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

Herbst A, Salghetti SE, Kim SY, Tansey WP
Oncogene. 2004 23 (21): 3863-71

PMID: 15021906 · DOI:10.1038/sj.onc.1207492

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.

MeSH Terms (11)

Amino Acid Sequence Animals Conserved Sequence Cysteine Endopeptidases Humans Molecular Sequence Data Multienzyme Complexes Proteasome Endopeptidase Complex Proto-Oncogene Proteins c-myc Rats Ubiquitin

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