REGULATION OF P53 FUNCTION BY SV40 T ANTIGEN

通过诱变改变p53基因产物的功能 导致正常细胞癌变 几种病毒，包括 SV40，编码与p53结合的基因产物，可能是为了破坏其功能。 作为肿瘤抑制剂的正常功能。 将追求几个目标， 为了研究p53蛋白的结构和功能， SV40 T抗原。(1)p53的DNA结合特性将是 （一）研究目的是为了了解（一）DNA序列， 结合，（ii）其接触DNA的模式，以及（iii） p53蛋白是与DNA结合所必需的。(2)p53的作用 将研究转录激活剂。 p53的功能 单独调节转录或与其它转录协同调节 将审查各种因素。(3)p53抑制DNA的能力 通过与SV40 T抗原结合或通过与DNA结合的复制，将被 在体外和体内表征。(4)SV40 T抗原， 单独或与RB蛋白结合时，抑制DNA结合 并将研究p53的转录激活特性。（五） 与p53结合并在功能上相互作用的细胞蛋白质将被 鉴定(6)非洲爪蟾卵母细胞中p53蛋白的性质和作用 早期胚胎将被检查。 人们希望， 病毒肿瘤抗原和细胞肿瘤抑制因子的功能将被 获得。

Alteration of the function of the p53 gene product through mutagenesis causes normal cells to become cancerous. Several viruses, including SV40, encode gene products that bind to p53, presumably to subvert its normal function as a tumor suppressor. Several aims will be pursued in order to study the structure and function of p53 and their regulation by SV40 T antigen. (1) The DNA binding properties of p53 will be investigated in order to understand (i) the DNA sequences to which it binds, (ii) the mode by which it contacts DNA and (iii) the region of the p53 protein that is necessary for binding to DNA. (2) The role of p53 as a transcriptional activator will be investigated. The ability of p53 to regulate transcription alone or in concert with other transcription factors will be examined. (3) The ability of p53 to inhibit DNA replication, by binding to SV40 T antigen or by binding to DNA, will be characterized in vitro and in vivo. (4) The mode by which SV40 T antigen, either alone or when bound to the RB protein, represses the DNA binding and transcriptional activation properties of p53 will be studied. (5) Cellular proteins that bind to and interact functionally with p53 will be identified. (6) The properties and role of Xenopus laevis p53 in oocytes and early embryos will be examined. It is hoped that insight into the functions of viral tumor antigens and cellular tumor suppressors will be gained.