Résumé
The HIV‐1 transactivator protein, Tat, is an atypical transcriptional activator that functions through binding, not to DNA, but to a short leader RNA, TAR. Although details of its functional mechanism are still unknown, emerging findings suggest that Tat serves primarily to adapt co‐activator complexes such as p300, PCAF and P‐TEFb to the HIV‐1 long terminal repeat. Hence, an understanding of how Tat interacts with these cofactors is crucial. It has recently been shown that acetylation at a single lysine, residue 50, regulated the association of Tat with PCAF. Here, we report that in the absence of Tat acetylation, PCAF binds to amino acids 20–40 within Tat. Interestingly, acetylation of Tat at Lys28 abrogates Tat–PCAF interaction. Acetylation at Lys50 creates a new site for binding to PCAF and dictates the formation of a ternary complex of Tat–PCAF–P‐TEFb. Thus, differential lysine acetylation of Tat coordinates the interactions with its co‐activators, cyclin T1 and PCAF. Our results may help in understanding the ordered recruitment of Tat co‐activators to the HIV‐1 promoter.