The Fbxw7/hCdc4 tumor suppressor in human cancer.
Fbxw7/hCdc4 is a member of the F-box family of proteins, which function as interchangeable substrate recognition components of the SCF ubiquitin ligases. SCF(Fbxw7/hCdc4) targets several important oncoproteins including c-Myc, c-Jun, cyclin E1, and Notch, for ubiquitin-dependent proteolysis. Recent studies have shown that FBXW7/hCDC4 is mutated in a variety of human tumor types, suggesting that it is a general tumor suppressor in human cancer. Alteration of Fbxw7/hCdc4 function is linked to defects in differentiation, cellular proliferation, and genetic instability. In this review, we summarize what is known about Fbxw7/hCdc4-mediated degradation in the regulation of cellular proliferation and discuss how alteration of its function contributes to human tumorigenesis.
Tan
YingMeei
Y
Department of Tumor Cell Biology, Sidney Kimmel Cancer Center, San Diego, CA 92121, USA.
Sangfelt
Olle
O
Spruck
Charles
C
D018797:Cell Cycle Proteins / Q000235:genetics*; D044783:F-Box Proteins / Q000235:genetics*; D000073979:F-Box-WD Repeat-Containing Protein 7; D016147:Genes, Tumor Suppressor; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D044767:Ubiquitin-Protein Ligases