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

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.

journal_name

EMBO Rep

journal_title

EMBO reports

authors

Augert A,Payré C,de Launoit Y,Gil J,Lambeau G,Bernard D

doi

10.1038/embor.2008.255

subject

Has Abstract

pub_date

2009-03-01 00:00:00

pages

271-7

issue

3

eissn

1469-221X

issn

1469-3178

pii

embor2008255

journal_volume

10

pub_type

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