Journal
EMBO REPORTS
Volume 10, Issue 3, Pages 271-277Publisher
WILEY
DOI: 10.1038/embor.2008.255
Keywords
senescence; PLA2R; p53
Categories
Funding
- Association pour la Recherche sur le Cancer
- Comite du Pas de Calais de la Ligue Nationale contre le Cancer
- MRC [MC_U120085810] Funding Source: UKRI
- Medical Research Council [MC_U120085810] Funding Source: researchfish
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Senescence is a stable proliferative arrest induced by various stresses such as telomere erosion, oncogenic or oxidative stress. Compelling evidence suggests that it acts as a barrier against tumour development. Describing new mechanisms that favour an escape from senescence can thus reveal new insights into tumorigenesis. To identify new genes controlling the senescence programme, we performed a loss-of-function genetic screen in primary human fibroblasts. We report that knockdown of the M-type receptor PLA2R ( phospholipase A2 receptor) prevents the onset of replicative senescence and diminishes stress-induced senescence. Interestingly, expression of PLA2R increases during replicative senescence, and its ectopic expression results in premature senescence. We show that PLA2R regulates senescence in a reactive oxygen species-DNA damage-p53-dependent manner. Taken together, our study identifies PLA2R as a potential new tumour suppressor gene crucial in the induction of cellular senescence through the activation of the p53 pathway.
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