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Article: Accelerated ageing in mice deficient in Zmpste24 protease is linked to p53 signalling activation

TitleAccelerated ageing in mice deficient in Zmpste24 protease is linked to p53 signalling activation
Authors
Issue Date2005
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/nature
Citation
Nature, 2005, v. 437 n. 7058, p. 564-568 How to Cite?
AbstractZmpste24 (also called FACE-1) is a metalloproteinase involved in the maturation of lamin A (Lmna), an essential component of the nuclear envelope. Both Zmpste24- and Lmna-deficient mice exhibit profound nuclear architecture abnormalities and multiple histopathological defects that phenocopy an accelerated ageing process. Similarly, diverse human progeroid syndromes are caused by mutations in ZMPSTE24 or LMNA genes. To elucidate the molecular mechanisms underlying these devastating diseases, we have analysed the transcriptional alterations occurring in tissues from Zmpste24-deficient mice. We demonstrate that Zmpste24 deficiency elicits a stress signalling pathway that is evidenced by a marked upregulation of p53 target genes, and accompanied by a senescence phenotype at the cellular level and accelerated ageing at the organismal level. These phenotypes are largely rescued in Zmpste24 -/-Lmna +/- mice and partially reversed in Zmpste24 -/-p53 -/- mice. These findings provide evidence for the existence of a checkpoint response activated by the nuclear abnormalities caused by prelamin A accumulation, and support the concept that hyperactivation of the tumour suppressor p53 may cause accelerated ageing. © 2005 Nature Publishing Group.
Persistent Identifierhttp://hdl.handle.net/10722/147524
ISSN
2015 Impact Factor: 38.138
2015 SCImago Journal Rankings: 21.936
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorVarela, Ien_US
dc.contributor.authorCadiñanos, Jen_US
dc.contributor.authorPendás, AMen_US
dc.contributor.authorGutiérrezFernández, Aen_US
dc.contributor.authorFolgueras, ARen_US
dc.contributor.authorSánchez, LMen_US
dc.contributor.authorZhou, Zen_US
dc.contributor.authorRodríguez, FJen_US
dc.contributor.authorStewart, CLen_US
dc.contributor.authorVega, JAen_US
dc.contributor.authorTryggvason, Ken_US
dc.contributor.authorFreije, JMPen_US
dc.contributor.authorLópezOtín, Cen_US
dc.date.accessioned2012-05-29T06:04:21Z-
dc.date.available2012-05-29T06:04:21Z-
dc.date.issued2005en_US
dc.identifier.citationNature, 2005, v. 437 n. 7058, p. 564-568en_US
dc.identifier.issn0028-0836en_US
dc.identifier.urihttp://hdl.handle.net/10722/147524-
dc.description.abstractZmpste24 (also called FACE-1) is a metalloproteinase involved in the maturation of lamin A (Lmna), an essential component of the nuclear envelope. Both Zmpste24- and Lmna-deficient mice exhibit profound nuclear architecture abnormalities and multiple histopathological defects that phenocopy an accelerated ageing process. Similarly, diverse human progeroid syndromes are caused by mutations in ZMPSTE24 or LMNA genes. To elucidate the molecular mechanisms underlying these devastating diseases, we have analysed the transcriptional alterations occurring in tissues from Zmpste24-deficient mice. We demonstrate that Zmpste24 deficiency elicits a stress signalling pathway that is evidenced by a marked upregulation of p53 target genes, and accompanied by a senescence phenotype at the cellular level and accelerated ageing at the organismal level. These phenotypes are largely rescued in Zmpste24 -/-Lmna +/- mice and partially reversed in Zmpste24 -/-p53 -/- mice. These findings provide evidence for the existence of a checkpoint response activated by the nuclear abnormalities caused by prelamin A accumulation, and support the concept that hyperactivation of the tumour suppressor p53 may cause accelerated ageing. © 2005 Nature Publishing Group.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/natureen_US
dc.relation.ispartofNatureen_US
dc.titleAccelerated ageing in mice deficient in Zmpste24 protease is linked to p53 signalling activationen_US
dc.typeArticleen_US
dc.identifier.emailZhou, Z:zhongjun@hkucc.hku.hken_US
dc.identifier.authorityZhou, Z=rp00503en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/nature04019en_US
dc.identifier.scopuseid_2-s2.0-25644440744en_US
dc.identifier.hkuros116555-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-25644440744&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume437en_US
dc.identifier.issue7058en_US
dc.identifier.spage564en_US
dc.identifier.epage568en_US
dc.identifier.isiWOS:000232004800053-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.f10001028706-
dc.identifier.scopusauthoridVarela, I=10144525100en_US
dc.identifier.scopusauthoridCadiñanos, J=6506257822en_US
dc.identifier.scopusauthoridPendás, AM=35595485200en_US
dc.identifier.scopusauthoridGutiérrezFernández, A=9234544800en_US
dc.identifier.scopusauthoridFolgueras, AR=9234544900en_US
dc.identifier.scopusauthoridSánchez, LM=7202051274en_US
dc.identifier.scopusauthoridZhou, Z=8631856300en_US
dc.identifier.scopusauthoridRodríguez, FJ=7402203048en_US
dc.identifier.scopusauthoridStewart, CL=7401937591en_US
dc.identifier.scopusauthoridVega, JA=7201630414en_US
dc.identifier.scopusauthoridTryggvason, K=7102025185en_US
dc.identifier.scopusauthoridFreije, JMP=7005118867en_US
dc.identifier.scopusauthoridLópezOtín, C=7102600806en_US
dc.identifier.citeulike272373-

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