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  • HMBA releases P-TEFb from HEXIM1 and 7SK snRNA via PI3K/Akt and activities HIV transcription
    Contreras, Xavier ...
    Hexamethylene bisacetamide (HMBA) is a potent inducer of cell differentiation and HIV production in chronically infected cells. However, its mechanism of action remains poorly defined. In this study, ... we demonstrate that HMBA activates transiently the PI3K/Act pathway, which leads to the phosphorylation of HEXIM1 and the subsequent release of active positive transcription elongation factor b (P-TEFb) from its transcriptionally inactivecomplex with HEXIM1 and 7SK small nuclear RNA (snRNA). As a result, P-TEFb is recruited tothe HIV promotoer to stimulate transcription elongation and viral production. Despite the continuous presence of HMBA, the released P-TEFb reassembles rapidly with 7SK sn RNA and HEXIM1. In contrast, a mutant HEXIM1 protein that cannot be phosphorrylated and released from P-TEFb and 7SK snRNA via the PI3K/Act pathway antagonizes this HMBA-mediated induction of viral production. Thus, our studies reveal how transcription is induced by HMBA and suggest how modifications in the equilibrium between active and inactive P-TEFb could contribute to cell differentiation.
    Vir: PLOS pathogens. - ISSN 1553-7366 (Letn. 3, št. 10, 2007, str. 1459-1469)
    Vrsta gradiva - članek, sestavni del
    Leto - 2007
    Jezik - angleški
    COBISS.SI-ID - 2204808

    Povezava(-e):

    http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.0030146
    Repozitorij Univerze v Ljubljani – RUL
    DOI

vir: PLOS pathogens. - ISSN 1553-7366 (Letn. 3, št. 10, 2007, str. 1459-1469)
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