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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2008-1-14
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pubmed:abstractText |
Activated T cells require anti-apoptotic cytokines for their survival. The anti-apoptotic effects of these factors are mediated by their influence on the balance of expression and localisation of pro- and anti-apoptotic members of the Bcl-2 family. Among the anti-apoptotic Bcl-2 family members, the expression level of Bcl-2 itself and its interaction with the pro-apoptotic protein Bim are now regarded as crucial for the regulation of survival in activated T cells. We studied the changes in Bcl-2 levels and its subcellular distribution in relation to mitochondrial depolarisation and caspase activation in survival factor deprived T cells. Intriguingly, the total Bcl-2 level appeared to remain stable, even after caspase 3 activation indicated entry into the execution phase of apoptosis. However, cell fractionation experiments showed that while the dominant nuclear pool of Bcl-2 remained stable during apoptosis, the level of the smaller mitochondrial pool was rapidly downregulated. Signals induced by anti-apoptotic cytokines continuously replenish the mitochondrial pool, but nuclear Bcl-2 is independent of such signals. Mitochondrial Bcl-2 is lost rapidly by a caspase independent mechanism in the absence of survival factors, in contrast only a small proportion of the nuclear pool of Bcl-2 is lost during the execution phase and this loss is a caspase dependent process. We conclude that these two intracellular pools of Bcl-2 are regulated through different mechanisms and only the cytokine-mediated regulation of the mitochondrial pool is relevant to the control of the initiation of apoptosis.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17957472-10092109,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17957472-9731187
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1360-8185
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pubmed:author |
pubmed-author:AkbarArne NAN,
pubmed-author:AssiLakhvirL,
pubmed-author:BuckleyChristopher DCD,
pubmed-author:CurnowS JohnSJ,
pubmed-author:LamWing YeeWY,
pubmed-author:LordJanet MJM,
pubmed-author:PillingDarrellD,
pubmed-author:RazaKarimK,
pubmed-author:RossEmma JEJ,
pubmed-author:SalmonMikeM,
pubmed-author:Scheel-ToellnerDagmarD
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pubmed:issnType |
Print
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
109-17
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pubmed:dateRevised |
2011-8-1
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pubmed:meshHeading |
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pubmed:year |
2008
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pubmed:articleTitle |
Differential regulation of nuclear and mitochondrial Bcl-2 in T cell apoptosis.
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pubmed:affiliation |
MRC Centre of Immune Regulation, Division of Immunity and Infection, Institute of Biomedical Research, University of Birmingham, Birmingham, UK. d.scheel@bham.ac.uk
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