title: c-MYC protein is degraded in response to UV irradiation.
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.
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, CNRS-Université de Toulouse, Toulouse, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Britton
authors.forename: Bernard
authors.initials: B
authors.lastname: Salles
authors.forename: Patrick
authors.initials: P
authors.lastname: Calsou
mesh_terms: D000818:Animals; D002460:Cell Line; D042822:Genomic Instability / Q000502:physiology / Q000528:radiation effects; D006801:Humans; D051379:Mice; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc