Destruction of Myc by ubiquitin-mediated proteolysis: cancer-associated and transforming mutations stabilize Myc

Salghetti, S. E., Kim, S. Y., Tansey, W. P. (1999) Destruction of Myc by ubiquitin-mediated proteolysis: cancer-associated and transforming mutations stabilize Myc. Embo Journal, 18 (3). pp. 717-26. ISSN 0261-4189 (Print)

URL: http://www.ncbi.nlm.nih.gov/pubmed/9927431
DOI: 10.1093/emboj/18.3.717

Abstract

The human proto-oncogene c-myc encodes a highly unstable transcription factor that promotes cell proliferation. Although the extreme instability of Myc plays an important role in preventing its accumulation in normal cells, little is known about how Myc is targeted for rapid destruction. Here, we have investigated mechanisms regulating the stability of Myc. We show that Myc is destroyed by ubiquitin-mediated proteolysis, and define two elements in Myc that oppositely regulate its stability: a transcriptional activation domain that promotes Myc destruction, and a region required for association with the POZ domain protein Miz-1 that stabilizes Myc. We also show that Myc is stabilized by cancer-associated and transforming mutations within its transcriptional activation domain. Our data reveal a complex network of interactions regulating Myc destruction, and imply that enhanced protein stability contributes to oncogenic transformation by mutant Myc proteins.

Item Type: Paper
Uncontrolled Keywords: Animals Cell Line Cell Transformation, Neoplastic DNA-Binding Proteins/metabolism Drug Stability Endopeptidases/metabolism Genes, myc Humans Mice Mutation Neoplasms/ genetics/ metabolism Proto-Oncogene Proteins c-myc/ genetics/ metabolism Recombinant Proteins/genetics/metabolism Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Saccharomyces cerevisiae/genetics/metabolism Transcription Factors Ubiquitins/ metabolism
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > Myc
diseases & disorders > neoplasms
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > proteolysis
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
CSHL Authors:
Communities: CSHL labs > Tansey lab
Depositing User: Kathleen Darby
Date Deposited: 30 Apr 2014 15:37
Last Modified: 30 Apr 2014 15:37
PMCID: PMC1171164
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29790

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