MARC Predoctoral Fellowship

p53对细胞周期和凋亡基因的激活在控制或消除可能 会对整个生物体造成威胁。因此，这些基因的激活必须受到巧妙的调控， 它们只能在特殊情况下激活。我的建议的目的是了解 p53对应激的转录反应机制以及这一机制如何在影响应激反应中发挥作用。 细胞命运具体目标如下：1.转录因子的组成和功能是什么 当组装在细胞周期停滞和促凋亡p53靶基因上时， 压力？2.哪些p53辅因子（包括修饰p53的酶）是帮助细胞命运所必需的 压力下的决定吗3. p63和p73的各种剪接变异体在肿瘤的发生中起什么作用？ 来强调p53靶基因的激活调节？这些信息对于详细的 了解p53如何能够介导应激反应，并将有助于开发新的 治疗各种癌症。

The activation of cell cycle and apoptotic genes by p53 is crucial in controlling or eliminating cells that may be a threat to the whole organism. The activation of these genes must therefore be cleverly regulated since they must only be activated under exceptionalcircumstances. The goal of my proposal is to understand the mechanisms of the transcriptional response to stress by p53 and how this may play a role in influencing the cells fate. The specific aims are as follows: 1. What is the composition and function of the transcriptional machinery when assembled on cell cycle arrest and pro-apoptotic p53 target genes in response to various stresses? 2. Which p53 cofactors (including enzymes that modify p53)are required to aid in cell fate decisions in response to stress? 3. What role do the various splice variants of p63 and p73 play with regards to stress activated regulation of p53 target genes? This information will be critical for a detailed understanding of how p53 is able to mediate stress responses and will aid in the development of new therapies for various cancers.