PARP-1 activation after oxidative insult promotes energy stress-dependent phosphorylation of YAP1 and reduces cell viability.

摘要: Poly(ADP-ribose) Polymerase 1 (PARP-1) is a nuclear enzyme that catalyse the transfer of ADP-ribose units from NAD+ to several target proteins involved in cellular stress responses. Using WRL68 (HeLa derivate) cells, we previously showed PARP-1 activation induced by oxidative after H2O2 treatment lead depletion and ATP, which promoted cell death. In this work, LC-MS/MS based phosphoproteomics cells damage increased phosphorylation YAP1, transcriptional coactivator survival, modified other transcription. Genetic or pharmacological inhibition H2O2-treated reduced YAP1 degradation viability. silencing abrogated protective effect inhibition, indicating important for survival exposed damage. Supplementation also phosphorylation, suggesting loss caused responsible YAP1. Finally, diminished metabolic sensor AMPK. Since, supplementation some AMPK substrates, hypothesized may induce an energy activates summary, new crucial role response viability promoting through mechanism involves NAD+.