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Oxidative stress induces an ATM‐independent senescence pathway through p38 MAPK‐mediated lamin B1 accumulation
Author(s) -
Barascu Aurelia,
Le Chalony Catherine,
Pennarun Gaëlle,
Genet Diane,
Imam Naima,
Lopez Bernard,
Bertrand Pascale
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.492
Subject(s) - lamin , senescence , biology , microbiology and biotechnology , telomere , nuclear lamina , dna damage , progeria , ataxia telangiectasia , nuclear protein , oxidative stress , genetics , dna , gene , biochemistry , transcription factor , nucleus
We report crosstalk between three senescence‐inducing conditions, DNA damage response (DDR) defects, oxidative stress (OS) and nuclear shape alterations. The recessive autosomal genetic disorder Ataxia telangiectasia (A‐T) is associated with DDR defects, endogenous OS and premature ageing. Here, we find frequent nuclear shape alterations in A‐T cells, as well as accumulation of the key nuclear architecture component lamin B1. Lamin B1 overexpression is sufficient to induce nuclear shape alterations and senescence in wild‐type cells, and normalizing lamin B1 levels in A‐T cells reciprocally reduces both nuclear shape alterations and senescence. We further show that OS increases lamin B1 levels through p38 Mitogen Activated Protein kinase activation. Lamin B1 accumulation and nuclear shape alterations also occur during stress‐induced senescence and oncogene‐induced senescence (OIS), two canonical senescence situations. These data reveal lamin B1 as a general molecular mediator that controls OS‐induced senescence, independent of established Ataxia Telangiectasia Mutated (ATM) roles in OIS.