Regulation of RCC1 through N-terminal serine metnylation

描述(由申请人提供)：RCC1是小的、RAS样GTP酶RAN的核苷酸交换因子。它参与了许多细胞过程，包括纺锤体组装和纺锤体检查点调节，当调控不当时，可能会导致细胞转化和癌症发生。确定RCC1是如何调控的将更清楚地定义纺锤体组装和检查点调控是如何控制的，并进一步开发针对这些过程的抗癌治疗药物。Macara实验室最近发现了RCC1的一种新的翻译后修饰，即N-末端丝氨酸甲基化，本提案将研究它在RCC1功能调节中的作用。具体目标#1将确定RCC1功能的N-末端丝氨酸甲基化影响的方面以及它如何调节这些功能。具体目标#2将确定负责RCC1 N末端丝氨酸甲基化的甲基转移酶。

DESCRIPTION (provided by applicant): RCC1 is the nucleotide exchange factor for the small, Ras-like GTPase Ran. It is involved in many cellular processes including spindle assembly and spindle checkpoint regulation, that when misregulated can lead to cellular transformation and carcinogenesis. Determining how RCC1 is regulated will more clearly define how spindle assembly and checkpoint regulation are controlled and further the development of anticancer therapeutics targeted against these processes. A novel post-translational modification of RCC1, N-terminal serine methylation, has recently been identified in the Macara lab, and this proposal will examine its role in the regulation of RCC1 function. Specific aim #1 will determine which aspects of RCC1 function N-terminal serine methylation affects and how it regulates these functions. Specific aim #2 will identify the methyltransferase responsible for the N-terminal serine methylation of RCC1.