Reid J L, Bannister A J, Zegerman P, Martínez-Balbás M A, Kouzarides T
Wellcome/CRC Institute, Department of Pathology, Cambridge University, UK.
EMBO J. 1998 Aug 3;17(15):4469-77. doi: 10.1093/emboj/17.15.4469.
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.
P/CAF蛋白具有内在的组蛋白乙酰转移酶（HAT）活性，并且能够结合转录共激活因子CBP。在此我们表明，P/CAF能够调节转录，且该功能独立于其与CBP的结合。P/CAF的HAT结构域在酵母中具有转录激活潜能。在哺乳动物细胞中，P/CAF可利用其HAT结构域的活性刺激劳氏肉瘤病毒（RSV）启动子的转录。我们表明，腺病毒蛋白E1A靶向P/CAF并抑制其转录活性。E1A与P/CAF的结合是直接的，不依赖于CBP，且需要E1A保守区域1内的残基。我们发现，E1A中与P/CAF结合的残基位于一个对E1A有效破坏肌细胞生成至关重要的基序内。E1A能够直接结合并调节P/CAF的活性，且独立于其对CBP的调节，这一事实凸显了P/CAF在细胞分化过程中的重要作用。
