| pubmed-article:16533807 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:16533807 | lifeskim:mentions | umls-concept:C1326205 | lld:lifeskim |
| pubmed-article:16533807 | lifeskim:mentions | umls-concept:C0033684 | lld:lifeskim |
| pubmed-article:16533807 | lifeskim:mentions | umls-concept:C0376515 | lld:lifeskim |
| pubmed-article:16533807 | lifeskim:mentions | umls-concept:C0920533 | lld:lifeskim |
| pubmed-article:16533807 | lifeskim:mentions | umls-concept:C1314939 | lld:lifeskim |
| pubmed-article:16533807 | pubmed:issue | 24 | lld:pubmed |
| pubmed-article:16533807 | pubmed:dateCreated | 2006-6-12 | lld:pubmed |
| pubmed-article:16533807 | pubmed:abstractText | Activator protein 2alpha (AP-2alpha) induces cytotoxicity by inducing cell cycle arrest and apoptosis. In this study we investigated the mechanism of apoptosis induction by AP-2alpha. We found that AP-2alpha induced apoptosis efficiently in cells treated with benzyloxycar-bonyl-IETD-fluoromethyl ketone or FADD-silenced cells but failed to do so in benzyloxycarbonyl-LEHD-fluoromethyl ketone-treated or apoptosis protease activation factor-1 (Apaf1)-silenced cells, suggesting the central role of mitochondria in AP-2alpha-induced apoptosis. In good correlation, cells overexpressing AP-2alpha showed a reduction in mitochondrial membrane potential (Deltapsi(m)), cytochrome c and Smac/DIABLO release into cytosol, and Bax translocation into mitochondria. We found that the pro-apoptotic protein Bax is important for AP-2alpha-induced apoptosis as adenovirus AP2 failed to induce apoptosis in HCT116 Bax(-/-) cells. However, we found the IAP (inhibitor of apoptosis) inhibitor Smac/DIABLO may have a limited role in AP-2alpha-induced apoptosis as we found the IAP member Survivin down-regulated by AP-2alpha. Although the total Bax level remains unaltered, we found a time-dependent increase in the activated form of Bax in adenovirus AP2-infected cells. In addition, we show that AP-2alpha transcriptionally represses Bcl-2 by binding to its promoter both in vitro and in vivo and that this is essential for AP-2alpha-induced apoptosis as ectopic expression of Bcl-2 efficiently inhibited apoptosis induced by AP-2alpha. Furthermore, we show that chemotherapy-induced endogenous AP-2alpha down-regulates Bcl-2 and induces apoptosis in an AP-2alpha-dependent manner. Moreover, we demonstrate that inhibition of okadaic acid or staurosporine-sensitive pathways in AP-2alpha overexpressing breast cancer cells resulted in AP-2alpha-dependent apoptosis induction. These results suggest that AP-2alpha induces apoptosis by down-regulating Bcl-2 and utilizing a bax/cytochrome c/Apaf1/caspase 9-dependent mitochondrial pathway. | lld:pubmed |
| pubmed-article:16533807 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16533807 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16533807 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:16533807 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16533807 | pubmed:month | Jun | lld:pubmed |
| pubmed-article:16533807 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:16533807 | pubmed:author | pubmed-author:SomasundaramK... | lld:pubmed |
| pubmed-article:16533807 | pubmed:author | pubmed-author:WajapeyeeNare... | lld:pubmed |
| pubmed-article:16533807 | pubmed:author | pubmed-author:BrittoRamonaR | lld:pubmed |
| pubmed-article:16533807 | pubmed:author | pubmed-author:RavishankarHa... | lld:pubmed |
| pubmed-article:16533807 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:16533807 | pubmed:day | 16 | lld:pubmed |
| pubmed-article:16533807 | pubmed:volume | 281 | lld:pubmed |
| pubmed-article:16533807 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:16533807 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:16533807 | pubmed:pagination | 16207-19 | lld:pubmed |
| pubmed-article:16533807 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
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| pubmed-article:16533807 | pubmed:meshHeading | pubmed-meshheading:16533807... | lld:pubmed |
| pubmed-article:16533807 | pubmed:year | 2006 | lld:pubmed |
| pubmed-article:16533807 | pubmed:articleTitle | Apoptosis induction by activator protein 2alpha involves transcriptional repression of Bcl-2. | lld:pubmed |
| pubmed-article:16533807 | pubmed:affiliation | Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012, India. | lld:pubmed |
| pubmed-article:16533807 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:16533807 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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