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SAMHD1 acetylation enhances its deoxynucleotide triphosphohydrolase activity and promotes cancer cell proliferation

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Author(s)
Eun Ji LeeJi Hae SeoJi-Hyeon ParkTam Thuy Lu VoSunho AnSung-Jin BaeHoang LeHye Shin LeeHee-Jun WeeDanbi LeeYoung-Hwa ChungJeong A. KimMyoung-Kuk JangSoo Hyung RyuEnsil YuSe Hwan Jang8, Zee Yong ParkKyu-Won Kim
Keimyung Author(s)
Seo, Ji Hye
Department
Dept. of Biochemistry (생화학)
Journal Title
Oncotarget
Issued Date
2017
Volume
8
Issue
40
Keyword
SAMHD1acetylationcancercell cycledNTPase
Abstract
SAM domain and HD domain containing protein 1 (SAMHD1) is a deoxynucleotide triphosphohydrolase (dNTPase) that inhibits retroviruses by depleting intracellular deoxynucleotide triphosphates (dNTPs) in non-cycling myeloid cells. Although SAMHD1 is expressed ubiquitously throughout the human body, the molecular mechanisms regulating its enzymatic activity and function in non-immune cells are relatively unexplored. Here, we demonstrate that the dNTPase activity of SAMHD1 is regulated by acetylation, which promotes cell cycle progression in cancer cells. SAMHD1 is acetylated at residue lysine 405 (K405) in vitro and in vivo by an acetylatransferase, arrest defective protein 1 (ARD1). Acetylated SAMHD1 wildtype proteins have enhanced dNTPase activity in vitro, whereas non-acetylated arginine substituted mutants (K405R) do not. K405R mutant expressing cancer cells have reduced G1/S transition and slower proliferation compared to wildtype. SAMHD1 acetylation levels are strongest during the G1 phase, indicating a role during G1 phase. Collectively, these findings suggest that SAMHD1 acetylation enhances its dNTPase activity and promotes cancer cell proliferation. Therefore, SAMHD1 acetylation may be a potent therapeutic target for cancer treatment.
Keimyung Author(s)(Kor)
서지혜
Publisher
School of Medicine (의과대학)
Citation
Eun Ji Lee et al. (2017). SAMHD1 acetylation enhances its deoxynucleotide triphosphohydrolase activity and promotes cancer cell proliferation. Oncotarget, 8(40), 68517–68529. doi: 10.18632/oncotarget.19704
Type
Article
ISSN
1949-2553
DOI
10.18632/oncotarget.19704
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/41461
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Biochemistry (생화학)
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