Differential acetylation of Tat coordinates its interaction with the co-activators cyclin T1 and PCAF.

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.
Mesh Terms:
Acetylation, Acetyltransferases, Blotting, Western, Cell Cycle Proteins, Chromatography, Affinity, Cyclin T, Cyclins, Gene Products, tat, Glutathione Transferase, HIV Long Terminal Repeat, HeLa Cells, Histone Acetyltransferases, Humans, Lysine, Models, Biological, Nuclear Proteins, Peptides, Protein Binding, Recombinant Fusion Proteins, Trans-Activators, Transcription Factors, Transcriptional Activation, p300-CBP Transcription Factors
EMBO J.
Date: Dec. 16, 2002
Download Curated Data For This Publication
170145
Switch View:
  • Interactions 8