Research Papers:

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

Eun Ji Lee, Ji Hae Seo, Ji-Hyeon Park, Tam Thuy Lu Vo, Sunho An, Sung-Jin Bae, Hoang Le, Hye Shin Lee, Hee-Jun Wee, Danbi Lee, Young-Hwa Chung, Jeong A. Kim, Myoung-Kuk Jang, Soo Hyung Ryu, Ensil Yu, Se Hwan Jang, Zee Yong Park and Kyu-Won Kim _

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Oncotarget. 2017; 8:68517-68529. https://doi.org/10.18632/oncotarget.19704

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Eun Ji Lee1, Ji Hae Seo2, Ji-Hyeon Park1, Tam Thuy Lu Vo1, Sunho An1, Sung-Jin Bae1, Hoang Le1, Hye Shin Lee1, Hee-Jun Wee1, Danbi Lee3, Young-Hwa Chung3, Jeong A. Kim4, Myoung-Kuk Jang5, Soo Hyung Ryu6, Ensil Yu7, Se Hwan Jang8, Zee Yong Park8 and Kyu-Won Kim1,9

1SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea

2Department of Biochemistry, Keimyung University School of Medicine, Daegu 42601, Korea

3Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea

4DNA Link Inc., Seoul 03759, Korea

5Department of Internal Medicine, Hallym University College of Medicine, Kangdong Sacred Heart Hospital, Seoul 05355, Korea

6Department of Internal Medicine, Inje University College of Medicine, Seoul Paik Hospital, Seoul 04551, Korea

7Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea

8School of Life Sciences, Gwangju Institute of Science & Technology, Gwangju 61005, Korea

9Crop Biotechnology Institute, GreenBio Science and Technology, Seoul National University, Pyeongchang 25354, Korea

Correspondence to:

Kyu-Won Kim, email: [email protected]

Keywords: SAMHD1, acetylation, dNTPase, cell cycle, cancer

Received: April 19, 2017     Accepted: June 28, 2017     Published: July 31, 2017


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.

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