TRANSCRIPTIONAL REPRESSION AND P53 DEPENDENT APOPTOSIS

转录抑制和 P53 依赖性细胞凋亡

• 批准号: 6350357
• 负责人: Maureen E. Murphy
• 金额: $ 25.11万
• 依托单位: FOX CHASE CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2004-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6350357
• 关键词: apoptosis; cell line; gene expression; gene induction /repression; gene mutation; genetic promoter element; genetic regulation; genetic transcription; p53 gene /protein; tissue /cell culture; transfection

DESCRIPTION: (adapted verbatim from the investigator's abstract) The p53 tumor suppressor gene continues to hold distinction as the most frequently mutated gene in human cancer. The powerful selection for mutation of p53 in cancer is believed to result from its ability to induce programmed cell death (apoptosis). Evidence from several groups indicates that apoptosis induction by p53 does not rely on its best- characterized activity, transcriptional activation. This proposal seeks to characterize a new activity of p53, sequence-specific transcriptional repression. Wild type (wt) p53 induction in normal and tumor cells leads to transcriptional repression of Map4, which encodes a ubiquitously- expressed microtubule-polymerizing protein. Overexpression of Map4 in cells undergoing p53-dependent apoptosis delays the appearance of dying cells, verifying the importance of this process to apoptosis. In stably- transfected cells, the Map4 promoter can confer negative regulation by p53 to a heterologous gene. A fragment of this promoter can interact with wt but not mutant p53 protein in cell extracts. Recent data indicate that in addition to Map4, p53 represses other genes encoding components of microtubules. Elucidation of the mechanism of transcriptional repression by p53 is likely to be a critical step toward understanding tumor suppression by this protein. Understanding other targets genes of p53-mediated repression will also be important. This proposal seeks to achieve these goals.

描述：（从研究者的摘要逐字改编）p53