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+.
Skip Nav Destination
Article navigation
December 2020
-
Cover Image
Cover Image
The cover image shows a word cloud based on the findings of the review article by Fulcher and Sapkota (pp. 4397–4423) in this issue, depicting the many biological functions and modes of regulation of the CK1 family of Ser/Thr protein kinases. Image created by Luke Fulcher.
Research Article|
December 03 2020
PARP-1 activation after oxidative insult promotes energy stress-dependent phosphorylation of YAP1 and reduces cell viability
Sandra M. Martín-Guerrero;
1Departamento de Biología Celular, Facultad de Ciencias, Universidad de Granada, Spain
Correspondence: Sandra Maria Martín-Guerrero (sandra.martin_guerrero@kcl.ac.uk)
Search for other works by this author on:
Pedro Casado
;
Pedro Casado
Data curation, Formal analysis, Methodology, Writing - review & editing
2Signalling and Proteomics Group, Centre for Genomics and Computational Biology, Barts Cancer Institute, Queen Mary University of London, London, U.K.
Search for other works by this author on:
Maruan Hijazi;
Maruan Hijazi
Formal analysis, Methodology, Writing - review & editing
2Signalling and Proteomics Group, Centre for Genomics and Computational Biology, Barts Cancer Institute, Queen Mary University of London, London, U.K.
Search for other works by this author on:
Vinothini Rajeeve;
Vinothini Rajeeve
Data curation, Methodology
2Signalling and Proteomics Group, Centre for Genomics and Computational Biology, Barts Cancer Institute, Queen Mary University of London, London, U.K.
Search for other works by this author on:
Julio Plaza-Díaz;
Julio Plaza-Díaz
3Departamento de Bioquímica y Biología Molecular II, Facultad de Farmacia, Universidad de Granada, Granada, Spain
4Department of Pediatrics, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Canada
Search for other works by this author on:
Francisco Abadía-Molina;
Francisco Abadía-Molina
1Departamento de Biología Celular, Facultad de Ciencias, Universidad de Granada, Spain
5Instituto de Nutrición y Tecnología de los Alimentos ‘José Mataix’, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain
Search for other works by this author on:
Julio Navascués;
Julio Navascués
1Departamento de Biología Celular, Facultad de Ciencias, Universidad de Granada, Spain
Search for other works by this author on:
Miguel A. Cuadros;
Miguel A. Cuadros
Conceptualization, Writing - original draft, Writing - review & editing
1Departamento de Biología Celular, Facultad de Ciencias, Universidad de Granada, Spain
Search for other works by this author on:
Pedro R. Cutillas;
Pedro R. Cutillas
Resources, Data curation, Software, Formal analysis, Funding acquisition, Methodology
2Signalling and Proteomics Group, Centre for Genomics and Computational Biology, Barts Cancer Institute, Queen Mary University of London, London, U.K.
Search for other works by this author on:
David Martín-Oliva
David Martín-Oliva
1Departamento de Biología Celular, Facultad de Ciencias, Universidad de Granada, Spain
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
June 29 2020
Revision Received:
October 26 2020
Accepted:
November 04 2020
Accepted Manuscript online:
November 04 2020
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2020
Biochem J (2020) 477 (23): 4491–4513.
Article history
Received:
June 29 2020
Revision Received:
October 26 2020
Accepted:
November 04 2020
Accepted Manuscript online:
November 04 2020
Citation
Sandra M. Martín-Guerrero, Pedro Casado, Maruan Hijazi, Vinothini Rajeeve, Julio Plaza-Díaz, Francisco Abadía-Molina, Julio Navascués, Miguel A. Cuadros, Pedro R. Cutillas, David Martín-Oliva; PARP-1 activation after oxidative insult promotes energy stress-dependent phosphorylation of YAP1 and reduces cell viability. Biochem J 11 December 2020; 477 (23): 4491–4513. doi: https://doi.org/10.1042/BCJ20200525
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.