Components of Ras-mediated growth control

描述（由申请人提供）：Ras家族gtpase是控制细胞增殖、分化和细胞存活的细胞调节系统的关键组成部分。这些系统的不当调控直接导致人类癌症的发生和发展。该建议旨在解码Ras家族GTPases参与的细胞调节网络的组成、组织和功能。我们的重点是分离分子支点，这些支点可以用来转移致癌ras诱导的细胞增殖和生存限制的腐败。我们的具体目标是：1)TBK1作为致癌Ras相关癌症的肿瘤靶点的机制阐述；2)全基因组RNAi筛选基质分析捕获致癌Ras合成致死位点；3)人类kinome与EGF受体信号的综合定位。

DESCRIPTION (provided by applicant): Ras family GTPases are critical components of cell regulatory systems that control proliferation, differentiation, and cell survival. Inappropriate regulation of these systems directly contributes to initiation and progression of human cancer. This proposal is directed at decoding the composition, organization, and function of cell regulatory networks engaged by Ras family GTPases. Our focus is on isolation of molecular fulcrums that can be exploited to deflect oncogenic Ras-induced corruption of cell proliferation and survival restraints. Our specific aims are 1) mechanistic elaboration of TBK1 as an oncology target in oncogenic Ras associated cancers; 2) capture of oncogenic Ras synthetic-lethal loci by matrix analysis of pangenomic RNAi screens; and 3) comprehensive mapping of the human kinome to EGF receptor signaling.