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.
Department of Tumor Cell Biology, Sidney Kimmel Cancer Center, San Diego, CA 92121, USA.
YingMeei
Y
Tan
Olle
O
Sangfelt
Charles
C
Spruck
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