Wei P, Garber M E, Fang S M, Fischer W H, Jones K A
Regulatory Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037-1099, USA.
Cell. 1998 Feb 20;92(4):451-62. doi: 10.1016/s0092-8674(00)80939-3.
The HIV-1 Tat protein regulates transcription elongation through binding to the viral TAR RNA stem-loop structure. We have isolated a novel 87 kDa cyclin C-related protein (cyclin T) that interacts specifically with the transactivation domain of Tat. Cyclin T is a partner for CDK9, an RNAPII transcription elongation factor. Remarkably, the interaction of Tat with cyclin T strongly enhances the affinity and specificity of the Tat:TAR RNA interaction, and confers a requirement for sequences in the loop of TAR that are not recognized by Tat alone. Moreover, overexpression of human cyclin T rescues Tat activity in nonpermissive rodent cells. We propose that Tat directs cyclin T-CDK9 to RNAPII through cooperative binding to TAR RNA.
HIV-1反式激活因子（Tat）蛋白通过与病毒TAR RNA茎环结构结合来调节转录延伸。我们分离出了一种新的87 kDa细胞周期蛋白C相关蛋白（细胞周期蛋白T），它能与Tat的反式激活结构域特异性相互作用。细胞周期蛋白T是RNA聚合酶II（RNAPII）转录延伸因子CDK9的搭档。值得注意的是，Tat与细胞周期蛋白T的相互作用强烈增强了Tat与TAR RNA相互作用的亲和力和特异性，并赋予了对TAR环中Tat单独无法识别的序列的需求。此外，人细胞周期蛋白T的过表达可挽救非允许性啮齿动物细胞中的Tat活性。我们提出，Tat通过与TAR RNA协同结合将细胞周期蛋白T-CDK9导向RNAPII。
