Control of the histone-acetyltransferase activity of Tip60 by the HIV-1 transactivator protein, Tat. NLM AIDSLINE Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

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Control of the histone-acetyltransferase activity of Tip60 by the HIV-1 transactivator protein, Tat.

Biochemistry. 1999 Jul 6;38(27):8826-30. Unique Identifier : AIDSLINE MED/99321520
Creaven M; Hans F; Mutskov V; Col E; Caron C; Dimitrov S; Khochbin S; Equipe de Chromatine et Expression des Genes, Equipe; d'Assemblage et Regulation de l'Appareil Genetique,; Laboratoire de Biologie Moleculaire et Cellulaire de la; Differenciation, INSERM U309, France.

Abstract: Tip60, a cellular histone-acetyltransferase, is known to interact with the HIV-1-encoded transactivator protein, Tat. In this work, we show that the interaction of Tat with Tip60 efficiently inhibits the Tip60 histone-acetyltransferase activity. Besides its histone-acetyltransferase activity, Tip60 can undergo an autoacetylation which is not affected by Tat interaction. Our data show that Tip60 does not significantly influence Tat-dependent transcriptional activation of the 5'-LTR of HIV, suggesting that its interaction with Tat affects some intrinsic cellular process. We were then able to identify a cellular gene, Mn-dependent superoxide dismutase (Mn-SOD), that has a Tip60-dependent transcriptional activity. Interestingly, the simultaneous expression of Tat and Tip60 abolishes the effect of Tip60 on the activity of the Mn-SOD promoter. We postulate that the HIV-1 transactivator, Tat, in targeting Tip60 hinders the expression of cellular genes (such as Mn-SOD) which normally interfere with the efficient replication and propagation of the virus.
Keywords: JOURNAL ARTICLE Acetyltransferases/ANTAGONISTS & INHIB/*METABOLISM Amino Acid Sequence Enzyme Activation/GENETICS Gene Products, tat/METABOLISM/*PHYSIOLOGY Hela Cells Human HIV Long Terminal Repeat/GENETICS HIV-1/*PHYSIOLOGY Manganese/CHEMISTRY Molecular Sequence Data Promoter Regions (Genetics) Proteins/ANTAGONISTS & INHIB/*METABOLISM/PHYSIOLOGY Superoxide Dismutase/GENETICS/METABOLISM Support, Non-U.S. Gov't Transcription, GeneticKWDjournalarticleacetyltransferases/antagonists&inhib/KWDmetabolismaminoacidsequenceenzymeactivation/geneticsgeneproducts,tat/metabolism/KWDphysiologyhelacellshumanhivlongterminalrepeat/geneticshiv-1/KWDphysiologymanganese/chemistrymolecularsequencedatapromoterregions(genetics)proteins/antagonists&inhib/KWDmetabolism/physiologysuperoxidedismutase/genetics/metabolismsupport,non-uKWDsKWDgov'ttranscription,genetic
991030
A99A0970

Copyright © 1999 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

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