@misc{10481/97911,
year = {2020},
month = {12},
url = {https://hdl.handle.net/10481/97911},
abstract = {Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear enzyme that catalyze 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 that PARP-1 activation induced by oxidative stress after H2O2 treatment lead to depletion of cellular NAD+ and ATP, which promoted cell death. In this work, LC–MS/MS-based phosphoproteomics in WRL68 cells showed that the oxidative damage induced by H2O2 increased the phosphorylation of YAP1, a transcriptional co-activator involved in cell survival, and modified the phosphorylation of other proteins involved in transcription. Genetic or pharmacological inhibition of PARP-1 in H2O2-treated cells reduced YAP1 phosphorylation and degradation and increased cell viability. YAP1 silencing abrogated the protective effect of PARP-1 inhibition, indicating that YAP1 is important for the survival of WRL68 cells exposed to oxidative damage. Supplementation of NAD+ also reduced YAP1 phosphorylation, suggesting that the loss of cellular NAD+ caused by PARP-1 activation after oxidative treatment is responsible for the phosphorylation of YAP1. Finally, PARP-1 silencing after oxidative treatment diminished the activation of the metabolic sensor AMPK. Since NAD+ supplementation reduced the phosphorylation of some AMPK substrates, we hypothesized that the loss of cellular NAD+ after PARP-1 activation may induce an energy stress that activates AMPK. In summary, we showed a new crucial role of PARP-1 in the response to oxidative stress in which PARP-1 activation reduced cell viability by promoting the phosphorylation and degradation of YAP1 through a mechanism that involves the depletion of NAD+.},
organization = {Ministerio de Educación, Cultura y Deporte (FPU14/02219, EST16/00301 and EST17/00231), Programa Operativo FEDER de Andalucía 2014-2020 (B-CTS-185-UGR18), London Charity (MIMG1M3R) and Cancer Research UK (C16420/A18066).},
publisher = {Portland Press},
keywords = {LC–MS/MS},
keywords = {PARP-1},
keywords = {YAP1},
keywords = {cell survival},
keywords = {phosphorylation.},
title = {PARP-1 activation after oxidative insult promotes energy stress-dependent phosphorylation of YAP1 and reduces cell viability},
doi = {10.1042/BCJ20200525},
author = {Martín-Guerrero, Sandra María and Casado, Pedro and Hijazi, Maruan and Rajeeve, Vinothini and Plaza-Díaz, Julio and Abadía-Molina, Francisco and Navascués, Julio and Cuadros, Miguel Ángel and R Cutillas, Pedro and Martín-Oliva, David},
}