ΔNp63α down-regulates c-Myc modulator MM1 via E3 ligase HERC3 in the regulation of cell senescence.

ABSTRACT: p63 and c-Myc are key transcription factors controlling genes involved in the cell cycle and cellular senescence. We previously reported that p63α can destabilize MM1 protein to derepress c-Myc, resulting in cell cycle progress and tumorigenesis. However, how the proteasomal degradation of MM1 is facilitated remains unclear. In the present study, we identified a novel E3 ligase, HERC3, which can mediate ubiquitination of MM1 and promote its proteasome-dependent degradation. We found that ΔNp63α transcriptionally up-regulates HERC3 and knockdown of HERC3 abrogates ΔNp63α-induced down-regulation of MM1. Either overexpression of MM1 or ablation of HERC3 induces cell senescence, while knockdown of MM1 rescues cell senescence induced by deficiency of either ΔNp63α or HERC3, implicating the invo

SUBMITTER: Chen Y 

PROVIDER: S-EPMC6261956 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature