Control of the histone-acetyltransferase activity of Tip60 by the HIV-1 transactivator protein, Tat.
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.
Equipe de Chromatine et Expression des Génes, Equipe d'Assemblage et Régulation de l'Appareil Génétique, Laboratoire de Biologie Moléculaire et Cellulaire de la Différenciation, INSERM U309, France.
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Creaven
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Hans
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Mutskov
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Col
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Caron
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Dimitrov
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Khochbin
D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000595:Amino Acid Sequence; D004789:Enzyme Activation / Q000235:genetics; D015696:Gene Products, tat / Q000378:metabolism / Q000502:physiology*; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D008345:Manganese / Q000737:chemistry; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D008345:Manganese; D013482:Superoxide Dismutase; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5