Linked Life Data

11709054

Source:http://linkedlifedata.com/resource/pubmed/id/11709054

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 6
pubmed:dateCreated
2001-11-15
pubmed:abstractText
Cellular stresses, such as growth factor deprivation, DNA damage or oncogene expression, lead to stabilization and activation of the p53 tumour suppressor protein. Depending on the cellular context, this results in one of two different outcomes: cell cycle arrest or apoptotic cell death. Cell death induced through the p53 pathway is executed by the caspase proteinases, which, by cleaving their substrates, lead to the characteristic apoptotic phenotype. Caspase activation by p53 occurs through the release of apoptogenic factors from the mitochondria, including cytochrome c and Smac/DIABLO. Released cytochrome c allows the formation of a high-molecular weight complex, the apoptosome, which consists of the adapter protein Apaf-1 and caspase 9, which is activated following recruitment into the apoptosome. Active caspase 9 then cleaves and activates the effector caspases, such as caspases-3 and -7, which execute the death program. Released Smac/DIABLO facilitates caspase activation through repression of the IAP caspase inhibitor proteins. The release of mitochondrial apoptogenic factors is regulated by the pro- and anti-apoptotic Bcl-2 family proteins, which either induce or prevent the permeabilization of the outer mitochondrial membrane. The mechanism by which p53 signals to the Bcl-2 family proteins is unclear. It was shown that some of the pro-apoptotic family members, such as Bax, Noxa or PUMA, are transcriptional targets of p53. In addition, transcription-independent, pro-apoptotic activities of p53 have been described. The elucidation of the p53-dependent pathway, resulting in mitochondrial outer membrane permeabilization through the pro-apoptotic Bcl-2 family proteins, is a key to unveiling the mechanism of stress-induced apoptosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0300-5127
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
684-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Mechanisms of p53-dependent apoptosis.
pubmed:affiliation
Department of Medicine III, Johannes Gutenberg University, 55101 Mainz, Germany.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review, Research Support, Non-U.S. Gov't