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.
Brès
Vanessa
V
Laboratoire de Virologie Moléculaire et Transfert de Gène, Institut de Génétique Humaine, CNRS UPR1142, Montpellier, France.
Tagami
Hideaki
H
Péloponèse
Jean-Marie
JM
Loret
Erwan
E
Jeang
Kuan-Teh
KT
Nakatani
Yoshihiro
Y
Emiliani
Stephane
S
Benkirane
Monsef
M
Kiernan
Rosemary E
RE
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002846:Chromatography, Affinity; D056906:Cyclin T; D016213:Cyclins / Q000378:metabolism*; D015696:Gene Products, tat / Q000737:chemistry* / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D016325:HIV Long Terminal Repeat; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006801:Humans; D008239:Lysine / Q000737:chemistry; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D015533:Transcriptional Activation; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D056906:Cyclin T; D016213:Cyclins; D015696:Gene Products, tat; D005982:Glutathione Transferase; D051548:Histone Acetyltransferases; D008239:Lysine; D009687:Nuclear Proteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C503684:CCNT1 protein, human