REGULATION OF P53 FUNCTION BY SV40 T ANTIGEN

通过诱变改变p53基因产物的功能 会导致正常细胞癌变。几种病毒，包括 SV40，编码与p53结合的基因产物，可能是为了颠覆其 正常发挥肿瘤抑制因子的作用。将在以下方面实现几个目标 目的：研究P53的结构和功能及其调控机制。 SV40T抗原。(1)P53的DNA结合特性将是 研究目的是为了了解(I)它所针对的DNA序列 结合，(Ii)它接触DNA的方式和(Iii) 与DNA结合所必需的P53蛋白。(2)P53的作用 将对转录激活剂进行调查。P53基因表达的能力 单独或与其他转录一起调节转录 我们将对各种因素进行考察。(3)P53抑制DNA的能力 复制，通过结合SV40T抗原或通过结合DNA，将是 在体外和体内都有特征。(4)SV40T抗原， 单独或当与Rb蛋白结合时，抑制DNA结合 并将研究P53的转录激活特性。(5) 与P53结合并在功能上相互作用的细胞蛋白将是 已确认身份。(6)非洲爪哇P53蛋白在卵母细胞中的性质和作用 并对早期胚胎进行检查。希望对这一事件的洞察 病毒肿瘤抗原和细胞肿瘤抑制因子的功能将是 收获了。

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.