Recruitment and activation of RSK2 by HIV-1 Tat

Claudia Hetzer, Dwayne Bisgrove, Michael Cohen, Angelika Pedal, Katrin Kaehlcke, Anja Speyerer, Kerstin Bartscherer, Jack Taunton, Melanie Ott

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere151
JournalPLoS One
Volume2
Issue number1
DOIs
StatePublished - Jan 17 2007
Externally publishedYes

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Human immunodeficiency virus 1
HIV-1
phosphotransferases (kinases)
Chemical activation
Chromatin
HIV
chromatin
Transcriptional Activation
Coffin-Lowry Syndrome
90-kDa Ribosomal Protein S6 Kinases
transcriptional activation
Phosphotransferases
Protamine Kinase
tat Gene Products
Histone Acetyltransferases
ribosomal protein S6 kinase, 90kDa, polypeptide 3
Proviruses
Trans-Activators
Mutant Proteins
proviruses

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Hetzer, C., Bisgrove, D., Cohen, M., Pedal, A., Kaehlcke, K., Speyerer, A., ... Ott, M. (2007). Recruitment and activation of RSK2 by HIV-1 Tat. PLoS One, 2(1), [e151]. https://doi.org/10.1371/journal.pone.0000151

Recruitment and activation of RSK2 by HIV-1 Tat. / Hetzer, Claudia; Bisgrove, Dwayne; Cohen, Michael; Pedal, Angelika; Kaehlcke, Katrin; Speyerer, Anja; Bartscherer, Kerstin; Taunton, Jack; Ott, Melanie.

In: PLoS One, Vol. 2, No. 1, e151, 17.01.2007.

Research output: Contribution to journalArticle

Hetzer, C, Bisgrove, D, Cohen, M, Pedal, A, Kaehlcke, K, Speyerer, A, Bartscherer, K, Taunton, J & Ott, M 2007, 'Recruitment and activation of RSK2 by HIV-1 Tat', PLoS One, vol. 2, no. 1, e151. https://doi.org/10.1371/journal.pone.0000151
Hetzer C, Bisgrove D, Cohen M, Pedal A, Kaehlcke K, Speyerer A et al. Recruitment and activation of RSK2 by HIV-1 Tat. PLoS One. 2007 Jan 17;2(1). e151. https://doi.org/10.1371/journal.pone.0000151
Hetzer, Claudia ; Bisgrove, Dwayne ; Cohen, Michael ; Pedal, Angelika ; Kaehlcke, Katrin ; Speyerer, Anja ; Bartscherer, Kerstin ; Taunton, Jack ; Ott, Melanie. / Recruitment and activation of RSK2 by HIV-1 Tat. In: PLoS One. 2007 ; Vol. 2, No. 1.
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