. AnnotationURLCitation(end_index=23117, start_index=22982, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=match%20at%20L161%20on%20N%E2%80%90WASP,Ant%C3%B3n')
  62. AnnotationURLCitation(end_index=23563, start_index=23370, title='Reactome | UniProt:O43516 WIPF1', type='url_citation', url='https://www.reactome.org/content/schema/instance/browser/uniprot%3AO43516#:~:text=intracellular%20motility%20of%20vaccinia%20virus,Vesicle%20surfaces%20and%20along%20actin')
  63. AnnotationURLCitation(end_index=24017, start_index=23832, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=match%20at%20L170%20Actin%20regulatory,of%20short%20bowel%20syndrome%2C%20ionophore%E2%80%90mediated')
  64. AnnotationURLCitation(end_index=24502, start_index=24371, title='Binding of WIP to Actin Is Essential for T Cell Actin Cytoskeleton Integrity and Tissue Homing - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4248745/#:~:text=,defect%20in%20contact%20hypersensitivity%20and')
  65. AnnotationURLCitation(end_index=24657, start_index=24503, title='Binding of WIP to Actin Is Essential for T Cell Actin Cytoskeleton Integrity and Tissue Homing - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4248745/#:~:text=that%20lack%20the%20actin,from%20WIP%CE%94ABD%20mice%20had%20decreased')
  66. AnnotationURLCitation(end_index=25172, start_index=24978, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=match%20at%20L74%20related%20actin%E2%80%90dependent,group%20of%20actin%E2%80%90rich%20degradative%20cellular')
  67. AnnotationURLCitation(end_index=25328, start_index=25173, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=Generation%20of%20several%20of%20the,in%20chromosome%202%20in%20humans')
  68. AnnotationURLCitation(end_index=26355, start_index=26209, title='WIPF1', type='url_citation', url='https://en.wikipedia.org/wiki/WIPF1#:~:text=between%20these%20two%20proteins%20may,depleted%20and%20WAS%20symptoms%20present')
  69. AnnotationURLCitation(end_index=26493, start_index=26356, title='WIPF1', type='url_citation', url='https://en.wikipedia.org/wiki/WIPF1#:~:text=This%20gene%20encodes%20a%20protein,levels%20are%20depleted%20and%20WAS')
  70. AnnotationURLCitation(end_index=26716, start_index=26570, title='WIPF1', type='url_citation', url='https://en.wikipedia.org/wiki/WIPF1#:~:text=between%20these%20two%20proteins%20may,depleted%20and%20WAS%20symptoms%20present')
  71. AnnotationURLCitation(end_index=26996, start_index=26850, title='WIPF1', type='url_citation', url='https://en.wikipedia.org/wiki/WIPF1#:~:text=to%20increase%20actin%20polymerization,depleted%20and%20WAS%20symptoms%20present')
  72. AnnotationURLCitation(end_index=27267, start_index=27137, title='A novel primary human immunodeficiency due to deficiency in the WASP-interacting protein WIP | Journal of Experimental Medicine | Rockefeller University Press', type='url_citation', url='https://rupress.org/jem/article-abstract/209/1/29/40968#:~:text=%28Fig,to%20examine%20whether%20transduction%20of')
  73. AnnotationURLCitation(end_index=27570, start_index=27421, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=%28Pfajfer%20et%20al,T%E2%80%90cells%20to%20localize%20WIP%20and')
  74. AnnotationURLCitation(end_index=27948, start_index=27803, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=protein%20%28Pfajfer%20et%20al,Further%20study%20of%20immune')
  75. AnnotationURLCitation(end_index=28482, start_index=28352, title='A novel primary human immunodeficiency due to deficiency in the WASP-interacting protein WIP | Journal of Experimental Medicine | Rockefeller University Press', type='url_citation', url='https://rupress.org/jem/article-abstract/209/1/29/40968#:~:text=%28Fig,to%20examine%20whether%20transduction%20of')
  76. AnnotationURLCitation(end_index=28747, start_index=28617, title='A novel primary human immunodeficiency due to deficiency in the WASP-interacting protein WIP | Journal of Experimental Medicine | Rockefeller University Press', type='url_citation', url='https://rupress.org/jem/article-abstract/209/1/29/40968#:~:text=%28Fig,to%20examine%20whether%20transduction%20of')
  77. AnnotationURLCitation(end_index=29056, start_index=28913, title='Binding of WIP to Actin Is Essential for T Cell Actin Cytoskeleton Integrity and Tissue Homing - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4248745/#:~:text=The%20Wiskott,actin%20content%2C%20a%20disorganized%20actin')
  78. AnnotationURLCitation(end_index=29812, start_index=29645, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=disease%2C%20focusing%20on%20cancer,Interestingly%2C%20a%20minority%20of%20studies')
  79. AnnotationURLCitation(end_index=30157, start_index=29977, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=A%20direct%20correlation%20of%20worse,signaling%20in%20a%20myocardin%E2%80%90dependent%20manner')
  80. AnnotationURLCitation(end_index=30333, start_index=30158, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=match%20at%20L563%20between%20WIP,tumorigenesis%2C%20like%20stabilization%20of%20YAP%2FTAZ')
  81. AnnotationURLCitation(end_index=30689, start_index=30509, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=A%20direct%20correlation%20of%20worse,signaling%20in%20a%20myocardin%E2%80%90dependent%20manner')
  82. AnnotationURLCitation(end_index=31043, start_index=30858, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=A%20direct%20correlation%20of%20worse,proliferative%20ability%2C%20migration%2C%20and%20invasiveness')
  83. AnnotationURLCitation(end_index=31352, start_index=31197, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=et%20al,proliferative%20ability%2C%20migration%2C%20and%20invasiveness')
  84. AnnotationURLCitation(end_index=31776, start_index=31626, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=prognosis%20%28Korman%20et%20al,human%20NSCLC%20cell%20line%20and')
  85. AnnotationURLCitation(end_index=32086, start_index=31983, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=al,NSCLC%29%20cell')
  86. AnnotationURLCitation(end_index=32239, start_index=32087, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=In%20a%20lung%20adenocarcinoma%20cell,basal%20BC%20cell%20line%20in')
  87. AnnotationURLCitation(end_index=32485, start_index=32330, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=et%20al,proliferative%20ability%2C%20migration%2C%20and%20invasiveness')
  88. AnnotationURLCitation(end_index=32875, start_index=32748, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=To%20invade%20and%20migrate%20through,2016')
  89. AnnotationURLCitation(end_index=33073, start_index=32876, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=For%20effective%20proteolysis%20of%20the,transcriptional%20activator%20E26%20transformation%20specific%E2%80%901')
  90. AnnotationURLCitation(end_index=33347, start_index=33220, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=To%20invade%20and%20migrate%20through,2016')
  91. AnnotationURLCitation(end_index=33765, start_index=33568, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=For%20effective%20proteolysis%20of%20the,transcriptional%20activator%20E26%20transformation%20specific%E2%80%901')
  92. AnnotationURLCitation(end_index=33901, start_index=33766, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=match%20at%20L148%20is%20the,Invadopodia%20protein')
  93. AnnotationURLCitation(end_index=34515, start_index=34390, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=Another%20lncRNA%20reported%20to%20be,62')
  94. AnnotationURLCitation(end_index=34691, start_index=34516, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=miR%E2%80%90141%20and%2C%20to%20a%20lesser,correlated%20significantly%20with%20longer%20OS')
  95. AnnotationURLCitation(end_index=35137, start_index=34962, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=match%20at%20L563%20between%20WIP,tumorigenesis%2C%20like%20stabilization%20of%20YAP%2FTAZ')
  96. AnnotationURLCitation(end_index=35453, start_index=35295, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=was%20a%20gene%20directly%20associated,identified%20WIPF1%20as%20a%20gene')
  97. AnnotationURLCitation(end_index=35620, start_index=35454, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=proteomics%2C%20is%20correlated%20with%20a,disease%20and%20shorter%20patient%20OS')
  98. AnnotationURLCitation(end_index=35999, start_index=35832, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=disease%2C%20focusing%20on%20cancer,Interestingly%2C%20a%20minority%20of%20studies')
  99. AnnotationURLCitation(end_index=36853, start_index=36703, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=prognosis%20%28Korman%20et%20al,human%20NSCLC%20cell%20line%20and')
  100. AnnotationURLCitation(end_index=37350, start_index=37161, title='Unraveling the role of the WIPF1/ACTN4 complex in podosome formation of human placental EVTs: Insights into recurrent spontaneous abortion - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/40821124/#:~:text=Successful%20placental%20development%20and%20pregnancy,involvement%20in%20successful%20placental%20development')
  101. AnnotationURLCitation(end_index=37492, start_index=37351, title='Unraveling the role of the WIPF1/ACTN4 complex in podosome formation of human placental EVTs: Insights into recurrent spontaneous abortion - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/40821124/#:~:text=exclusively%20expressed%20in%20first,derived%20EVTs%20hampered')
  102. AnnotationURLCitation(end_index=37983, start_index=37842, title='Unraveling the role of the WIPF1/ACTN4 complex in podosome formation of human placental EVTs: Insights into recurrent spontaneous abortion - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/40821124/#:~:text=exclusively%20expressed%20in%20first,derived%20EVTs%20hampered')
  103. AnnotationURLCitation(end_index=38450, start_index=38261, title='Unraveling the role of the WIPF1/ACTN4 complex in podosome formation of human placental EVTs: Insights into recurrent spontaneous abortion - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/40821124/#:~:text=Successful%20placental%20development%20and%20pregnancy,involvement%20in%20successful%20placental%20development')
  104. AnnotationURLCitation(end_index=38592, start_index=38451, title='Unraveling the role of the WIPF1/ACTN4 complex in podosome formation of human placental EVTs: Insights into recurrent spontaneous abortion - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/40821124/#:~:text=exclusively%20expressed%20in%20first,derived%20EVTs%20hampered')
  105. AnnotationURLCitation(end_index=39238, start_index=39065, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=regulator%20of%20cancer%20cells%20redox,to%20altered%20actin%20polymerization%20dynamics')
  106. AnnotationURLCitation(end_index=40275, start_index=40108, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=disease%2C%20focusing%20on%20cancer,Interestingly%2C%20a%20minority%20of%20studies')
  107. AnnotationURLCitation(end_index=40576, start_index=40418, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=match%20at%20L583%20in%20immune,date%2C%20a%20definitive%20link%20between')
  108. AnnotationURLCitation(end_index=40909, start_index=40771, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=invasiveness,overexpression%20of%20WIP%20has%20mostly')
  109. AnnotationURLCitation(end_index=41181, start_index=41023, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=match%20at%20L583%20in%20immune,date%2C%20a%20definitive%20link%20between')
  110. AnnotationURLCitation(end_index=41546, start_index=41379, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=disease%2C%20focusing%20on%20cancer,Interestingly%2C%20a%20minority%20of%20studies')
  111. AnnotationURLCitation(end_index=41976, start_index=41801, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=match%20at%20L563%20between%20WIP,tumorigenesis%2C%20like%20stabilization%20of%20YAP%2FTAZ')
  112. AnnotationURLCitation(end_index=42163, start_index=41977, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=between%20WIP%20overexpression%20and%20worse,tumorigenesis%2C%20like%20stabilization%20of%20YAP%2FTAZ')
  113. AnnotationURLCitation(end_index=42484, start_index=42329, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=overexpression%20and%20worse%20prognosis%2C%20mostly,2023%3B%20Li%20et')
  114. AnnotationURLCitation(end_index=42813, start_index=42646, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=biomarker%20for%20many%20solid%20tumors,with%20potential%20impact%20on%20prognosis')
  115. AnnotationURLCitation(end_index=42988, start_index=42814, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=WIP%27s%20principal%20role%20in%20lymphocytes,actin%20dynamics%20at%20the%20immunological')
  116. AnnotationURLCitation(end_index=43477, start_index=43297, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=A%20direct%20correlation%20of%20worse,signaling%20in%20a%20myocardin%E2%80%90dependent%20manner')
  117. AnnotationURLCitation(end_index=43860, start_index=43688, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=reduction%20of%20lung%20metastasis%20in,correlated%20significantly%20with%20longer%20OS')
  118. AnnotationURLCitation(end_index=44036, start_index=43861, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=miR%E2%80%90141%20and%2C%20to%20a%20lesser,correlated%20significantly%20with%20longer%20OS')
  119. AnnotationURLCitation(end_index=44426, start_index=44268, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=was%20a%20gene%20directly%20associated,identified%20WIPF1%20as%20a%20gene')
  120. AnnotationURLCitation(end_index=44955, start_index=44779, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=Murine%20WIP%20deficiency%20was%20associated,and%20T%E2%80%90cell%20activation%2C%20as%20it')
  121. AnnotationURLCitation(end_index=45145, start_index=44956, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=WIP%E2%80%90deficient%20mice%20present%20impaired%20T%E2%80%90cell,in%20both%20T%20and%20B%E2%80%90cells')
  122. AnnotationURLCitation(end_index=46122, start_index=45990, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=enriched%20in%20F%E2%80%90actin,2013%29%2C%20in')
  123. AnnotationURLCitation(end_index=46290, start_index=46123, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=biomarker%20for%20many%20solid%20tumors,with%20potential%20impact%20on%20prognosis')
  124. AnnotationURLCitation(end_index=46680, start_index=46505, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=formation%20of%20actin%E2%80%90rich%20structures%20including,A%20WIP%2FWASP%20complex%20is')
  125. AnnotationURLCitation(end_index=46803, start_index=46681, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=WIP%20is%20not%20necessary%20for,2002')
  126. AnnotationURLCitation(end_index=47151, start_index=46996, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=overexpression%20and%20worse%20prognosis%2C%20mostly,2023%3B%20Li%20et')
  127. AnnotationURLCitation(end_index=47564, start_index=47397, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=disease%2C%20focusing%20on%20cancer,Interestingly%2C%20a%20minority%20of%20studies')
  128. AnnotationURLCitation(end_index=47720, start_index=47565, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=et%20al,proliferative%20ability%2C%20migration%2C%20and%20invasiveness')
  129. AnnotationURLCitation(end_index=49493, start_index=49335, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=match%20at%20L583%20in%20immune,date%2C%20a%20definitive%20link%20between')
  130. AnnotationURLCitation(end_index=49668, start_index=49494, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=WIP%27s%20principal%20role%20in%20lymphocytes,actin%20dynamics%20at%20the%20immunological')
  131. AnnotationURLCitation(end_index=50047, start_index=49934, title='WIPF1', type='url_citation', url='https://en.wikipedia.org/wiki/WIPF1#:~:text=,interacting%20protein%20family%2C%20member%201')
  132. AnnotationURLCitation(end_index=50368, start_index=50222, title='WIPF1', type='url_citation', url='https://en.wikipedia.org/wiki/WIPF1#:~:text=between%20these%20two%20proteins%20may,depleted%20and%20WAS%20symptoms%20present')
  133. AnnotationURLCitation(end_index=50499, start_index=50369, title='A novel primary human immunodeficiency due to deficiency in the WASP-interacting protein WIP | Journal of Experimental Medicine | Rockefeller University Press', type='url_citation', url='https://rupress.org/jem/article-abstract/209/1/29/40968#:~:text=%28Fig,to%20examine%20whether%20transduction%20of')
  134. AnnotationURLCitation(end_index=50823, start_index=50680, title='Binding of WIP to Actin Is Essential for T Cell Actin Cytoskeleton Integrity and Tissue Homing - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4248745/#:~:text=The%20Wiskott,actin%20content%2C%20a%20disorganized%20actin')
  135. AnnotationURLCitation(end_index=50978, start_index=50824, title='Binding of WIP to Actin Is Essential for T Cell Actin Cytoskeleton Integrity and Tissue Homing - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC4248745/#:~:text=that%20lack%20the%20actin,from%20WIP%CE%94ABD%20mice%20had%20decreased')
  136. AnnotationURLCitation(end_index=51323, start_index=51138, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=A%20direct%20correlation%20of%20worse,proliferative%20ability%2C%20migration%2C%20and%20invasiveness')
  137. AnnotationURLCitation(end_index=51689, start_index=51530, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=Cancer%20cells%20depend%20on%20actin,and%20its%20contribution%20to%20human')
  138. AnnotationURLCitation(end_index=51857, start_index=51690, title='Multifaceted role of the actin‐binding protein WIP: Promotor and inhibitor of tumor progression and dissemination - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11904860/#:~:text=disease%2C%20focusing%20on%20cancer,Interestingly%2C%20a%20minority%20of%20studies')