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EMBO Rep. 2009 Mar;10(3):271-7. doi: 10.1038/embor.2008.255. Epub 2009 Feb 6.

The M-type receptor PLA2R regulates senescence through the p53 pathway.

Author information

1
UMR 8161, Institut de Biologie de Lille, CNRS/Universités de Lille 1 et 2/Institut Pasteur de Lille, IFR 142, 59021 Lille, France.

Abstract

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.

PMID:
19197340
PMCID:
PMC2658567
DOI:
10.1038/embor.2008.255
[Indexed for MEDLINE]
Free PMC Article

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