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 i nteraction of Tar with Tip60 efficiently inhibits the Tip60 histone-acetylt ransferase activity. Besides its histone-acetyltransferase activity, Tip60 can undergo an autoacetylation which is not affected by Tat interaction. Ou r data show that Tip60 does not significantly influence Tat-dependent trans criptional activation of the S-LTR of HIV, suggesting that its interaction with Tat affects same intrinsic cellular process. We were then able to iden tify 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 o f 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) w hich normally interfere with the efficient replication and propagation of t he virus.