| Domaine : |
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Sciences du Vivant/Biochimie, Biologie Moléculaire
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PMID (identifiant de la référence Pubmed) : |
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(17653867) |
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| Titre : |
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The Siva protein is a novel intracellular ligand of the CD4 receptor that promotes HIV-1 envelope-induced apoptosis in T-lymphoid cells. |
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| Auteur(s) : |
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Bénédicte Py1, Jérôme Bouchet1, Guillaume Jacquot1, Nathalie Sol-Foulon2, Stéphane Basmaciogullari1, Olivier Schwartz2, Martine Biard-Piechaczyk3, Serge Benichou1 |
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| Laboratoire : |
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| Résumé : |
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In addition to its positive signaling function in the antigen presentation process, CD4 acts as the primary receptor for HIV-1. Contact between CD4 and the viral envelope leads to virus entry, but can also trigger apoptosis of uninfected CD4+ T-cells through a mechanism that is poorly understood. We show that Siva-1, a death domain-containing proapoptotic protein, associates with the cytoplasmic domain of CD4. This interaction is mediated by the cysteine-rich region found in the C-terminal part of the Siva-1 protein. Expression of Siva-1 specifically increases the susceptibility of both T-cell lines and unstimulated human primary CD4+ T-lymphocytes to CD4-mediated apoptosis triggered by the HIV-1 envelope, and results in activation of a caspase-dependent mitochondrial pathway. The same susceptibility is observed in T-cells expressing a truncated form of CD4 that is able to recruit Siva-1 but fails to associate with p56Lck, indicating that Siva-1 participates in a pathway independent of the p56Lck kinase activity. Altogether, these results suggest that Siva-1 might participate in the CD4-initiated signaling apoptotic pathway induced by the HIV-1 envelope in T-lymphoid cells. |
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Langue du texte intégral : |
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Anglais |
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| Type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1007/s10495-007-0106-4 |
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| Journal : |
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| Apoptosis (Apoptosis) |
| Publisher |
Springer Verlag (Germany) |
| ISSN |
1360-8185 (eISSN : 1573-675X) |
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| Audience : |
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non spécifiée |
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| Date de publication : |
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10/2007 |
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| Volume : |
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12 |
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| Numéro : |
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10 |
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| Page, identifiant, ... : |
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1879-92 |
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