Tat介导的HIV-1转录延伸
中文名称
通路描述
Tat蛋白是一种病毒转激活蛋白，通过控制RNA Pol II介导的延伸来调节HIV-1基因表达（综述见Karn 1999; Taube et al. 1999; Liou et al. 2004; Barboric and Peterlin 2005）。Tat似乎对于克服RNA Pol II因DSIF和NELF负转录延伸因子而停滞至关重要（Wada et al. 1998; Yamaguchi et al. 1999; Yamaguchi et al 2002; Fujinaga et al. 2004）。虽然Pol II可以在没有Tat的情况下与 proviral LTR结合并启动转录，但这些聚合酶复合物是非进程性的，会过早从模板上解离，产生非常短的转录本（Kao et al. 1987）。Tat与TAR结合，该序列在领头RNA中形成茎环结构（Dingwall et al. 1989）。Tat还与细胞质激酶复合物P-TEFb(Cyclin T1:Cdk9)结合，并将其招募到TAR茎环结构上（Herrmann, 1995）（Wei et al. 1998）。Tat、TAR和P-TEFb(Cyclin T1:Cdk9)之间的这种关联被认为将这种激酶催化亚基（Cdk9）的催化亚基与Pol II的CTD置于近距离，使其超磷酸化（Zhou et al. 2000）。NELF的RD亚基和DSIF的SPT5亚基，通过RD与TAR的底部茎环结合，也被P-TEFb(Cyclin T1:Cdk9)磷酸化（Yamaguchi et al. 2002; Fujinaga et al. 2004; Ivanov et al. 2000）。磷酸化RD导致其从TAR上解离。因此，Tat似乎通过超磷酸化RNA Pol II的CTD并移除TAR上的负转录延伸因子来促进HIV-1转录本的延伸。此外，有证据表明Tat与P-TEFb(Cyclin T1:Cdk9)的结合改变了P-TEFb的底物特异性，增强了CTD上Ser5残基的磷酸化（Zhou et al. 2000）。
英文描述
Tat-mediated elongation of the HIV-1 transcript The Tat protein is a viral transactivator protein that regulates HIV-1 gene expression by controlling RNA Pol II-mediated elongation (reviewed in Karn 1999; Taube et al. 1999; Liou et al. 2004; Barboric and Peterlin 2005). Tat appears to be required in order to overcome the arrest of RNA Pol II by the negative transcriptional elongation factors DSIF and NELF (Wada et al. 1998; Yamaguchi et al. 1999; Yamaguchi et al 2002; Fujinaga et al. 2004). While Pol II can associate with the proviral LTR and initiate transcription in the absence of Tat, these polymerase complexes are non-processive and dissociate from the template prematurely producing very short transcripts (Kao et al. 1987). Tat associates with the RNA element, TAR, which forms a stem loop structure in the leader RNA sequence (Dingwall et al. 1989). Tat also associates with the cellular kinase complex P-TEFb(Cyclin T1:Cdk9) and recruits it to the TAR stem loop structure (Herrmann, 1995) (Wei et al. 1998). This association between Tat, TAR and P-TEFb(Cyclin T1:Cdk9) is believed to bring the catalytic subunit of this kinase complex (Cdk9) in close proximity to Pol II where it hyperphosphorylates the CTD of RNA Pol II (Zhou et al. 2000). The RD subunits of NELF and the SPT5 subunit of DSIF, which associate through RD with the bottom stem of TAR, are also phosphorylated by P-TEFb(Cyclin T1:Cdk9) (Yamaguchi et al. 2002; Fujinaga et al. 2004; Ivanov et al. 2000). Phosphorylation of RD results in its dissociation from TAR. Thus, Tat appears to facilitate transcriptional elongation of the HIV-1 transcript by hyperphosphorylating the RNA Poll II CTD and by removing the negative transcription elongation factors from TAR. In addition, there is evidence that the association of Tat with P-TEFb(Cyclin T1:Cdk9) alters the substrate specificity of P-TEFb enhancing phosphorylation of ser5 residues in the CTD of RNA Pol II (Zhou et al. 2000).
所含基因
39 个基因