Title: Nuclear targeting of protein phosphatase-1 by HIV-1 Tat protein
Authors: Ammosova, Tatyana ×
Jerebtsova, Marina
Beullens, Monique
Lesage, Bart
Jackson, Angela
Kashanchi, Fatah
Southerland, William
Gordeuk, Victor R
Bollen, Mathieu
Nekhai, Sergei #
Issue Date: Oct-2005
Publisher: American Society for Biochemistry and Molecular Biology
Series Title: Journal of Biological Chemistry vol:280 issue:43 pages:36364-71
Abstract: Transcription of human immunodeficiency virus (HIV)-1 genes is activated by HIV-1 Tat protein, which induces phosphorylation of the C-terminal domain of RNA polymerase-II by CDK9/cyclin T1. We previously showed that Tat-induced HIV-1 transcription is regulated by protein phosphatase-1 (PP1). In the present study we demonstrate that Tat interacts with PP1 and that disruption of this interaction prevents induction of HIV-1 transcription. We show that PP1 interacts with Tat in part through the binding of Val36 and Phe38 of Tat to PP1 and that Tat is involved in the nuclear and subnuclear targeting of PP1. The PP1 binding mutant Tat-V36A/F38A displayed a decreased affinity for PP1 and was a poor activator of HIV-1 transcription. Surprisingly, Tat-Q35R mutant that had a higher affinity for PP1 was also a poor activator of HIV-1 transcription, because strong PP1 binding competed out binding of Tat to CDK9/cyclin T1. Our results suggest that Tat might function as a nuclear regulator of PP1 and that interaction of Tat with PP1 is critical for activation of HIV-1 transcription by Tat.
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Biochemistry Section (Medicine) (-)
Laboratory of Biosignaling & Therapeutics
× corresponding author
# (joint) last author

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