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.

p38 MAPK/MK2-mediated induction of miR-34c following DNA damage prevents Myc-dependent DNA replication

“…We and others have shown that Myc levels are controlled by miR-34 (21,26). Although it has been shown previously that levels of Myc are reduced following DNA damage by a number of different mechanisms, including changes in the rate of transcription and protein turnover (27)(28)(29), the possible involvement of miRNAs has not been investigated. It was therefore timely to investigate the role of miR-34c in the control of Myc repression following DNA damage and its importance in this process.…”

Ribosomal Protein L11 Recruits miR-24/miRISC To Repress c-Myc Expression in Response to Ribosomal Stress

“…For this reason, c-Myc should be tightly controlled under stress conditions. Indeed, it has recently been shown that c-Myc levels are reduced in cells following DNA damage (6,7,48). However, whether and how c-Myc is regulated in response to ribosomal stress are not clear.…”

Targeting prostate cancer based on signal transduction and cell cycle pathways

“…Consequently, under normal circumstances these mRNAs are not efficiently translated. 88,89 However, upon Akt-mediated activation of mTOR, these latter mRNAs are highly and disproportionately translated; several key proteins that are overexpressed as a consequence of this event include c-myc, [90][91][92][93][94][95][96] cyclin D1, 97,98 and VEGF 99 among others. 88,89 Cyclin D1 has been reported to be overexpressed in CaP xenografts and metastases, 100,101 while early stage prostatic lesions possess much lower levels of the protein.…”