Bieniasz P D, Grdina T A, Bogerd H P, Cullen B R
Howard Hughes Medical Institute and Department of Genetics, Box 3025, Room 426, CARL Building, Duke University Medical Center, Research Drive, Durham, NC 27710, USA.
EMBO J. 1998 Dec 1;17(23):7056-65. doi: 10.1093/emboj/17.23.7056.
Human cyclin T1 (hCycT1), a major subunit of the essential elongation factor P-TEFb, has been proposed to act as a cofactor for human immunodeficiency virus type 1 (HIV-1) Tat. Here, we show that murine cyclin T1 (mCycT1) binds the activation domain of HIV-1 Tat but, unlike hCycT1, cannot mediate Tat function because it cannot be recruited efficiently to TAR. In fact, overexpression of mCycT1, but not hCycT1, specifically inhibits Tat-TAR function in human cells. This discordant phenotype results from a single amino acid difference between hCycT1 and mCycT1, a tyrosine in place of a cysteine at residue 261. These data indicate that the ability of Tat to recruit CycT1/P-TEFb to TAR determines the species restriction of HIV-1 Tat function in murine cells and therefore demonstrate that this recruitment is a critical function of the Tat protein.
人细胞周期蛋白T1（hCycT1）是必需延伸因子P-TEFb的主要亚基，被认为可作为1型人类免疫缺陷病毒（HIV-1）反式激活因子（Tat）的辅助因子。在此，我们发现小鼠细胞周期蛋白T1（mCycT1）能结合HIV-1 Tat的激活结构域，但与hCycT1不同，它不能介导Tat功能，因为它不能有效地被募集到TAR。事实上，mCycT1（而非hCycT1）的过表达会特异性抑制人类细胞中的Tat-TAR功能。这种不一致的表型源于hCycT1和mCycT1之间的单个氨基酸差异，即第261位残基处的酪氨酸取代了半胱氨酸。这些数据表明，Tat将CycT1/P-TEFb募集到TAR的能力决定了HIV-1 Tat功能在小鼠细胞中的物种限制，因此证明这种募集是Tat蛋白的关键功能。
