S-Space College of Natural Sciences (자연과학대학) Dept. of Biological Sciences (생명과학부) Theses (Master's Degree_생명과학부)
Role of CHIP-mediated ubiquitination of katanin p60 on neuronal development : CHIP에 의해 매개되는 katanin p60의 유비퀴틴화가 신경세포 성장에 미치는 영향에 관한 연구
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- 서울대학교 대학원
- 학위논문 (석사)-- 서울대학교 대학원 : 생명과학부, 2012. 2. 정진하.
- Katanin p60 is the catalytic subunit of katanin that severs and disassembles microtubule, thus controlling various microtubule-associated processes, such as meiosis. In neuronal cells, katanin p60 enhances axonal outgrowth and branching of dendrites, thereby promoting the development of neuronal cells. Thus, the factors affecting katanin p60 stability would largely influence the neuronal development. In this study, I show that CHIP (carboxyl terminus of HSP70-interacting protein) plays an important role in the control of katanin p60 stability, and thereby in regulation of neuronal development. CHIP interacted katanin p60 by using HSP90 as an adaptor. Specifically, the AAA domain of katanin p60 interacted with HSP90, which in turn binds to the TPR (tetratricopeptide repeat) domain of CHIP. Consistently, CHIP ubiquitinated and destabilized katanin p60 by mediating its proteasome-dependent degradation. Moreover, expression of CHIP in primary hippocampal neuronal cells, but not its catalytically inactive mutant (in which His260 was replaced by Gln), decreased the length and number of neuritis. These results suggest that CHIP plays a critical role in negative regulation of the development of neuronal cells by down-regulating the stability of katanin p60.
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