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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2010-6-16
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pubmed:abstractText |
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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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1549-5477
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
24
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1236-41
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pubmed:dateRevised |
2010-12-16
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pubmed:meshHeading |
pubmed-meshheading:20551172-Cell Line, Tumor,
pubmed-meshheading:20551172-Cullin Proteins,
pubmed-meshheading:20551172-DNA-Binding Proteins,
pubmed-meshheading:20551172-Down-Regulation,
pubmed-meshheading:20551172-HeLa Cells,
pubmed-meshheading:20551172-Humans,
pubmed-meshheading:20551172-Multiprotein Complexes,
pubmed-meshheading:20551172-Neoplasms,
pubmed-meshheading:20551172-Protein Stability,
pubmed-meshheading:20551172-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:20551172-Sequence Deletion,
pubmed-meshheading:20551172-TRPC Cation Channels,
pubmed-meshheading:20551172-Ubiquitin-Protein Ligases
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pubmed:year |
2010
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pubmed:articleTitle |
Myc protein is stabilized by suppression of a novel E3 ligase complex in cancer cells.
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pubmed:affiliation |
Department of Genetics, Dartmouth Medical School, Norris Cotton Cancer Center, Lebanon, New Hampshire 03756, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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