SAMHD1 acetylation enhances its deoxynucleotide triphosphohydrolase activity and promotes cancer cell proliferation
| Autor: | Ji Hae Seo, Se Hwan Jang, Eun Lee, Soo Hyung Ryu, Ensil Yu, Jeong A. Kim, Sunho An, Hoang Le, Hee-Jun Wee, Zee Yong Park, Kyu Won Kim, Ji-Hyeon Park, Tam Thuy Lu Vo, Hye Shin Lee, Myoung-Kuk Jang, Sung-Jin Bae, Danbi Lee, Young-Hwa Chung |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
dNTPase business.industry Lysine Wild type Cell cycle SAMHD1 Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Oncology Acetylation 030220 oncology & carcinogenesis Cancer cell cancer Medicine cell cycle business HD domain Intracellular Research Paper acetylation |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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