Hupp T R, Sparks A, Lane D P
Department of Biochemistry, Dundee University, Scotland.
Cell. 1995 Oct 20;83(2):237-45. doi: 10.1016/0092-8674(95)90165-5.
Normal cells contain p53 protein in a latent state that can be activated for sequence-specific transcription by low levels of UV radiation without an increase in protein levels. Microinjection of cells with an antibody specific to the C-terminal negative regulatory domain can activate the function of p53 as a specific transcription factor in the absence of irradiation damage, suggesting that posttranslational modification of a negative regulatory domain in vivo is a rate-limiting step for p53 activation. Small peptides derived from the negative regulatory domain of p53 have been used as biochemical tools to distinguish between allosteric and steric mechanisms of negative regulation of p53 tetramer activity. Presented is the development of a highly specific peptide activation system that is consistent with an allosteric mechanism of negative regulation and that forms a precedent for the synthesis of novel low molecular mass modifiers of the p53 response.
正常细胞中含有处于潜伏状态的p53蛋白，在低水平紫外线辐射下，该蛋白无需蛋白质水平增加就能被激活进行序列特异性转录。用针对C末端负调控域的特异性抗体对细胞进行显微注射，可在无辐射损伤的情况下激活p53作为特异性转录因子的功能，这表明体内负调控域的翻译后修饰是p53激活的限速步骤。源自p53负调控域的小肽已被用作生化工具，以区分p53四聚体活性负调控的变构和空间机制。本文介绍了一种高度特异性的肽激活系统的开发，该系统与负调控的变构机制一致，为合成新型p53反应低分子量调节剂开创了先例。
