Weissman J D, Brown J A, Howcroft T K, Hwang J, Chawla A, Roche P A, Schiltz L, Nakatani Y, Singer D S
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11601-6. doi: 10.1073/pnas.95.20.11601.
HIV Tat, a transactivator of viral transcription, represses transcription of major histocompatibility (MHC) class I genes. Repression depends exclusively on the C-terminal domain of Tat, although the mechanism of this repression has not been known. We now show that repression results from the interaction of Tat with the TAFII250 component of the general transcription factor, TFIID. The C-terminal domain of Tat binds to a site on TAFII250 that overlaps the histone acetyl transferase domain, inhibiting TAFII250 histone acetyl transferase activity. Furthermore, promoters repressed by Tat, including the MHC class I promoter, are dependent on TAFII250 whereas those that are not repressed by Tat, such as SV40 and MuLV promoters, are independent of functional TAFII250. Thus, Tat repression of MHC class I transcription would be one mechanism by which HIV avoids immune surveillance.
HIV反式激活蛋白Tat是病毒转录的反式激活因子，可抑制主要组织相容性复合体（MHC）I类基因的转录。这种抑制作用完全取决于Tat的C末端结构域，尽管这种抑制机制尚不清楚。我们现在发现，这种抑制是由于Tat与通用转录因子TFIID的TAFII250组分相互作用所致。Tat的C末端结构域与TAFII250上一个与组蛋白乙酰转移酶结构域重叠的位点结合，从而抑制TAFII250的组蛋白乙酰转移酶活性。此外，受Tat抑制的启动子，包括MHC I类启动子，依赖于TAFII250，而那些不受Tat抑制的启动子，如SV40和MuLV启动子，则不依赖于功能性TAFII250。因此，Tat对MHC I类转录的抑制可能是HIV逃避免疫监视的一种机制。
