Identification of a family of human F-box proteins.
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F-box proteins (including the WD40-class Fbws such as FBW2/FBXW2) are substrate-recruiting subunits of SCF ubiquitin ligases composed of SKP1, a cullin (CUL1), ROC1/RBX1 and the F-box protein, bringing E2 enzymes to specifically recruited substrates.
ATF4 degradation relies on a phosphorylation-dependent interaction with the SCF(betaTrCP) ubiquitin ligase.
M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFbeta-TrCP.
Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics.
Cyclin F-mediated degradation of ribonucleotide reductase M2 controls genome integrity and DNA repair.
Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition.
FBXW7-mediated degradation of CCDC6 is impaired by ATM during DNA damage response in lung cancer cells.
RACK1 (receptor for activated C-kinase 1) interacts with FBW2 (F-box and WD-repeat domain-containing 2) to up-regulate GCM1 (glial cell missing 1) stability and placental cell migration and invasion.
A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways.
A High-Density Map for Navigating the Human Polycomb Complexome.
DCAF8, a novel MuRF1 interaction partner, promotes muscle atrophy.
A reference map of the human binary protein interactome.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
The SCF Complex Is Essential to Maintain Genome and Chromosome Stability.
The role of ubiquitination and deubiquitination in tumor invasion and metastasis.
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FBXW2 is a substrate-recognition receptor of the SCF E3 ligase that suppresses proliferation and invasion of lung cancer cells by targeting SKP2 and β-catenin; it is itself a substrate of β-TrCP1 (forming the β-TrCP1-FBXW2-SKP2 axis), and in hepatocellular carcinoma targets TAK1 for K48-linked polyubiquitination and degradation.
Multimodal cell maps as a foundation for structural and functional genomics.
Falcon deep research report for human FBXW2
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FBXW2 functions as an SCF substrate adaptor that binds specific substrates (often phosphorylation-dependently) and promotes their polyubiquitination and proteasome-dependent degradation.
"FBXW2's primary biochemical function is as an **SCF substrate adaptor** that binds specific protein substrates (often in a phosphorylation-dependent manner) and promotes their **polyubiquitination** leading to **proteasome-dependent degradation**."
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FBXW2 is both a substrate of SCF(β-TrCP1) and an E3 substrate receptor for SKP2, forming a β-TrCP1-FBXW2-SKP2 F-box cascade in which β-TrCP1 recognizes FBXW2 via a conserved SSGART motif.
"β-TrCP1 recognition of FBXW2 involves a conserved motif (reported as **SSGART**) with phospho-dependent binding to the β-TrCP consensus"
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FBXW2 recognizes β-catenin after EGF-AKT1 phosphorylation at Ser552 via a TSXXXS-like degron, driving β-catenin ubiquitylation and proteasomal degradation and suppressing migration/invasion in lung cancer.
"**EGF–AKT1 signaling** phosphorylates β-catenin at **Ser552**, enabling FBXW2 binding."
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FBXW2 directly ubiquitinates NF-κB p65/RELA at K122 in a phosphorylation-dependent manner antagonized by p300-mediated acetylation, suppressing breast cancer stemness and paclitaxel resistance.
"The study identifies **p65 K122** as an FBXW2 ubiquitination site, and reports that **p300-mediated acetylation** inhibits FBXW2-induced p65 ubiquitination"
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FBXW2 directs K48-linked polyubiquitination of Moesin, an interaction weakened by AKT phosphorylation of Moesin at Thr558, tying FBXW2 to an AKT-Moesin-SKP2 oncogenic axis.
"FBXW2 directs **Lys-48-linked polyubiquitination** of Moesin, consistent with proteasome-targeting chains."
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
Interaction of E3 with substrate and E2-Ub complex