Linked Life Data

20818388

Source:http://linkedlifedata.com/resource/pubmed/id/20818388

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2010-10-4
pubmed:abstractText
Mammalian ageing is accompanied by accumulation of genomic DNA damage and progressive decline in the ability of tissues to regenerate. DNA damage activates the tumour suppressor p53, which leads to cell-cycle arrest, senescence or apoptosis. The stability and activity of p53 are induced by DNA damage through posttranslational modifications such as phosphorylation of Thr 21 and Ser 23 (refs 2, 3, 4, 5). To investigate the roles of DNA damage and p53 in tissue-regenerative capability, two phosphorylation-site mutations (T21D and S23D) were introduced into the endogenous p53 gene in mice, so that the synthesized protein mimics phosphorylated p53. The knock-in mice exhibit constitutive p53 activation and segmental progeria that is correlated with the depletion of adult stem cells in multiple tissues, including bone marrow, brain and testes. Furthermore, a deficiency of Puma, which is required for p53-dependent apoptosis after DNA damage, rescues segmental progeria and prevents the depletion of adult stem cells. These findings suggest a key role of p53-dependent apoptosis in depleting adult stem cells after the accumulation of DNA damage, which leads to a decrease in tissue regeneration.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1476-4679
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
993-8
pubmed:dateRevised
2011-11-8
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Puma is required for p53-induced depletion of adult stem cells.
pubmed:affiliation
Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0322, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural