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 对整个生物体构成威胁。因此，这些基因的激活必须受到巧妙的调控，因为 它们必须只有在特殊情况下才能激活。我的建议的目标是理解 P53对应激的转录反应机制及其在影响细胞周期中的作用 细胞的命运。具体目标如下：1.转录因子的组成和功能是什么 机制组装时对细胞周期停滞和促凋亡的p53靶基因的反应 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 应对压力的决定？3.p63和p73的各种剪接变体在 应激激活调控P53靶基因？此信息对于详细的 了解P53如何能够调节应激反应，并将有助于新的 各种癌症的治疗方法。

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.