Linked Life Data

21423217

Source:http://linkedlifedata.com/resource/pubmed/id/21423217

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
33
pubmed:dateCreated
2011-8-18
pubmed:abstractText
BH3-only protein Bid is a key player in death receptor-induced apoptosis, because it provides the link with the mitochondrial route for caspase activation. In this pathway, Bid is activated upon cleavage by caspase-8. Its BH3 domain-containing carboxy-terminal fragment subsequently provokes mitochondrial outer membrane permeabilization by Bak/Bax activation. Bid has also been implicated in the apoptotic response to ionizing radiation (IR) and the topoisomerase inhibitor etoposide, anti-cancer regimens that cause double-strand (ds)DNA breaks. We confirm the existence of this pathway and show that it is p53-independent. However, the degree of Bid participation in the apoptotic response to dsDNA breaks depends on the nature of cell transformation. We used Bid-deficient mouse embryonic fibroblast (MEF) lines that were reconstituted with Bid to control the cellular background and demonstrated that the Bid-dependent apoptotic pathway induced by IR and etoposide operates in MEFs that are transformed by SV40, but is not evident in E1A/Ras-transformed MEFs. The Bid-dependent apoptotic response in p53-deficient SV40-transformed MEFs contributed to clonogenic execution of the cells, implying relevance for treatment outcome. In these cells, Bid acted in a conventional manner in that it required its BH3 domain to mediate apoptosis in response to IR and etoposide, and triggered apoptotic execution by indirect activation of Bak/Bax, mitochondrial permeabilization and caspase-9 activation. However, the mechanism of Bid activation was unconventional, because elimination of all known or suspected cleavage sites for caspases or other proteolytic enzymes and even complete elimination of its unstructured cleavage loop left Bid's pro-apoptotic role in the response to IR and etoposide unaffected.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
18
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3636-47
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Bid can mediate a pro-apoptotic response to etoposide and ionizing radiation without cleavage in its unstructured loop and in the absence of p53.
pubmed:affiliation
Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't