Xiao H, Tao Y, Greenblatt J, Roeder R G
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10021, USA.
Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2146-51. doi: 10.1073/pnas.95.5.2146.
Replication of HIV-1 requires the viral Tat protein, which increases the extent of transcription elongation by RNA polymerase II after activation at the single viral long terminal repeat (LTR) promoter. This effect of Tat on transcription requires Tat interactions with a 5' region (TAR) in nascent transcripts as well as Tat-specific cofactors. The present study identifies a cellular protein, TIP30, that interacts with Tat and with an SRB-containing RNA polymerase II complex both in vivo and in vitro. Coexpression of TIP30 specifically enhances transactivation by Tat in transfected cells, and immunodepletion of TIP30 from nuclear extracts abolishes Tat-activated transcription without affecting Tat-independent transcription. These results implicate TIP30 as a specific coactivator that may enhance formation of a Tat-RNA polymerase II holoenzyme complex.
HIV-1的复制需要病毒Tat蛋白,该蛋白在单个病毒长末端重复序列(LTR)启动子激活后,可增加RNA聚合酶II的转录延伸程度。Tat对转录的这种作用需要Tat与新生转录本中的5'区域(TAR)以及Tat特异性辅因子相互作用。本研究鉴定出一种细胞蛋白TIP30,它在体内和体外均能与Tat以及含SRB的RNA聚合酶II复合物相互作用。在转染细胞中,TIP30的共表达特异性增强了Tat的反式激活作用,并且从核提取物中免疫去除TIP30会消除Tat激活的转录,而不影响非Tat依赖性转录。这些结果表明TIP30是一种特异性共激活因子,可能会增强Tat-RNA聚合酶II全酶复合物的形成。