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Cancer Cell. 2014 Oct 13;26(4):455-64. doi: 10.1016/j.ccell.2014.09.013.

Tumor suppression by the Fbw7 ubiquitin ligase: mechanisms and opportunities.

Author information

1
Clinical Research and Human Biology Divisions, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
2
Clinical Research and Human Biology Divisions, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
3
Clinical Research and Human Biology Divisions, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Electronic address: bclurman@fhcrc.org.

Abstract

Tumor suppressors with widespread impact on carcinogenesis control broad spectra of oncogenic pathways. Protein degradation is an emerging mechanism by which tumor suppressors regulate a diversity of pathways and is exemplified by the SCF(Fbw7) ubiquitin ligase. Rapidly accumulating data indicate that SCF(Fbw7) regulates a network of crucial oncoproteins. Importantly, the FBXW7 gene, which encodes Fbw7, is one of the most frequently mutated genes in human cancers. These studies are yielding important new insights into tumorigenesis and may soon enable therapies targeting the Fbw7 pathway. Here, we focus on the mechanisms and consequences of Fbw7 deregulation in cancers and discuss possible therapeutic approaches.

PMID:
25314076
PMCID:
PMC4227608
DOI:
10.1016/j.ccell.2014.09.013
[Indexed for MEDLINE]
Free PMC Article
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