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.
Creaven
M
M
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.
Hans
F
F
Mutskov
V
V
Col
E
E
Caron
C
C
Dimitrov
S
S
Khochbin
S
S
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