Recruitment of human cyclin T1 to nuclear bodies through direct interaction with the PML protein
Recruitment of human cyclin T1 to nuclear bodies through direct interaction with the PML protein
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DOI：
10.1093/emboj/cdg205
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发表时间：
2003-05-01
期刊：
影响因子：
11.4
通讯作者：
Giacca, M
中科院分区：
文献类型：
--
作者：
Marcello, A;Ferrari, A;Giacca, M
人细胞周期蛋白T1是正转录延伸因子B（P-TEF B）中Cdk 9激酶的细胞周期蛋白伴侣，是一种必需的细胞辅因子，由人免疫缺陷病毒1型（HIV-1）达特反式激活因子募集以促进从HIV-1长末端重复序列（LTR）的转录延伸。在这里，我们利用荧光共振能量转移（FRET），以证明细胞周期蛋白T1物理相互作用，在体内与早幼粒细胞白血病（PML）蛋白在特定的亚核隔室是一致的PML核体。缺失突变体在C-末端区域的细胞周期蛋白T1是阴性的FRET与PML和未能本地化的核体。还发现细胞周期蛋白T1和PML在核体外相关，并且在达特反式激活后，这两种蛋白质都存在于染色质化的HIV-1 LTR启动子处。综上所述，这些结果表明，PML蛋白调节达特介导的转录激活，通过调节细胞周期蛋白T1和其他必要的辅因子的转录机器的可用性。
Human cyclin T1, the cyclin partner of Cdk9 kinase in the positive transcription elongation factor b (P-TEFb), is an essential cellular cofactor that is recruited by the human immunodeficiency virus type 1 (HIV-1) Tat transactivator to promote transcriptional elongation from the HIV-1 long terminal repeat (LTR). Here we exploit fluorescence resonance energy transfer (FRET) to demonstrate that cyclin T1 physically interacts in vivo with the promyelocytic leukaemia (PML) protein within specific subnuclear compartments that are coincident with PML nuclear bodies. Deletion mutants at the C-terminal region of cyclin T1 are negative for FRET with PML and fail to localize to nuclear bodies. Cyclin T1 and PML are also found associated outside of nuclear bodies, and both proteins are present at the chromatinized HIV-1 LTR promoter upon Tat transactivation. Taken together these results suggest that PML proteins regulate Tat- mediated transcriptional activation by modulating the availability of cyclin T1 and other essential cofactors to the transcription machinery.