Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
The hypoxia-controlled FBXL14 ubiquitin ligase targets SNAIL1 for proteasome degradation.
PKD1 phosphorylation-dependent degradation of SNAIL by SCF-FBXO11 regulates epithelial-mesenchymal transition and metastasis.
A High-Density Map for Navigating the Human Polycomb Complexome.
Architecture of the human interactome defines protein communities and disease networks.
A reference map of the human binary protein interactome.
The FBXL family of F-box proteins: variations on a theme.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
Identification of an E3 ligase that targets the catalytic subunit of RNA Polymerase I upon transcription stress.
Multimodal cell maps as a foundation for structural and functional genomics.
AcM-UBE2M transfers NEDD8 to CRL1 E3 ubiquitin ligase complex
NEDD8:AcM-UBE2M binds CRL1 E3 ubiquitin ligase complex
CAND1 binds cytosolic CRL E3 ubiquitin ligases
COMMDs displace CAND1 from cytosolic CRL E3 ubiquitin ligase complexes
COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes
MyrG-DCUN1D3 binds CRL1 E3 ubiquitin ligase complex
Transfer of Ub from E2 to substrate and release of E2
Release of E3 from polyubiquitinated substrate
Polyubiquitination of substrate
Falcon deep research report for human FBXL14
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FBXL14 is an SCF (CRL1) substrate receptor that promotes ubiquitin-dependent proteasomal degradation of select transcriptional regulators, with validated direct substrates HES1 and SNAIL1.
"FBXL14 is best supported as an **SCF (CRL1) E3 ubiquitin ligase substrate receptor** that promotes **ubiquitin-dependent proteasomal degradation** of select transcriptional regulators, with validated direct substrates including **HES1** (Notch signaling effector) and **SNAIL1** (EMT transcription factor)."
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SCF(FBXL14) recognizes the conserved C-terminal WRPW motif of the Notch effector HES1, which is required for HES1 binding, ubiquitination, and degradation.
"the conserved **C-terminal WRPW motif** in HES1 is required for FBXL14 binding and for SCF^FBXL14-mediated ubiquitination and degradation; deleting WRPW reduces co-IP with FBXL14, increases HES1 stability in CHX chase, and decreases polyubiquitination."
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SCF(FBXL14) ubiquitinates SNAIL1 on acceptor lysines K98, K137 and K146, with a triple K-to-R mutant strongly stabilized, and depletion of FBXL14 extends SNAIL1 half-life from about 1 h to about 3 h.
"Major SNAIL1 ubiquitination acceptor lysines include **K98, K137, K146**: a triple mutant shows reduced ubiquitination and is highly stable (e.g., ~80% remaining after 4 h CHX in cited experiments)."
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Hypoxia down-regulates FBXL14 mRNA in a TWIST1-dependent manner, stabilizing SNAIL1 protein without increasing SNAI1 mRNA and thereby supporting EMT.
"TWIST1 is required for this hypoxia response: Twist1 knockdown prevents hypoxia-induced FBXL14 down-modulation and prevents SNAIL1 stabilization."
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FBXL14 is reported to ubiquitinate Thr58-phosphorylated c-MYC, promoting differentiation and suppressing glioma stem-cell tumorigenicity (review-summarized primary evidence).
"FBXL14 is reported to ubiquitylate **Thr58-phosphorylated c-Myc**; FBXL14 is low in glioma stem cells but higher in non-stem-like glioma cells/neural progenitors."
Interaction of E3 with substrate and E2-Ub complex