Regulatory functions of Cdk9 and of cyclin T1 in HIV Tat transactivation pathway gene expression

HIV-1 gene expression relies upon a complex machinery that is primarily con trolled by two viral regulatory proteins, Tat and Rev. Rev is involved in r egulating post-transcriptional events of HIV-1 gene expression. The Tat pro tein transactivates transcription from the HIV-1 S' long terminal repeat (L TR) and acts in synergy with specific cellular factors. Recently, it has be en shown that one set of these cellular factors is a protein kinase activit y termed TAK (Tat-associated kinase), which activates transcription by hype rphosphorylation of the carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase II. TAK also enhances transcription of HIV-2, together w ith the retroviral transactivator, Tat-2. The TAK activity appears to be re lated to the CTD kinase P-TEFb, which stabilizes transcription elongation o f many genes and was originally isolated from Drosophila extracts. Both TAK and P-TEFb contain at least two subunits: the cyclin-dependent kinase, CDK 9 (PITALRE), the catalytic subunit, and the regulatory subunit, cyclin T1. CDK9 and cyclin T1 are ubiquitous factors that affects many cellular proces ses, including cell differentiation and apoptosis. The involvement of TAK i n HIV-1 and HIV-2 gene expression is an important aspect in the biology of these two retroviruses, and may lead to the development of novel antiretrov iral drugs and/or gene therapy approaches for the treatment of patients wit h AIDS. J. Cell. Biochem. 75:357-368, 1999. (C) 1999 Wiley-Liss, Inc.