PXD019823 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | PARP-1 activation after oxidative insult promotes energy stress-dependent phosphorylation of YAP1 and reduces cell viability |
Description | 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 the cell line WRL68, we have previously shown that the activation of PARP-1 induced by oxidative stress after H2O2 treatment lead to depletion of cellular NAD+ and ATP, which promote cell death. In this work, we used LC-MS/MS based phosphoproteomics to show that the oxidative damage induced by H2O2 treatment modified the phosphorylation of several proteins in WRL68 cells, most of them related to transcription process. Interestingly, genetic or pharmacological inhibition of PARP-1 reduced the phosphorylation of YAP1, a transcriptional coactivator involved in cell survival, in WRL68 cells after H2O2 treatment. Inhibition of PARP-1 increased cell viability after oxidative treatment and diminished the degradation of YAP1; the elimination of YAP1 by gene silencing abrogated the protective effect of PARP-1 inhibition, indicating that YAP1 is important for the survival of WRL68 cells after oxidative damage. In the same way, the supplementation of NAD+, substrate of PARP-1, on WRL68 cells suffering oxidative damage reduced the phosphorylation of YAP1, 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 AMPK, a master regulator of cell metabolism implicated in the restoration of energy balance during metabolic stress. Since NAD+ supplementation reduced the phosphorylation of some AMPK substrates in WRL68 cells after oxidative treatment, we hypothesize that the loss of cellular NAD+ after PARP-1 activation may induce a metabolic stress that activates AMPK. In summary, we showed a new crucial role of PARP-1 in the response to oxidative stress in WRL68 cells; PARP-1 activation reduces the cell viability by promoting the phosphorylation and degradation of YAP1, which is mediated by the energy stress caused by PARP-1 activation. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_05:16:55.085.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD019823 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Pedro Casado-Izquierdo |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-06-16 23:15:58 | ID requested | |
1 | 2020-12-17 23:19:43 | announced | |
⏵ 2 | 2024-10-22 05:16:55 | announced | 2024-10-22: Updated project metadata. |
Publication List
10.1042/bcj20200525; |
10.6019/PXD019823; |
Mart, í, n-Guerrero SM, Casado P, Hijazi M, Rajeeve V, Plaza-D, í, az J, Abad, í, a-Molina F, Navascu, é, s J, Cuadros MA, Cutillas PR, Mart, í, n-Oliva D, PARP-1 activation after oxidative insult promotes energy stress-dependent phosphorylation of YAP1 and reduces cell viability. Biochem J, 477(23):4491-4513(2020) [pubmed] |
Keyword List
submitter keyword: YAP1, cell survival, phosphorylation, oxidative stress,PARP-1, energy stress, LC-MS/MS |
Contact List
Pedro R. Cutillas |
contact affiliation | Centre for Genomics and Computational Biology Barts Cancer Institute Queen Mary University of London |
contact email | p.cutillas@qmul.ac.uk |
lab head | |
Pedro Casado-Izquierdo |
contact affiliation | Cell Signalling |
contact email | p.m.casado-izquierdo@qmul.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD019823
- Label: PRIDE project
- Name: PARP-1 activation after oxidative insult promotes energy stress-dependent phosphorylation of YAP1 and reduces cell viability