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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Salghetti, SE; Kim, SY; Tansey, WP

Published Date

  • February 1, 1999

Published In

Volume / Issue

  • 18 / 3

Start / End Page

  • 717 - 726

PubMed ID

  • 9927431

Pubmed Central ID

  • 9927431

International Standard Serial Number (ISSN)

  • 0261-4189

Digital Object Identifier (DOI)

  • 10.1093/emboj/18.3.717

Language

  • eng

Conference Location

  • England