Regulation of HIV-1 transcription by protein phosphatase 1.
The emergence of drug-resistant HIV-1 strains presents a challenge for the design of new drugs. Targeting host cell factors involved in the regulation of HIV-1 replication might be one way to overcome the resistance of HIV-1 to anti-viral agents. Our recent studies identified protein phosphatase-1 (PP1) as an important regulator of HIV-1 transcription. Transcription of HIV-1 genes is activated by HIV-1 Tat protein that induces phosphorylation of the C-terminal domain of RNA polymerase-II by CDK9/cyclin T1. We have shown that HIV-1 Tat binds PP1 in vitro; targets PP1 to the nucleus; and that Tat interaction with PP1 is important for HIV-1 transcription. In this review, we discuss two potential targets of PP1 in Tat-induced HIV-1 transcription: the C-terminal domain of RNA polymerase-II and CDK9. We also present a computer model of Tat-PP1 complex that might be useful for future drug design in anti-HIV-1 therapeutics.
Nekhai
Sergei
S
Center for Sickle Cell Disease, Howard University, Washington, DC 20059, USA. snekhai@howard.edu
Jerebtsova
Marina
M
Jackson
Angela
A
Southerland
William
W
D019380:Anti-HIV Agents / Q000494:pharmacology; D003198:Computer Simulation; D042863:Cyclin-Dependent Kinase 9 / Q000378:metabolism; D015696:Gene Products, tat / Q000502:physiology; D015497:HIV-1 / Q000235:genetics*; D008958:Models, Molecular; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000502:physiology*; D010766:Phosphorylation; D054645:Protein Phosphatase 1; D012319:RNA Polymerase II / Q000737:chemistry / Q000378:metabolism; D014158:Transcription, Genetic; D054322:tat Gene Products, Human Immunodeficiency Virus
D019380:Anti-HIV Agents; D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus; D042863:Cyclin-Dependent Kinase 9; D012319:RNA Polymerase II; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1