c-MYC protein is degraded in response to UV irradiation

Cell Cycle. 2008 Jan 1;7(1):63-70. doi: 10.4161/cc.7.1.5111. Epub 2007 Oct 2.

Abstract

The c-MYC proto-oncogene encodes a transcription factor that is critical for cell growth and proliferation. It is one of the genes frequently altered in cancer cells in which it exhibits constitutive activity. The half-life of c-MYC is very short in quiescent cells due to ubiquitin-mediated proteolysis. We report here the rapid and dose-dependent decline of c-MYC protein level after UV-irradiation in various human and rodent cells. This decline is due to a proteasomal degradation of c-MYC protein and does not require the binding sites for the FBW7 and SKP2 ubiquitin ligases. Together, our data exclude a prominent role for the stress-responsive kinase PAK2, for the major phosphoinositide 3-kinase related protein kinases ATR, ATM, DNA-PK and mTOR and for ERK, JNK and p38 mitogen activated protein kinases in this UV-induced degradation process. We propose that c-MYC degradation is part of the global cell response to UV-damage, complementary to the accumulation and activation of the p53 transcription factor. By contributing to the replication arrest after infliction of lesions to the genome, the induced degradation of c-MYC may be part of the safeguard mechanisms maintaining genome stability.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Genomic Instability / physiology
  • Genomic Instability / radiation effects
  • Humans
  • Mice
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Proto-Oncogene Proteins c-myc / radiation effects*
  • Ultraviolet Rays / adverse effects*

Substances

  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-myc