Regulation of HIV-1 Transcription by Protein Phosphatase 1

Authors: Nekhai, Sergei; Jerebtsova, Marina; Jackson, Angela; Southerland, William

Source: Current HIV Research, Volume 5, Number 1, January 2007 , pp. 3-9(7)

Publisher: Bentham Science Publishers

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Abstract:

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 Cterminal 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.

Keywords: HIV-1; Tat; protein phosphatase-1; protein phosphatase 2A; CDK9 phosphorylation

Document Type: Research article

DOI: http://dx.doi.org/10.2174/157016207779316279

Affiliations: 1: Center for Sickle Cell Disease,Howard University, 2121 Georgia Ave., N. W. Washington DC 20059,USA.

Publication date: 2007-01-01

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Current HIV Research aims to cover all the latest and outstanding developments of HIV research. We invite comprehensive review articles and novel, pioneering work in the basic and clinical fields on all areas of HIV research, including virus replication and gene expression, HIV assembly, virus-cell interaction, viral pathogenesis, epidemiology and transmission, anti-retroviral therapy and adherence, drug discovery, the latest developments in HIV/AIDS vaccines and animal models, mechanisms and interactions with AIDS related diseases, social and public health issues related to HIV disease, and prevention of viral infection. Each issue of the journal contains a series of timely in-depth reviews and original research written by leaders in the field covering a range of current topics on HIV research. Periodically, the journal will invite guest editors to devote an issue on a particular area of HIV research of great interest that increases our understanding of the virus and its complex interaction with the host.

Regulation of HIV-1 Transcription by Protein Phosphatase 1

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