FBXW7

From Wikipedia, the free encyclopedia
  (Redirected from FBXW7 (gene))
Jump to navigation Jump to search
FBXW7
Protein FBXW7 PDB 2ovp.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesFBXW7, AGO, CDC4, FBW6, FBW7, FBX30, FBXO30, FBXW6, SEL-10, SEL10, hAgo, hCdc4, F-box and WD repeat domain containing 7
External IDsMGI: 1354695 HomoloGene: 117451 GeneCards: FBXW7
Gene location (Human)
Chromosome 4 (human)
Chr.Chromosome 4 (human)[1]
Chromosome 4 (human)
Genomic location for FBXW7
Genomic location for FBXW7
Band4q31.3Start152,320,544 bp[1]
End152,536,063 bp[1]
RNA expression pattern
PBB GE FBXW7 218751 s at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001013415
NM_001257069
NM_018315
NM_033632
NM_001349798

NM_001177773
NM_001177774
NM_080428

RefSeq (protein)

NP_001013433
NP_001243998
NP_060785
NP_361014
NP_001336727

NP_001171244
NP_001171245
NP_536353

Location (UCSC)Chr 4: 152.32 – 152.54 MbChr 3: 84.82 – 84.98 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

F-box/WD repeat-containing protein 7 is a protein that in humans is encoded by the FBXW7 gene.[5][6][7]

Function[edit]

This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene was previously referred to as FBX30, and belongs to the Fbws class; in addition to an F-box, this protein contains 7 tandem WD40 repeats. This protein binds directly to cyclin E and probably targets cyclin E for ubiquitin-mediated degradation. Other well established pro-proliferative targets of FBXW7 are c-Myc and Notch1. Mono-allelic mutations in this gene are detected in sporadic cancers [e.g., cholangiocarcinoma (35%), T-ALL (31%), endometrial carcinoma (16%), colorectal carcinoma (16%), bladder cancer (10%), gastric carcinoma (6%), lung squamous cell carcinoma (5%), etc.]. These findings implicate the gene's potential role in the pathogenesis of human cancers. Despite being commonly acknowledged as a haploinsufficient tumor suppressor, mutations are not found in some cancers, such as acute myeloid leukemia and multiple myeloma. One possibility is that FBXW7 substrate stabilization is detrimental in these neoplasms. For example, the FBXW7 substrate C/EBPα suppresses AML[8] and multiple myelomas require constitutive NF-κB signaling; therefore, disruption of FBXW7-mediated ubiquitylation of IκBd in these tumors results in cell death.[9][10]

Three transcript variants encoding three different isoforms have been found for this gene.[7]

Interactions[edit]

FBXW7 has been shown to interact with:

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000109670 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028086 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ Winston JT, Koepp DM, Zhu C, Elledge SJ, Harper JW (Dec 1999). "A family of mammalian F-box proteins". Curr Biol. 9 (20): 1180–2. doi:10.1016/S0960-9822(00)80021-4. PMID 10531037.
  6. ^ Gupta-Rossi N, Le Bail O, Gonen H, Brou C, Logeat F, Six E, Ciechanover A, Israël A (Sep 2001). "Functional interaction between SEL-10, an F-box protein, and the nuclear form of activated Notch1 receptor". J Biol Chem. 276 (37): 34371–8. doi:10.1074/jbc.M101343200. PMID 11425854.
  7. ^ a b "Entrez Gene: FBXW7 F-box and WD repeat domain containing 7".
  8. ^ Bengoechea-Alonso MT, Ericsson J (June 2010). "The ubiquitin ligase Fbxw7 controls adipocyte differentiation by targeting C/EBPalpha for degradation". Proceedings of the National Academy of Sciences of the United States of America. 107 (26): 11817–22. doi:10.1073/pnas.0913367107. PMC 2900639. PMID 20534483.
  9. ^ Busino L, Millman SE, Scotto L, Kyratsous CA, Basrur V, O'Connor O, Hoffmann A, Elenitoba-Johnson KS, Pagano M (March 2012). "Fbxw7α- and GSK3-mediated degradation of p100 is a pro-survival mechanism in multiple myeloma". Nature Cell Biology. 14 (4): 375–85. PMC 3339029. PMID 22388891.
  10. ^ Busino L, Millman SE, Pagano M (December 2012). "SCF-mediated degradation of p100 (NF-κB2): mechanisms and relevance in multiple myeloma". Science Signaling. 5 (253): pt14. doi:10.1126/scisignal.2003408. PMC 3871187. PMID 23211527.
  11. ^ Kanei-Ishii C, Nomura T, Takagi T, Watanabe N, Nakayama KI, Ishii S (Nov 2008). "Fbxw7 acts as an E3 ubiquitin ligase that targets c-Myb for nemo-like kinase (NLK)-induced degradation". J. Biol. Chem. 283 (45): 30540–8. doi:10.1074/jbc.M804340200. PMC 2662147. PMID 18765672.
  12. ^ Olson BL, Hock MB, Ekholm-Reed S, Wohlschlegel JA, Dev KK, Kralli A, Reed SI (Jan 2008). "SCFCdc4 acts antagonistically to the PGC-1alpha transcriptional coactivator by targeting it for ubiquitin-mediated proteolysis". Genes Dev. 22 (2): 252–64. doi:10.1101/gad.1624208. PMC 2192758. PMID 18198341.
  13. ^ a b Staropoli JF, McDermott C, Martinat C, Schulman B, Demireva E, Abeliovich A (Mar 2003). "Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity". Neuron. 37 (5): 735–49. doi:10.1016/s0896-6273(03)00084-9. PMID 12628165.
  14. ^ Wu G, Lyapina S, Das I, Li J, Gurney M, Pauley A, Chui I, Deshaies RJ, Kitajewski J (Nov 2001). "SEL-10 is an inhibitor of notch signaling that targets notch for ubiquitin-mediated protein degradation". Mol. Cell. Biol. 21 (21): 7403–15. doi:10.1128/MCB.21.21.7403-7415.2001. PMC 99913. PMID 11585921.

Further reading[edit]