Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Combined Automated Annotation using Multiple IEA Methods
M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFbeta-TrCP.
A critical role for FBXW8 and MAPK in cyclin D1 degradation and cancer cell proliferation.
Large-scale identification of c-MYC-associated proteins using a combined TAP/MudPIT approach.
The CUL7 E3 ubiquitin ligase targets insulin receptor substrate 1 for ubiquitin-dependent degradation.
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The CUL7(FBXW8) E3 ligase (CUL7, FBXW8, SKP1, ROC1/RBX1) targets IRS1 for ubiquitin-dependent degradation in an mTOR/p70-S6-kinase-dependent manner; Cul7-/- cells accumulate IRS1 with increased AKT and MEK/ERK signaling and undergo senescence-like phenotypes.
An OBSL1-Cul7Fbxw8 ubiquitin ligase signaling mechanism regulates Golgi morphology and dendrite patterning.
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CUL7(FBXW8) localizes to the Golgi (via OBSL1) and is required for Golgi morphology, secretory trafficking, and dendrite (not axon) elaboration in neurons; the Golgi stacking protein GRASP65/GORASP1 is a physiological substrate.
The CUL7/F-box and WD repeat domain containing 8 (CUL7/Fbxw8) ubiquitin ligase promotes degradation of hematopoietic progenitor kinase 1.
The 3M complex maintains microtubule and genome integrity.
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CUL7, OBSL1 and CCDC8 form a 3M complex (with which FBXW8 associates via CUL7) that maintains microtubule and genome integrity; CUL7 depletion causes microtubule defects, prometaphase arrest, tetraploidy and mitotic death.
A High-Density Map for Navigating the Human Polycomb Complexome.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
Structure of CRL7(FBXW8) reveals coupling with CUL1-RBX1/ROC1 for multi-cullin-RING E3-catalyzed ubiquitin ligation.
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Cryo-EM shows CUL7 binds FBXW8 in an F-box-independent mode; within CRL7(FBXW8) the RBX1 RING is held incompatible with E2~Ub/E2~NEDD8 binding, so the complex lacks intrinsic catalytic activity and instead acts as a substrate receptor coupled via SKP1-FBXW8 to a neddylated CUL1-RBX1 catalytic module.
Multimodal cell maps as a foundation for structural and functional genomics.
Falcon deep research report for human FBXW8
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Cryo-EM and reconstitution show CRL7(FBXW8) is an atypical multi-cullin E3 in which CUL7-FBXW8 recruits substrate while a neddylated CUL1-RBX1 module provides catalytic activity; recombinant CRL7(FBXW8) alone lacks auto-neddylation and ubiquitination activity.
"CUL7 binds FBXW8 in an F-box-independent mode; CRL7^FBXW8 alone lacks auto-neddylation/ubiquitination activity; catalytic coupling occurs to CUL1-RBX1"
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A Golgi-localized CUL7-FBXW8 complex directly binds adipose triglyceride lipase (ATGL/PNPLA2) and mediates its K48-linked polyubiquitylation and proteasomal degradation, restraining lipolysis; glucose depletion lowers Golgi PtdIns4P and reduces this degradation.
"Golgi-localized CUL7-FBXW8 directly interacts with ATGL and mediates K48-linked polyubiquitylation/proteasomal degradation"
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FBXW8 contains a polybasic N-terminal region that binds Golgi PtdIns4P, providing a phosphoinositide-sensing recruitment mechanism that couples intracellular glucose status to assembly of the CUL7-FBXW8 ligase at the Golgi.
"FBXW8 has a polybasic N-terminal region binding Golgi PtdIns4P; glucose deprivation lowers Golgi PtdIns4P, reduces FBXW8/CUL7 assembly at Golgi, stabilizes ATGL, and increases lipolysis"
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FBXW8 (in CUL7/FBXW8) promotes degradation of the nuclear chromatin-associated protein MRFAP1 specifically around anaphase-telophase, with FBXW8 overexpression increasing MRFAP1 polyubiquitination and knockdown prolonging its half-life.
"Cul7/FBXW8 promotes MRFAP1 degradation during anaphase-telophase; FBXW8 overexpression increases polyubiquitination and knockdown prolongs half-life"
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FBXW8 is essential in mouse models for mid-to-late placental development and fetal growth; Fbxw8 knockout causes intrauterine growth retardation and placental structural defects, with Fbxw8-null phenotypes milder than Cul7-null lethality.
"Loss causes intrauterine growth retardation, small placentas, reduced spongiotrophoblast/labyrinth abnormalities; placental defect depends on fetal genotype"
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