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  • Tat competes with HEXIM1 to increase the active pool of P-TEFb for HIV-1 transcription
    Barborič, Matjaž, 1975- ...
    Human immunodeficiency virus type 1 (HIV-1) transcriptional transactivator (Tat) recruits the positive transcription elongation factor b (P-TEFb) to the viral promoter. Consisting of cyclin dependent ... kinase 9 (Cdk9) and cyclin T1, P-TEFb phosphorylates RNA polymerase II and the negative transcription elongation factor to stimulate the elongation of HIV-1 genes. A major fractionof nuclear P-TEFb is sequestered into a transcriptionally inactive 7SKsmall nuclear ribonucleoprotein (snRNP) by the coordinated actions of the 7SK small nuclear RNA (snRNA) and hexamethylene bisacetamide (HMBA) induced protein 1 (HEXIM1). In this study, we demonstrate that Tat prevents the formation of and also releases P-TEFb from the 7SK snRNP in vitro and in vivo. This ability of Tat depends on the integrity of its N-terminal activation domain and stems from the high affinity interaction between Tat andcyclin T1, which allows Tat to directly displace HEXIM1 from cyclin T1. Furthermore, we find that in contrast to the Tat-independent activation of theHIV-1 promoter, Tat-dependent HIV-1 transcription is largely insensitive tothe inhibition by HEXIM1. Finally, primary blood lymphocytes display a reduced amount of the endogenous 7SK snRNP upon HIV-1 infection. All these data are consistent with the model that Tat not only recruits but also increases the active pool of P-TEFb for efficient HIV-1 transcription.
    Vir: Nucleic acids research. - ISSN 0305-1048 (Vol. 35, issue 6, 2007, str. 2003-2012)
    Vrsta gradiva - članek, sestavni del
    Leto - 2007
    Jezik - angleški
    COBISS.SI-ID - 29182681
    DOI

vir: Nucleic acids research. - ISSN 0305-1048 (Vol. 35, issue 6, 2007, str. 2003-2012)
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