Linked Life Data

17237824

Source:http://linkedlifedata.com/resource/pubmed/id/17237824

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
29
pubmed:dateCreated
2007-6-21
pubmed:abstractText
p53-upregulated modulator of apoptosis (PUMA) is a BH3-only Bcl-2 family protein and an essential mediator of DNA damage-induced apoptosis. PUMA is localized in the mitochondria and induces apoptosis through the mitochondrial pathway. However, the mechanisms of PUMA-induced apoptosis remain unclear. In this study, we found that second mitochondria-derived activator of caspase (SMAC)/Diablo, a mitochondrial apoptogenic protein, mediates the proapoptotic function of PUMA by regulating PUMA-induced mitochondrial events. SMAC is consistently released into the cytosol in colon cancer cells undergoing PUMA-induced apoptosis. In SMAC-deficient cells, execution of PUMA-induced apoptosis is abrogated, in company with decreases in caspase activation, cytosolic release of cytochrome c and collapse of mitochondrial membrane potential. Reconstituting SMAC expression restored these events in the SMAC-deficient cells. Furthermore, SMAC and agents that mimic the inhibitor of apoptosis proteins (IAPs) inhibition function of SMAC significantly sensitize cells to PUMA-induced apoptosis. These results demonstrate an important role of SMAC in executing DNA damage-induced and PUMA-mediated apoptosis and suggest that SMAC participates in a feedback amplification loop to promote cytochrome c release and other mitochondrial events in apoptosis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4189-98
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
SMAC/Diablo mediates the proapoptotic function of PUMA by regulating PUMA-induced mitochondrial events.
pubmed:affiliation
Department of Pharmacology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural