Regulation of RCC1 through N-terminal serine metnylation

描述（由申请方提供）：RCC 1是小Ras样GTdR Ran的核苷酸交换因子。它参与许多细胞过程，包括纺锤体组装和纺锤体检查点调节，当其被错误调节时可导致细胞转化和癌变。确定RCC 1是如何调节的将更清楚地定义纺锤体组装和检查点调节是如何控制的，并进一步开发针对这些过程的抗癌疗法。一种新的翻译后修饰的RCC 1，N-末端丝氨酸甲基化，最近已被确定在Macara实验室，该提案将检查其在RCC 1功能的调节作用。具体目标#1将确定RCC 1功能的哪些方面N-末端丝氨酸甲基化影响以及它如何调节这些功能。具体目标#2将鉴定负责RCC 1的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.