Multiple cell-type-specific elements regulate Myc protein stability

Herbst, A., Salghetti, S. E., Kim, S. Y., Tansey, W. P. (May 2004) Multiple cell-type-specific elements regulate Myc protein stability. Oncogene, 23 (21). pp. 3863-71. ISSN 0950-9232 (Print)

URL: http://www.nature.com/onc/journal/v23/n21/full/120...
DOI: 10.1038/sj.onc.1207492

Abstract

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.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Sequence Animals Conserved Sequence Cysteine Endopeptidases physiology Humans Molecular Sequence Data Multienzyme Complexes physiology Proteasome Endopeptidase Complex Proto-Oncogene Proteins c-myc chemistry metabolism Rats Ubiquitin metabolism
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > ubiquitin ligase
CSHL Authors:
Depositing User: CSHL Librarian
Date: 6 May 2004
Date Deposited: 01 Feb 2012 18:33
Last Modified: 01 Feb 2012 18:33
URI: http://repository.cshl.edu/id/eprint/22386

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