INFECTIOUS DNA FOR ENDOGENOUS RNA TUMOR VIRUS GENES

描述：这个项目的总体目标是阐明 控制细胞存活的细胞内信号通路，通过阻止 细胞凋亡。在上一个资助期，申请人发现 几种细胞生长因子依赖的生存需要PI3激酶 类型。这些观察结果得到了扩展，因为它证明了 丝氨酸/苏氨酸蛋白激酶Akt是细胞内PI3蛋白的关键下游效应因子 生存之路。进一步研究表明，细胞凋亡是由 生长因子剥夺或抑制PI3激酶受以下因素调节 Bcl2家族成员与ICE家族蛋白的激活。在……里面 此外，癌蛋白MDM2已被确定为一种新的底物 ICE家族的蛋白水解酶及其降解作用可能有助于 通过解除对P53的调控而导致的细胞凋亡。申请人提议在此基础上 这些观察具有以下四个具体目标。(一)确定 作为Akt唯一已知的生理底物，GSK3是否参与了 调节细胞的生存。(2)分析PI3激酶诱导的作用 向BCL2家族的成员发送信号。(3)勾勒出 冰上蛋白水解酶受PI3激酶信号调控并确定Akt 或者下游的信号分子作用于控制蛋白酶的激活。(4) 确定MDM2被细胞凋亡蛋白酶切的生物学作用 细胞死亡途径。

DESCRIPTION: The overall goal of this project is to elucidate the intracellular signalling pathways that control cell survival by preventing apoptosis. In the previous funding period, the applicant discovered that PI3 kinase was required for growth factor-dependent survival of several cell types. These observations were extended by the demonstration that the Ser/Thr kinase Akt is a key downstream effector of PI3 kinase in the cell survival pathway. Further studies have shown that apoptosis resulting from growth factor deprivation or inhibition of PI3 kinase is regulated by members of the Bcl-2 family and activation of ICE family proteases. In addition the oncoprotein MDM2 has been identified as a novel substrate for ICE family proteases and its proteolytic degradation may contribute to apoptosis by deregulation of p53. The applicant proposes to build upon these observations with the following four specific aims. (1) To determine whether GSK3, the only known physiological substrate of Akt, is involved in regulating cell survival. (2) To analyze the effects of PI3 kinase-induced signalling on members of the Bcl2 family. (3) To delineate the cascade of ICE proteases regulated by PI3 kinase signals and to determine whether Akt or downstream signalling molecules act to control protease activation. (4) To determine the biological role of MDM2 cleavage by apoptotic proteases in the cell death pathway.