E1A directly binds and regulates the P/CAF acetyltransferase.
The P/CAF protein has intrinsic histone acetyltransferase (HAT) activity and is capable of binding the transcriptional co-activator CBP. Here we show that P/CAF can regulate transcription and that this function is independent of its binding to CBP. The HAT domain of P/CAF has transcriptional activation potential in yeast. In mammalian cells P/CAF can stimulate transcription of the RSV promoter, using the activity of its HAT domain. We show that the adenovirus protein E1A targets P/CAF and sequesters its transcriptional activity. Binding of E1A to P/CAF is direct, independent of CBP and requires residues within E1A conserved region 1. We find that the P/CAF binding residues in E1A are within a motif shown to be essential for efficient disruption of myogenesis by E1A. The fact that E1A can directly bind and regulate the activity of P/CAF, independently of its regulation of CBP, highlights an important role for P/CAF in the process of cell differentiation.
Wellcome/CRC Institute, Department of Pathology, Cambridge University, UK.
J L
JL
Reid
A J
AJ
Bannister
P
P
Zegerman
M A
MA
Martínez-Balbás
T
T
Kouzarides
D000123:Acetyltransferases / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D017500:Adenovirus E1A Proteins / Q000378:metabolism* / Q000502:physiology; D050882:CREB-Binding Protein; D002460:Cell Line; D004789:Enzyme Activation; D004794:Enzyme Repression; D051548:Histone Acetyltransferases; D006801:Humans; D009687:Nuclear Proteins / Q000502:physiology; D011485:Protein Binding; D012097:Repressor Proteins / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000502:physiology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D017500:Adenovirus E1A Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D000123:Acetyltransferases; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D051548:Histone Acetyltransferases