jeudi 12 avril 2012

Mutated genes in cancer (63) – FBXW7


In databases:

● Entrez ( 55294 or FBXW7
● Ensembl ( ENSG00000109670
● UniProt ( Q969H0
● GeneCards ( FBXW7
● HGNC ( 16712 or FBXW7

Gene locus:


Protein name:

F-box and WD repeat domain containing 7

Protein Size:

707 amino acids; about 80 kDa


FBXW7 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. This protein binds directly to cyclin E and probably targets cyclin E for ubiquitin-mediated degradation.

Cancer-related alterations:

Somatic mutations, consisting mostly in substitutions, have been observed in tumors of  biliary tract, endometrium, haematopoietic and lymphoid tissue, large intestine, thyroid, stomach, cervix. Mutations have also been described in ovarian and breast cancer cell lines. Mutations are present throughout the gene, but hot spots are found at amino acids 465, 479 and 505.

References (open access):

The Fbw7/human CDC4 tumor suppressor targets proproliferative factor KLF5 for ubiquitination and degradation through multiple phosphodegron motifs. Liu N, Li H, Li S, Shen M, Xiao N, Chen Y, Wang Y, Wang W, Wang R, Wang Q, Sun J, Wang P. J Biol Chem. 2010 Jun 11;285(24):18858-67.

The Fbw7 tumor suppressor targets KLF5 for ubiquitin-mediated degradation and suppresses breast cell proliferation. Zhao D, Zheng HQ, Zhou Z, Chen C. Cancer Res. 2010 Jun 1;70(11):4728-38.

Prognostic implications of NOTCH1 and FBXW7 mutations in adult acute T-lymphoblastic leukemia. Baldus CD, Thibaut J, Goekbuget N, Stroux A, Schlee C, Mossner M, Burmeister T, Schwartz S, Bloomfield CD, Hoelzer D, Thiel E, Hofmann WK. Haematologica. 2009 Oct;94(10):1383-90.

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