Multiple cell-type-specific elements regulate Myc protein stability

Oncogene. 2004 May 6;23(21):3863-71. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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*
  • Proto-Oncogene Proteins c-myc / metabolism
  • Rats
  • Ubiquitin / metabolism


  • Multienzyme Complexes
  • Proto-Oncogene Proteins c-myc
  • Ubiquitin
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex