| pubmed-article:12145207 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12145207 | lifeskim:mentions | umls-concept:C0019704 | lld:lifeskim |
| pubmed-article:12145207 | lifeskim:mentions | umls-concept:C0162638 | lld:lifeskim |
| pubmed-article:12145207 | lifeskim:mentions | umls-concept:C1622204 | lld:lifeskim |
| pubmed-article:12145207 | lifeskim:mentions | umls-concept:C0079419 | lld:lifeskim |
| pubmed-article:12145207 | lifeskim:mentions | umls-concept:C1332721 | lld:lifeskim |
| pubmed-article:12145207 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
| pubmed-article:12145207 | lifeskim:mentions | umls-concept:C1314939 | lld:lifeskim |
| pubmed-article:12145207 | lifeskim:mentions | umls-concept:C1705294 | lld:lifeskim |
| pubmed-article:12145207 | pubmed:issue | 15 | lld:pubmed |
| pubmed-article:12145207 | pubmed:dateCreated | 2002-7-29 | lld:pubmed |
| pubmed-article:12145207 | pubmed:abstractText | Syncytia arising from the fusion of cells expressing the HIV-1-encoded Env gene with cells expressing the CD4/CXCR4 complex undergo apoptosis following the nuclear translocation of mammalian target of rapamycin (mTOR), mTOR-mediated phosphorylation of p53 on Ser15 (p53(S15)), p53-dependent upregulation of Bax and activation of the mitochondrial death pathway. p53(S15) phosphorylation is only detected in syncytia in which nuclear fusion (karyogamy) has occurred. Karyogamy is secondary to a transient upregulation of cyclin B and a mitotic prophase-like dismantling of the nuclear envelope. Inhibition of cyclin-dependent kinase-1 (Cdk1) prevents karyogamy, mTOR activation, p53(S15) phosphorylation and apoptosis. Neutralization of p53 fails to prevent karyogamy, yet suppresses apoptosis. Peripheral blood mononuclear cells from HIV-1-infected patients exhibit an increase in cyclin B and mTOR expression, correlating with p53(S15) phosphorylation and viral load. Cdk1 inhibition prevents the death of syncytia elicited by HIV-1 infection of primary CD4 lymphoblasts. Thus, HIV-1 elicits a pro-apoptotic signal transduction pathway relying on the sequential action of cyclin B-Cdk1, mTOR and p53. | lld:pubmed |
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| pubmed-article:12145207 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:12145207 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:12145207 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12145207 | pubmed:month | Aug | lld:pubmed |
| pubmed-article:12145207 | pubmed:issn | 0261-4189 | lld:pubmed |
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