Nijmegen breakage syndrome fibroblasts expressing the C-terminal truncated NBNp70 protein undergo p38/MK2-dependent premature senescence

Davis, Terence ORCID: https://orcid.org/0000-0003-2780-0262, Tivey, Hannah S.E., Brook, Amy J.C. and Kipling, David 2015. Nijmegen breakage syndrome fibroblasts expressing the C-terminal truncated NBNp70 protein undergo p38/MK2-dependent premature senescence. Biogerontology 16 (1) , pp. 43-51. 10.1007/s10522-014-9530-3

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Abstract

Fibroblasts from the progeroid Nijmegen breakage syndrome that express a truncated version of the nibrin protein (NBNp70) undergo premature senescence and have an enlarged morphology with high levels of senescence-associated β-galactosidase, although they do not have F-actin stress fibres. Growth of these fibroblasts in the continuous presence of p38 inhibitors resulted in a large increase in replicative capacity and changed the cellular morphology so that the cells resembled young normal fibroblasts. A similar effect was seen using an inhibitor of the p38 downstream effector kinase MK2. These data suggest that NBNp70 expressing cells undergo a degree of stress-induced replicative senescence via p38/MK2 activation, potentially due to increased telomere dysfunction, that may play a role in the progeroid features seen in this syndrome.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Publisher:	Springer
ISSN:	1389-5729
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	3 September 2014
Last Modified:	05 May 2023 07:49
URI:	https://orca.cardiff.ac.uk/id/eprint/78966

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