PCAF interacts with tax and stimulates tax transactivation in a histone acetyltransferase-independent manner

Recent studies have shown that the p300/CREB binding protein (CBP)-associat ed factor (PCAF) is involved in transcriptional activation. PCAF activity h as been shown strongly associated with histone acetyltransferase (HAT) acti vity. In this report, we present evidence for a HAT-independent transcripti on function that is activated in the presence of the human T-cell leukemia virus type (HTLV-1) Tax protein. In vitro and in vivo GST-Tax pull-down and coimmunoprecipitation experiments demonstrate that there is a direct inter action between Tax and PCAF, independent of p300/CBP. PCAF can be recruited to the HTLV-1 Tax responsive element in the presence of Tax, and PCAF coop erates with Tax in vivo to activate transcription from the HTLV-I LTR over 10-fold. Point mutations at Tax amino acid 318 (TaxS318A) or 319 to 320 (Ta x M47), which have decreased or no activity on the HTLV-1 promoter, are def ective for PCAF binding. Strikingly, the ability of PCAF to stimulate Tax t ransactivation is not solely dependent on the PCAF HAT domain. Tao independ ent PCAF RAT mutants, which knock out acetyltransferase enzyme activity, ac tivate Tax transactivation to approximately the same level as wild-type PCA F. In contrast, p300 stimulation of Tax transactivation is HAT dependent. T hese studies provide experimental evidence that PCAF contains a coactivator transcription function independent of the RAT activity on the viral long t erminal repeat.