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Role of SAMHD1 acetylation in its dNTPase activity and cancer cell proliferation : SAMHD1 아세틸화가 뉴클레오티드3인산 분해능과 암세포 분열에 미치는 영향 연구
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- Authors
- Advisor
- 김규원
- Major
- 약학대학 약학과
- Issue Date
- 2017-08
- Publisher
- 서울대학교 대학원
- Description
- 학위논문 (박사)-- 서울대학교 대학원 약학대학 약학과, 2017. 8. 김규원.
- Abstract
- SAMHD1 is a deoxynucleotide triphosphohydrolase (dNTPase) which inhibits retroviruses by depleting intracellular deoxynucleotide triphosphates (dNTPs) in noncycling myeloid cells. Although SAMHD1 is expressed ubiquitously throughout the human body, the molecular mechanism to directly regulate its enzymatic activity and its function in non-immune cells are relatively unexplored. Here, I demonstrate that the dNTPase activity of SAMHD1 is regulated by acetylation, which promotes cell cycle progression in cancer cells. SAMHD1 was acetylated at residue K405 by ARD1, an acetyltransferase, which directly enhanced its dNTPase activity in vitro. When SAMHD1 wildtype and non-acetylated K405R mutant overexpressing stable cells were constructed in cancer cells, K405R mutant expressing cells showed decreased G1/S transition and slower proliferation over wildtype cells. SAMHD1 acetylation level was strongest during the G1 phase, implicating its role during G1 phase. Collectively, these findings suggest that SAMHD1 acetylation enhances its dNTPase activity and promotes cancer cell proliferation.
- Language
- English
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