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Cancer Lett. 2008 Nov 18;271(1):1-12. doi: 10.1016/j.canlet.2008.04.036. Epub 2008 Jun 9.

The Fbxw7/hCdc4 tumor suppressor in human cancer.

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Department of Tumor Cell Biology, Sidney Kimmel Cancer Center, San Diego, CA 92121, USA.


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.

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