Trends Cell Biol. 1997 Jun;7(6):230-6. doi: 10.1016/S0962-8924(97)01048-9.
Studies on the mechanisms through which the oncogene products of DNA tumour viruses subvert the physiological processes that control cell proliferation have yielded many important insights into the mammalian cell cycle. In the case of the adenovirus E1a oncoprotein, a number of distinct protein domains are required for it to exert its growth-promoting effects. These domains allow E1a to associate physically with and inactivate cellular proteins that normally restrain proliferation. Recently, a group of E1a-interacting proteins discovered in part through studies on viral oncoproteins has become a major focus of research activity. Members of this family, known as p300/CBP, function to regulate transcription and chromatin, and thereby enable diverse signals, particularly those that facilitate differentiation, to be integrated and coordinated with gene expression. Furthermore, accumulating evidence connects genes encoding p300/CBP with diseases such as cancer.
对致癌基因产物通过何种机制颠覆控制细胞增殖的生理过程的研究,使人们对哺乳动物细胞周期有了许多重要的认识。以腺病毒 E1a 癌蛋白为例,其发挥促进生长的效应需要多个不同的蛋白结构域。这些结构域使 E1a 能够与正常抑制增殖的细胞蛋白发生物理性结合,并使其失活。最近,在研究病毒致癌蛋白的过程中发现了一组与 E1a 相互作用的蛋白,这已成为研究活动的一个主要焦点。这个家族的成员被称为 p300/CBP,其功能是调节转录和染色质,从而使各种信号,特别是那些促进分化的信号,与基因表达相整合和协调。此外,越来越多的证据将编码 p300/CBP 的基因与癌症等疾病联系起来。