Tat-controlled protein acetylation.
Human immunodeficiency virus, type 1-encoded transactivator protein Tat is known to be a substrate of and to interact with several nuclear histone acetyltransferases (HATs). Here we show that Tat is a general inhibitor of histone acetylation by cellular HATs and that for at least one of them, the CREB-binding protein (CBP), it induces a substrate selectivity. Indeed, in the presence of Tat, the acetylation of histones by CBP was severely inhibited, while that of p53 and MyoD remained unaffected. The C-terminal domain of Tat, dispensable for the activation of viral transcription, was found to be necessary and sufficient to interfere with histone acetylation. These results demonstrate that Tat is able to selectively modulate cellular protein acetylation by nuclear HATs and therefore to take over this specific signaling system in cells.
Col
Edwige
E
Laboratoire de Biologie Moléculaire et Cellulaire de la Différenciation-INSERM U309, Equipe Chromatine et Expression des Gènes, Institut Albert Bonniot, Faculté de Médecine, Domaine de la Merci, 38706 La Tronche Cedex, France.
Gilquin
Benoit
B
Caron
Cécile
C
Khochbin
Saadi
S
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D050882:CREB-Binding Protein; D018797:Cell Cycle Proteins; D017931:DNA Primers; D015696:Gene Products, tat / Q000378:metabolism*; D017930:Genes, Reporter; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006801:Humans; D019169:Jurkat Cells; D008156:Luciferases / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D050880:p300-CBP Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D050882:CREB-Binding Protein; D018797:Cell Cycle Proteins; D017931:DNA Primers; D015696:Gene Products, tat; D051548:Histone Acetyltransferases; D008156:Luciferases; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D050880:p300-CBP Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D000099224:p300-CBP-Associated Factor; C494363:CREBBP protein, human