Recruitment and Activation of RSK2 by HIV-1 Tat

• Published in: PloS one Vol. 2; no. 1; p. e151
• Main Authors: Hetzer, Claudia, Bisgrove, Dwayne, Cohen, Michael S., Pedal, Angelika, Kaehlcke, Katrin, Speyerer, Anja, Bartscherer, Kerstin, Taunton, Jack, Ott, Melanie
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17.01.2007; Public Library of Science (PLoS)
• Subjects: Activation; Amino acids; Animals; Apoptosis; Biochemistry/Transcription and Translation; Cell Line; Chromatin; Coffin-Lowry syndrome; Coffin-Lowry Syndrome - enzymology; Coffin-Lowry Syndrome - genetics; Enzyme inhibitors; Event-related potentials; Gene Products, tat - genetics; Gene Products, tat - metabolism; Genes; Histones - metabolism; HIV; HIV Infections - genetics; HIV-1 - genetics; HIV-1 - metabolism; Human immunodeficiency virus; Humans; Immunology; Infectious Diseases/HIV Infection and AIDS; Kinases; Molecular Biology/Histone Modification; Mutation; Phosphorylation; Phosphotransferases; Proteins; Ribosomal protein S6 kinase; Ribosomal Protein S6 Kinases, 90-kDa - genetics; Ribosomal Protein S6 Kinases, 90-kDa - metabolism; RNA polymerase; Signal transduction; Tat protein; Terminal Repeat Sequences - genetics; Transcription; Transcription factors; Transcriptional Activation; Virology; Virology/Immunodeficiency Viruses; Virology/Viral and Gene Regulation; Virus Replication - genetics; United States > US; San Francisco California; California
• DOI: 10.1371/journal.pone.0000151
• ISSN: 1932-6203

The transcriptional activity of the integrated HIV provirus is dependent on the chromatin organization of the viral promoter and the transactivator Tat. Tat recruits the cellular pTEFb complex and interacts with several chromatin-modifying enzymes, including the histone acetyltransferases p300 and PCAF. Here, we examined the interaction of Tat with activation-dependent histone kinases, including the p90 ribosomal S6 kinase 2 (RSK2). Dominant-negative RSK2 and treatment with a small-molecule inhibitor of RSK2 kinase activity inhibited the transcriptional activity of Tat, indicating that RSK2 is important for Tat function. Reconstitution of RSK2 in cells from subjects with a genetic defect in RSK2 expression (Coffin-Lowry syndrome) enhanced Tat transactivation. Tat interacted with RSK2 and activated RSK2 kinase activity in cells. Both properties were lost in a mutant Tat protein (F38A) that is deficient in HIV transactivation. Our data identify a novel reciprocal regulation of Tat and RSK2 function, which might serve to induce early changes in the chromatin organization of the HIV LTR.