Journal
CANCER LETTERS
Volume 271, Issue 1, Pages 1-12Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2008.04.036
Keywords
Fbxw7; Ubiquitin ligase; Tumor suppressor; Cyclin E1; c-Myc
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Funding
- American Cancer Society
- Swedish Research Council
- Swedish Cancer Society
- Swedish Children Foundation
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Fbxw7/hCdc4 is a member of the F-box family of proteins, which function as interchangeable substrate recognition components of the SCF ubiquitin ligases. SCFFbxw7/hCdc4 targets several important oncoproteins including c-Myc, c-Jun, cyclin El, 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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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