Chan H M, La Thangue N B
Division of Biochemistry and Molecular Biology, Davidson Building, University of Glasgow, Glasgow, G12 8QQ, UK.
J Cell Sci. 2001 Jul;114(Pt 13):2363-73. doi: 10.1242/jcs.114.13.2363.
p300/CBP transcriptional co-activator proteins play a central role in co-ordinating and integrating multiple signal-dependent events with the transcription apparatus, allowing the appropriate level of gene activity to occur in response to diverse physiological cues that influence, for example, proliferation, differentiation and apoptosis. p300/CBP activity can be under aberrant control in human disease, particularly in cancer, which may inactivate a p300/CBP tumour-suppressor-like activity. The transcription regulating-properties of p300 and CBP appear to be exerted through multiple mechanisms. They act as protein bridges, thereby connecting different sequence-specific transcription factors to the transcription apparatus. Providing a protein scaffold upon which to build a multicomponent transcriptional regulatory complex is likely to be an important feature of p300/CBP control. Another key property is the presence of histone acetyltransferase (HAT) activity, which endows p300/CBP with the capacity to influence chromatin activity by modulating nucleosomal histones. Other proteins, including the p53 tumour suppressor, are targets for acetylation by p300/CBP. With the current intense level of research activity, p300/CBP will continue to be in the limelight and, we can be confident, yield new and important information on fundamental processes involved in transcriptional control.
p300/CBP转录共激活蛋白在协调和整合多个信号依赖事件与转录装置方面发挥着核心作用，使基因活性能够在响应多种生理信号（如影响增殖、分化和凋亡的信号）时达到适当水平。在人类疾病中，特别是在癌症中，p300/CBP的活性可能受到异常调控，这可能会使p300/CBP类似肿瘤抑制因子的活性失活。p300和CBP的转录调节特性似乎是通过多种机制发挥作用的。它们充当蛋白质桥梁，从而将不同的序列特异性转录因子与转录装置连接起来。提供一个构建多组分转录调节复合物的蛋白质支架可能是p300/CBP调控的一个重要特征。另一个关键特性是组蛋白乙酰转移酶（HAT）活性的存在，这赋予了p300/CBP通过调节核小体组蛋白来影响染色质活性的能力。其他蛋白质，包括p53肿瘤抑制因子，也是p300/CBP乙酰化的靶点。随着当前研究活动的高强度开展，p300/CBP将继续备受关注，而且我们可以确信，它将产生有关转录控制基本过程的新的重要信息。
