| pubmed-article:11602639 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:11602639 | lifeskim:mentions | umls-concept:C0019704 | lld:lifeskim |
| pubmed-article:11602639 | lifeskim:mentions | umls-concept:C0162638 | lld:lifeskim |
| pubmed-article:11602639 | lifeskim:mentions | umls-concept:C0031715 | lld:lifeskim |
| pubmed-article:11602639 | lifeskim:mentions | umls-concept:C0079419 | lld:lifeskim |
| pubmed-article:11602639 | lifeskim:mentions | umls-concept:C1422036 | lld:lifeskim |
| pubmed-article:11602639 | lifeskim:mentions | umls-concept:C1414805 | lld:lifeskim |
| pubmed-article:11602639 | lifeskim:mentions | umls-concept:C1314939 | lld:lifeskim |
| pubmed-article:11602639 | pubmed:issue | 8 | lld:pubmed |
| pubmed-article:11602639 | pubmed:dateCreated | 2001-10-16 | lld:pubmed |
| pubmed-article:11602639 | pubmed:abstractText | Syncytia arising from the fusion of cells expressing a lymphotropic human immunodeficiency virus (HIV)-1-encoded envelope glycoprotein complex (Env) gene with cells expressing the CD4/CXCR4 complex undergo apoptosis through a mitochondrion-controlled pathway initiated by the upregulation of Bax. In syncytial apoptosis, phosphorylation of p53 on serine 15 (p53S15) precedes Bax upregulation, the apoptosis-linked conformational change of Bax, the insertion of Bax in mitochondrial membranes, subsequent release of cytochrome c, caspase activation, and apoptosis. p53S15 phosphorylation also occurs in vivo, in HIV-1(+) donors, where it can be detected in preapoptotic and apoptotic syncytia in lymph nodes, as well as in peripheral blood mononuclear cells, correlating with viral load. Syncytium-induced p53S15 phosphorylation is mediated by the upregulation/activation of mammalian target of rapamycin (mTOR), also called FKBP12-rapamycin-associated protein (FRAP), which coimmunoprecipitates with p53. Inhibition of mTOR/FRAP by rapamycin reduces apoptosis in several paradigms of syncytium-dependent death, including in primary CD4(+) lymphoblasts infected by HIV-1. Concomitantly, rapamycin inhibits p53S15 phosphorylation, mitochondrial translocation of Bax, loss of the mitochondrial transmembrane potential, mitochondrial release of cytochrome c, and nuclear chromatin condensation. Transfection with dominant negative p53 has a similar antiapoptotic action as rapamycin, upstream of the Bax upregulation/translocation. In summary, we demonstrate that phosphorylation of p53S15 by mTOR/FRAP plays a critical role in syncytial apoptosis driven by HIV-1 Env. | lld:pubmed |
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| pubmed-article:11602639 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:11602639 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:11602639 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:11602639 | pubmed:month | Oct | lld:pubmed |
| pubmed-article:11602639 | pubmed:issn | 0022-1007 | lld:pubmed |
| pubmed-article:11602639 | pubmed:author | pubmed-author:MétivierDD | lld:pubmed |
| pubmed-article:11602639 | pubmed:author | pubmed-author:BlancoJJ | lld:pubmed |
| pubmed-article:11602639 | pubmed:author | pubmed-author:KroemerGG | lld:pubmed |
| pubmed-article:11602639 | pubmed:author | pubmed-author:PiacentiniMM | lld:pubmed |
| pubmed-article:11602639 | pubmed:author | pubmed-author:AmendolaAA | lld:pubmed |
| pubmed-article:11602639 | pubmed:author | pubmed-author:CastedoMM | lld:pubmed |
| pubmed-article:11602639 | pubmed:author | pubmed-author:NardacciRR | lld:pubmed |
| pubmed-article:11602639 | pubmed:author | pubmed-author:EsteJ AJA | lld:pubmed |
| pubmed-article:11602639 | pubmed:author | pubmed-author:LarochetteNN | lld:pubmed |
| pubmed-article:11602639 | pubmed:author | pubmed-author:BarretinaJJ | lld:pubmed |
| pubmed-article:11602639 | pubmed:author | pubmed-author:FerriK FKF | lld:pubmed |
| pubmed-article:11602639 | pubmed:author | pubmed-author:RoumierTT | lld:pubmed |
| pubmed-article:11602639 | pubmed:issnType | Print | lld:pubmed |
