Multiple cell-type-specific elements regulate Myc protein stability.

Published

Journal Article

Myc is a highly unstable transcription factor that is destroyed by ubiquitin (Ub)-mediated proteolysis. We have previously identified an amino-terminal 'degron' within Myc that signals its destruction; this degron spans the transcriptional activation domain of Myc, and includes two highly conserved regions called Myc boxes I and II. We now report the identification of a second element--the D-element--which is also required for Myc proteolysis. The centrally located D-element is distinct from the PEST domain in Myc, but includes Myc box III, a third highly conserved region with no previously known function. We show that deletion of the D-element stabilizes the Myc protein without affecting its ubiquitylation, and report that the D-element and the degron act in a cell-type-specific manner to direct Myc proteolysis. These data thus demonstrate that Myc stability is regulated at both the ubiquitylation and postubiquitylation levels, and reveal that substrates of the Ub-proteasome system can be targeted for destruction differently in different cell types.

Full Text

Duke Authors

Cited Authors

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

Published Date

  • May 6, 2004

Published In

Volume / Issue

  • 23 / 21

Start / End Page

  • 3863 - 3871

PubMed ID

  • 15021906

Pubmed Central ID

  • 15021906

International Standard Serial Number (ISSN)

  • 0950-9232

Digital Object Identifier (DOI)

  • 10.1038/sj.onc.1207492

Language

  • eng

Conference Location

  • England