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Genes Dev. 2010 Jun 15;24(12):1236-41. doi: 10.1101/gad.1920310.

Myc protein is stabilized by suppression of a novel E3 ligase complex in cancer cells.

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  • 1Department of Genetics, Dartmouth Medical School, Norris Cotton Cancer Center, Lebanon, New Hampshire 03756, USA.

Abstract

Rapid Myc protein turnover is critical for maintaining basal levels of Myc activity in normal cells and a prompt response to changing growth signals. We characterize a new Myc-interacting factor, TRPC4AP (transient receptor potential cation channel, subfamily C, member 4-associated protein)/TRUSS (tumor necrosis factor receptor-associated ubiquitous scaffolding and signaling protein), which is the receptor for a DDB1 (damage-specific DNA-binding protein 1)-CUL4 (Cullin 4) E3 ligase complex for selective Myc degradation through the proteasome. TRPC4AP/TRUSS binds specifically to the Myc C terminus and promotes its ubiquitination and destruction through the recognition of evolutionarily conserved domains in the Myc N terminus. TRPC4AP/TRUSS suppresses Myc-mediated transactivation and transformation in a dose-dependent manner. Finally, we found that TRPC4AP/TRUSS expression is strongly down-regulated in most cancer cell lines, leading to Myc protein stabilization. These studies identify a novel pathway targeting Myc degradation that is suppressed in cancer cells.

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PMID:
20551172
[PubMed - indexed for MEDLINE]
PMCID:
PMC2885659
Free PMC Article
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