FBXL7

UniProt ID: Q9UJT9
Organism: Homo sapiens
Review Status: COMPLETE
📝 Provide Detailed Feedback

Gene Description

FBXL7 (F-box/LRR-repeat protein 7) is the substrate-recognition (F-box) subunit of an SCF (SKP1-CUL1-RBX1-F-box) cullin-RING E3 ubiquitin ligase that controls mitotic progression and apoptosis by directing the ubiquitination and proteasomal degradation of mitotic regulators. Within the SCF(FBXL7) complex, FBXL7 binds SKP1 via its F-box domain and uses its leucine-rich repeats to recruit substrates, so that CUL1-RBX1 drives their polyubiquitination. Its best-characterized substrates are the mitotic kinase Aurora A (AURKA), which FBXL7 colocalizes with and targets for centrosomal degradation during mitosis to promote mitotic arrest, and the inhibitor-of-apoptosis protein survivin/BIRC5 (recognized via survivin Glu126; ubiquitinated at Lys90/Lys91), whose FBXL7-mediated degradation regulates mitochondrial function and promotes apoptosis. FBXL7 (a 491-residue protein with an N-terminal F-box motif and roughly eleven C-terminal leucine-rich repeats) additionally targets active c-SRC (after Ser104 phosphorylation) and the EMT transcription factor SNAI1/Snail1 for degradation, acting as a metastasis suppressor that restrains SRC- and Snail1-driven epithelial-mesenchymal transition and invasion, and it ubiquitinates the glycolytic enzyme PFKFB4, coupling FBXL7 to metabolic reprogramming. FBXL7 localizes to the centrosome during spindle formation. FBXL7 is itself a proapoptotic factor whose cellular abundance is controlled by the related F-box protein FBXL18, which ubiquitinates FBXL7 (at Lys109) for proteasomal degradation, and its expression is repressed transcriptionally (e.g. by hypoxia-induced EZH2 and by promoter hypermethylation in cancer). Through these activities FBXL7 contributes to the G2/M transition, spindle dynamics, apoptotic signaling, EMT/metastasis suppression, and metabolic control, and is implicated in cancer progression and drug resistance.

Existing Annotations Review

GO Term Evidence Action Reason
GO:1990756 ubiquitin-like ligase-substrate adaptor activity
IDA
PMID:25778398
The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial...
NEW
Summary: Proposed core molecular function. As the F-box/LRR substrate-recognition subunit of SCF(FBXL7), FBXL7 selects substrates (AURKA, survivin/BIRC5) for SCF-dependent polyubiquitination. This more informative MF term is not in the GOA, which lacks any explicit MF annotation for FBXL7.
Reason: Captures the precise molecular function of FBXL7 as an SCF substrate-recognition adaptor, more informative than the bare protein binding annotations and absent from the existing GOA.
Supporting Evidence:
PMID:25778398
Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin by interacting with Glu-126 within its carboxyl-terminal α helix
GO:0005813 centrosome
IEA
GO_REF:0000120
ACCEPT
Summary: Combined automated electronic assignment of centrosome localization, where FBXL7 acts during spindle formation. Core localization for its mitotic role.
Reason: Core localization; FBXL7 localizes to the centrosome during spindle formation, consistent with its mitotic substrate-targeting role.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
KEEP AS NON CORE
Summary: Binary interactome reference map interactions. Bare protein binding is uninformative.
Reason: High-throughput interactome; bare protein binding is uninformative per curation guidelines.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
Q9UJT9; Q92609: TBC1D5; NbExp=3; IntAct=EBI-914660, EBI-742381
GO:0000086 G2/M transition of mitotic cell cycle
IEA
GO_REF:0000107
ACCEPT
Summary: Ortholog-based electronic assignment of involvement in the G2/M transition, consistent with FBXL7-driven AURKA degradation and mitotic arrest.
Reason: Core biological process; FBXL7 regulates mitotic progression (mitotic arrest via AURKA degradation).
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
During mitosis, it mediates the ubiquitination and subsequent proteasomal degradation of AURKA, causing mitotic arrest
GO:0000209 protein polyubiquitination
IEA
GO_REF:0000120
ACCEPT
Summary: Combined automated electronic assignment of protein polyubiquitination, the specific modification FBXL7 directs onto its substrates.
Reason: Correct; FBXL7 mediates substrate polyubiquitination, supported by IDA/IMP evidence (survivin).
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
regulates mitochondrial function by mediating the ubiquitination and proteasomal degradation of the apoptosis inhibitor BIRC5
GO:0000278 mitotic cell cycle
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Ortholog-based electronic assignment of involvement in the mitotic cell cycle, consistent with FBXL7's role in mitotic regulation.
Reason: Correct but generic relative to the specific G2/M transition and SCF-dependent degradation annotations.
Supporting Evidence:
PMID:25778398
Fbxl7, a component of the Skp1·Cul1·F-box protein type ubiquitin E3 ligase, regulates mitotic cell cycle progression
GO:0016567 protein ubiquitination
IEA
GO_REF:0000120
KEEP AS NON CORE
Summary: Combined automated electronic assignment of protein ubiquitination, a parent of the specific SCF-dependent polyubiquitination FBXL7 mediates.
Reason: Correct but generic; the specific SCF-dependent catabolic / polyubiquitination annotations better capture the role.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
PATHWAY: Protein modification; protein ubiquitination.
GO:0019005 SCF ubiquitin ligase complex
IEA
GO_REF:0000120
ACCEPT
Summary: Combined automated electronic assignment of SCF complex membership, the core assembly context for FBXL7.
Reason: Core cellular component; redundant with IDA/ISS evidence.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL7) composed of CUL1, SKP1, RBX1 and FBXL7
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
IEA
GO_REF:0000120
ACCEPT
Summary: Combined automated electronic assignment of SCF-dependent proteasomal degradation, the core biological process of SCF(FBXL7).
Reason: Core biological process; redundant with the experimental IDA/IMP evidence (survivin/AURKA degradation).
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
regulates mitochondrial function by mediating the ubiquitination and proteasomal degradation of the apoptosis inhibitor BIRC5
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
NAS
PMID:33234069
The FBXL family of F-box proteins: variations on a theme.
ACCEPT
Summary: Author-statement (FBXL family review) assignment of the core SCF-dependent proteasomal degradation process.
Reason: Core biological process; consistent with the experimental substrate-degradation evidence.
Supporting Evidence:
PMID:25778398
Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin
GO:0042981 regulation of apoptotic process
NAS
PMID:25654763
F-box protein Fbxl18 mediates polyubiquitylation and proteas...
ACCEPT
Summary: Author-statement (ComplexPortal) assignment of regulation of apoptosis; FBXL7 is a proapoptotic factor and its degradation of survivin/BIRC5 promotes apoptosis.
Reason: Supported biological process; FBXL7 is proapoptotic and regulates apoptosis via degradation of the IAP survivin/BIRC5.
Supporting Evidence:
PMID:25654763
Fbxl18 regulates apoptosis by mediating ubiquitin-dependent proteasomal degradation of the pro-apoptotic protein Fbxl7
GO:0000209 protein polyubiquitination
IMP
PMID:28218735
Aurora kinase A regulates Survivin stability through targeti...
ACCEPT
Summary: Mutant-phenotype evidence that FBXL7 mediates polyubiquitination of BIRC5/survivin. Core activity.
Reason: Directly supported substrate polyubiquitination (survivin/BIRC5); consistent with FBXL7's SCF substrate-receptor function.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
this interaction allows BIRC5 to be polyubiquitinated by the SCF(FBXL7) E3 ubiquitin-protein ligase complex
GO:0005515 protein binding
IPI
PMID:28218735
Aurora kinase A regulates Survivin stability through targeti...
KEEP AS NON CORE
Summary: Interaction with BIRC5/survivin (a FBXL7 substrate). Bare protein binding is uninformative.
Reason: Records the functionally important FBXL7-BIRC5 substrate interaction but bare protein binding is uninformative.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
Interacts with BIRC5; this interaction allows BIRC5 to be polyubiquitinated by the SCF(FBXL7)
GO:0019005 SCF ubiquitin ligase complex
IDA
PMID:25778398
The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial...
ACCEPT
Summary: Direct evidence that FBXL7 is a component of the SCF (SKP1-CUL1-F-box) E3 ligase complex. Core cellular component.
Reason: Core cellular component; FBXL7 is the F-box substrate receptor of the SCF(FBXL7) complex.
Supporting Evidence:
PMID:25778398
Fbxl7, a component of the Skp1·Cul1·F-box protein type ubiquitin E3 ligase, regulates mitotic cell cycle progression
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
IDA
PMID:25778398
The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial...
ACCEPT
Summary: Direct evidence that SCF(FBXL7) drives proteasomal degradation of survivin/BIRC5. Core biological process.
Reason: Core biological process directly demonstrated; FBXL7 targets survivin for SCF-dependent proteasomal degradation.
Supporting Evidence:
PMID:25778398
Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
IMP
PMID:28218735
Aurora kinase A regulates Survivin stability through targeti...
ACCEPT
Summary: Mutant-phenotype evidence linking FBXL7 to SCF-dependent degradation of survivin in the AURKA/gastric-cancer study. Core biological process.
Reason: Core biological process; FBXL7 mediates proteasomal degradation of survivin/BIRC5.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
regulates mitochondrial function by mediating the ubiquitination and proteasomal degradation of the apoptosis inhibitor BIRC5
GO:0000209 protein polyubiquitination
IDA
PMID:25778398
The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial...
ACCEPT
Summary: Direct evidence that FBXL7 polyubiquitinates survivin (at Lys90/Lys91). Core activity.
Reason: Directly demonstrated substrate polyubiquitination of survivin/BIRC5.
Supporting Evidence:
PMID:25778398
Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin
GO:0005515 protein binding
IPI
PMID:25778398
The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial...
KEEP AS NON CORE
Summary: Interaction with survivin (via Glu-126 in its C-terminal helix). Bare protein binding is uninformative.
Reason: Records the functionally important FBXL7-survivin substrate interaction but bare protein binding is uninformative.
Supporting Evidence:
PMID:25778398
Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin by interacting with Glu-126 within its carboxyl-terminal α helix
GO:0005829 cytosol
TAS
Reactome:R-HSA-8854051
KEEP AS NON CORE
Summary: Reactome curation of cytosolic localization (SCF-FBXL18 ubiquitinates FBXL7). Consistent with the cytoplasmic site of action.
Reason: Correct cytoplasmic compartment; the functionally salient localization is the centrosome during spindle formation.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005829 cytosol
TAS
Reactome:R-HSA-8854071
KEEP AS NON CORE
Summary: Reactome curation of cytosolic localization (proteasome-mediated degradation of PolyUb-FBXL7). Consistent with the cytoplasmic site of action.
Reason: Correct cytoplasmic compartment; the functionally salient localization is the centrosome.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005829 cytosol
TAS
Reactome:R-HSA-8853496
KEEP AS NON CORE
Summary: Reactome curation of cytosolic localization (SCF:FBXL7 binds AURKA). Consistent with the cytoplasmic site of action.
Reason: Correct cytoplasmic compartment; the functionally salient localization is the centrosome.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
During mitosis, it mediates the ubiquitination and subsequent proteasomal degradation of AURKA
GO:0005829 cytosol
TAS
Reactome:R-HSA-8854041
KEEP AS NON CORE
Summary: Reactome curation of cytosolic localization (SCF-FBXL7 ubiquitinates AURKA). Consistent with the cytoplasmic site of action.
Reason: Correct cytoplasmic compartment; the functionally salient localization is the centrosome.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
During mitosis, it mediates the ubiquitination and subsequent proteasomal degradation of AURKA
GO:0005829 cytosol
TAS
Reactome:R-HSA-8854044
KEEP AS NON CORE
Summary: Reactome curation of cytosolic localization (proteasome degrades AURKA ubiquitinated by SCF-FBXL7). Consistent with the cytoplasmic site of action.
Reason: Correct cytoplasmic compartment; the functionally salient localization is the centrosome.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
During mitosis, it mediates the ubiquitination and subsequent proteasomal degradation of AURKA
GO:0005829 cytosol
TAS
Reactome:R-HSA-8854052
KEEP AS NON CORE
Summary: Reactome curation of cytosolic localization (formation of the SCF-FBXL7 complex). Consistent with the cytoplasmic site of action.
Reason: Correct cytoplasmic compartment; the functionally salient localization is the centrosome.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL7) composed of CUL1, SKP1, RBX1 and FBXL7
GO:0005829 cytosol
TAS
Reactome:R-HSA-8952618
KEEP AS NON CORE
Summary: Reactome curation of cytosolic localization (neddylation of CRL1). Generic CRL-pathway localization.
Reason: Correct cytoplasmic compartment but from generic CRL neddylation-pathway context; the functionally salient localization is the centrosome.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005829 cytosol
TAS
Reactome:R-HSA-8952620
KEEP AS NON CORE
Summary: Reactome curation of cytosolic localization (NEDD8:UBE2M binds CRL1). Generic CRL-pathway localization.
Reason: Correct cytoplasmic compartment but from generic CRL-pathway context; redundant.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005829 cytosol
TAS
Reactome:R-HSA-8955241
KEEP AS NON CORE
Summary: Reactome curation of cytosolic localization (CAND1 binds cytosolic CRL). Generic CRL-pathway localization.
Reason: Correct cytoplasmic compartment but from generic CRL-regulation pathway context; redundant.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005829 cytosol
TAS
Reactome:R-HSA-8955289
KEEP AS NON CORE
Summary: Reactome curation of cytosolic localization (COMMDs displace CAND1). Generic CRL-pathway localization.
Reason: Correct cytoplasmic compartment but from generic CRL-regulation pathway context; redundant.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005829 cytosol
TAS
Reactome:R-HSA-8956040
KEEP AS NON CORE
Summary: Reactome curation of cytosolic localization (COP9 signalosome deneddylates CRL). Generic CRL-pathway localization.
Reason: Correct cytoplasmic compartment but from generic CRL-regulation pathway context; redundant.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005829 cytosol
TAS
Reactome:R-HSA-8956200
KEEP AS NON CORE
Summary: Reactome curation of cytosolic localization (DCUN1D3 binds CRL1). Generic CRL-pathway localization.
Reason: Correct cytoplasmic compartment but from generic CRL-regulation pathway context; redundant.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005829 cytosol
TAS
Reactome:R-HSA-983140
KEEP AS NON CORE
Summary: Reactome curation of cytosolic localization (transfer of Ub from E2 to substrate). Generic ubiquitination-pathway localization.
Reason: Correct cytoplasmic compartment but from generic ubiquitination-pathway context; redundant.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005829 cytosol
TAS
Reactome:R-HSA-983147
KEEP AS NON CORE
Summary: Reactome curation of cytosolic localization (release of E3 from polyubiquitinated substrate). Generic ubiquitination-pathway localization.
Reason: Correct cytoplasmic compartment but from generic ubiquitination-pathway context; redundant.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005829 cytosol
TAS
Reactome:R-HSA-983156
KEEP AS NON CORE
Summary: Reactome curation of cytosolic localization (polyubiquitination of substrate). Generic ubiquitination-pathway localization.
Reason: Correct cytoplasmic compartment but from generic ubiquitination-pathway context; redundant.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0005829 cytosol
TAS
Reactome:R-HSA-983157
KEEP AS NON CORE
Summary: Reactome curation of cytosolic localization (interaction of E3 with substrate and E2-Ub). Generic ubiquitination-pathway localization.
Reason: Correct cytoplasmic compartment but from generic ubiquitination-pathway context; redundant.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
GO:0000086 G2/M transition of mitotic cell cycle
ISS
GO_REF:0000024
ACCEPT
Summary: Sequence-similarity assignment of involvement in the G2/M transition, consistent with FBXL7-driven AURKA degradation.
Reason: Core biological process; FBXL7 regulates the mitotic G2/M transition.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
During mitosis, it mediates the ubiquitination and subsequent proteasomal degradation of AURKA, causing mitotic arrest
GO:0000278 mitotic cell cycle
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: Sequence-similarity assignment of involvement in the mitotic cell cycle.
Reason: Correct but generic relative to the specific G2/M transition annotation.
Supporting Evidence:
PMID:25778398
Fbxl7, a component of the Skp1·Cul1·F-box protein type ubiquitin E3 ligase, regulates mitotic cell cycle progression
GO:0005813 centrosome
ISS
GO_REF:0000024
ACCEPT
Summary: Sequence-similarity assignment of centrosome localization, where FBXL7 acts during spindle formation. Core localization.
Reason: Core localization; FBXL7 localizes to the centrosome during spindle formation.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
Localizes to the centrosome during spindle formation.
GO:0016567 protein ubiquitination
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: Sequence-similarity assignment of protein ubiquitination, a parent of the specific SCF-dependent polyubiquitination FBXL7 mediates.
Reason: Correct but generic; the specific polyubiquitination/SCF-dependent catabolic annotations better capture the role.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
PATHWAY: Protein modification; protein ubiquitination.
GO:0019005 SCF ubiquitin ligase complex
ISS
GO_REF:0000024
ACCEPT
Summary: Sequence-similarity assignment of SCF complex membership, the core assembly context for FBXL7.
Reason: Core cellular component; redundant with IDA/IEA evidence.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL7) composed of CUL1, SKP1, RBX1 and FBXL7
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
ISS
GO_REF:0000024
ACCEPT
Summary: Sequence-similarity assignment of SCF-dependent proteasomal degradation, the core biological process of SCF(FBXL7).
Reason: Core biological process; redundant with the experimental IDA/IMP evidence.
Supporting Evidence:
PMID:25778398
Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin
GO:0000151 ubiquitin ligase complex
NAS
PMID:10531035
Identification of a family of human F-box proteins.
KEEP AS NON CORE
Summary: Author-statement assignment (original F-box family paper) of being part of a ubiquitin ligase complex. A generic parent of the specific SCF complex.
Reason: Correct but generic; subsumed by the specific SCF ubiquitin ligase complex annotation.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL7)
GO:0006511 ubiquitin-dependent protein catabolic process
NAS
PMID:10531035
Identification of a family of human F-box proteins.
KEEP AS NON CORE
Summary: Author-statement assignment of ubiquitin-dependent protein catabolism, a parent of the specific SCF-dependent proteasomal degradation FBXL7 mediates.
Reason: Correct but generic; the specific GO:0031146 (SCF-dependent proteasomal catabolic process) better captures the role.
Supporting Evidence:
file:human/FBXL7/FBXL7-uniprot.txt
regulates mitochondrial function by mediating the ubiquitination and proteasomal degradation of the apoptosis inhibitor BIRC5

Core Functions

Functions as the substrate-recognition (F-box) subunit of an SCF (SKP1-CUL1-RBX1-FBXL7) cullin-RING E3 ubiquitin ligase that recruits the mitotic kinase Aurora A (AURKA) during mitosis for polyubiquitination and proteasomal degradation, contributing to control of the G2/M transition and mitotic progression.

Supporting Evidence:
  • file:human/FBXL7/FBXL7-uniprot.txt
    During mitosis, it mediates the ubiquitination and subsequent proteasomal degradation of AURKA, causing mitotic arrest

As the SCF(FBXL7) substrate receptor, binds the inhibitor-of-apoptosis protein survivin/BIRC5 and directs its polyubiquitination and proteasomal degradation, thereby regulating mitochondrial function and promoting apoptosis.

Supporting Evidence:
  • PMID:25778398
    Fbxl7 mediates polyubiquitylation and proteasomal degradation of survivin

As the SCF(FBXL7) substrate receptor, recognizes and directs the polyubiquitination and proteasomal degradation of additional substrates that drive epithelial-mesenchymal transition and metabolic reprogramming - active c-SRC (after Ser104 phosphorylation), the EMT transcription factor SNAI1/Snail1, and the glycolytic enzyme PFKFB4 - acting in cancer as a metastasis suppressor whose loss (via promoter hypermethylation or hypoxia/EZH2-driven transcriptional repression) promotes invasion and glycolysis. (Substrates beyond AURKA/survivin are reported in primary cancer literature summarized by the Falcon deep-research report and are not yet in the curated GOA.)

Supporting Evidence:
  • file:human/FBXL7/FBXL7-deep-research-falcon.md
    A high-impact cancer epigenetics study established FBXL7 as a **metastasis-suppressor axis component** through control of **active c-SRC**: FBXL7 mediates **ubiquitylation and proteasomal degradation of active c-SRC after phosphorylation at Ser104**, and loss of FBXL7 promotes EMT and metastasis.

References

Loading supporting content…

Download this section (compressed HTML)

Suggested Questions for Experts

Q: Are the two best-described FBXL7 substrates (AURKA and survivin/BIRC5) targeted by the same FBXL7 pool and cell-cycle window, or do distinct localizations (centrosomal versus cytosolic) and timing govern each substrate?

Q: How does the FBXL18-FBXL7 regulatory axis controlling FBXL7 abundance influence the balance between mitotic progression and apoptosis, and is it dysregulated in cancers with AURKA/survivin overexpression?

Q: FBXL7 is reported to degrade a broad substrate set (AURKA, survivin/BIRC5, active c-SRC, SNAI1/Snail1, PFKFB4) and behaves as a tumor suppressor or context-dependent oncogenic factor across tissues; which of these substrate axes is dominant in a given cell type, and what determines whether FBXL7 loss is pro- or anti-tumorigenic?

Suggested Experiments

Experiment: Reconstitute SCF(FBXL7)-mediated ubiquitination of AURKA and of survivin/BIRC5 in vitro with purified SKP1, CUL1, RBX1, an E2, and wild-type versus substrate-binding-mutant FBXL7 to map substrate lysine sites and confirm direct, SCF-dependent polyubiquitination.

Experiment: Perform synchronized cell-cycle proteomics and live-cell imaging in FBXL7-knockout versus wild-type cells to quantify AURKA and survivin turnover across mitosis, define FBXL7's centrosomal localization dynamics, and test the apoptotic consequences of substrate stabilization.

Deep Research

Falcon

(FBXL7-deep-research-falcon.md)

Loading supporting content…

Download this section (compressed HTML)

📚 Additional Documentation

Pn Notes

(FBXL7-pn-notes.md)

Loading supporting content…

Download this section (compressed HTML)

📄 View Raw YAML

Loading supporting content…

Download this section (compressed HTML)