期刊
BMB REPORTS
卷 55, 期 2, 页码 92-97出版社
KOREAN SOCIETY BIOCHEMISTRY & MOLECULAR BIOLOGY
DOI: 10.5483/BMBRep.2022.55.2.148
关键词
CK2; JMJD2a; LSD1; p53; Senescence-associated heterochromatin foci
资金
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning [NRF-2015R1A2A2A01004593, NRF-2019R1A2C100 5219]
This study investigated the roles of histone lysine demethylases JMJD2a and LSD1 in CK2 downregulation-mediated senescence. The results showed that CK2 downregulation reduced the expression of JMJD2a and LSD1 by activating mTOR, resulting in H3K9me3 induction. This study suggests that CK2 is a potential therapeutic target for age-related diseases.
Lysine methylation is one of the most important histone modifications that modulate chromatin structure. In the present study, the roles of the histone lysine demethylases JMJD2a and LSD1 in CK2 downregulation-mediated senescence were investigated. The ectopic expression of JMJD2a and LSD1 suppressed the induction of senescence-associated beta-galactosidase activity and heterochromatin foci formation as well as the reduction of colony-forming and cell migration ability mediated by CK2 knockdown. CK2 downregulation inhibited JMJD2a and LSD1 expression by activating the mammalian target of rapamycin (mTOR)-ribosomal p70 S6 kinase (p70S6K) pathway. In addition, the downregulation of JMJD2a and LSD1 was involved in activating the p53-p21(Cip1/WAF1)-SUV39h1-trimethylation of the histone H3 Lys9 (H3K9me3) pathway in CK2-downregulated cells. Further, CK2 downregulation-mediated JMJD2a and LSD1 reduction was found to stimulate the dimethylation of Lys370 on p53 (p53K370me2) and nuclear import of SUV39h1. Therefore, this study indicated that CK2 downregulation reduces JMJD2a and LSD1 expression by activating mTOR, resulting in H3K9me3 induction by increasing the p53K370me2-dependent nuclear import of SUV39h1. These results suggest that CK2 is a potential therapeutic target for age-related diseases.
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