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- Title
Multiple cell-type-specific elements regulate Myc protein stability.
- Authors
Herbst, Andreas; Salghetti, Simone E.; So Young Kim; Tansey, William P.
- 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.
- Subjects
MYC proteins; UBIQUITIN; TRANSCRIPTION factors; PROTEOLYSIS; PROTEINS; CELLS
- Publication
Oncogene, 2004, Vol 23, Issue 21, p3863
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1207492