Ras enhances Myc protein stability

Mol Cell. 1999 Feb;3(2):169-79. doi: 10.1016/s1097-2765(00)80308-1.

Abstract

Various experiments have demonstrated a collaborative action of Myc and Ras, both in normal cell growth control as well as during oncogenesis. We now show that Ras enhances the accumulation of Myc activity by stabilizing the Myc protein. Whereas Myc has a very short half-life when produced in the absence of mitogenic signals, due to degradation by the 26S proteasome, the half-life of Myc increases markedly in growth-stimulated cells. This stabilization is dependent on the Ras/Raf/MAPK pathway and is not augmented by proteasome inhibition, suggesting that Ras inhibits the proteasome-dependent degradation of Myc. We propose that one aspect of Myc-Ras collaboration is an ability of Ras to enhance the accumulation of transcriptionally active Myc protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / physiology
  • Cell Line
  • E2F2 Transcription Factor
  • Enzyme Activation
  • Fibroblasts / metabolism
  • Flavonoids / pharmacology
  • Gene Expression Regulation / physiology
  • Genes, myc
  • Half-Life
  • Mitosis / drug effects
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / physiology
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Proto-Oncogene Proteins c-raf / genetics
  • Proto-Oncogene Proteins c-raf / physiology
  • Proto-Oncogene Proteins p21(ras) / physiology*
  • Recombinant Fusion Proteins / metabolism
  • S Phase
  • Signal Transduction / physiology
  • Transcription Factors / genetics
  • Transcription Factors / physiology
  • Transcription, Genetic
  • Transfection

Substances

  • E2F2 Transcription Factor
  • Flavonoids
  • Proto-Oncogene Proteins c-myc
  • Recombinant Fusion Proteins
  • Transcription Factors
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Proto-Oncogene Proteins p21(ras)
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one