2. Academic Validation
  3. Rapid phosphorylation of glucose-6-phosphate dehydrogenase by casein kinase 2 sustains redox homeostasis under ionizing radiation

Rapid phosphorylation of glucose-6-phosphate dehydrogenase by casein kinase 2 sustains redox homeostasis under ionizing radiation

  • Redox Biol. 2023 Sep:65:102810. doi: 10.1016/j.redox.2023.102810.
Yilong Hao 1,  Tao Ren 2,  Xiaoke Huang 3,  Mi Li 4,  Jong-Ho Lee 5,  Qianming Chen 6,  Rui Liu 7,  Qingfeng Tang 8
Affiliations

Affiliations

  • 1 Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, PR China.
  • 2 Oncology Department (Key Clinical Specialty of Sichuan Province), The First Affiliated Hospital of Chengdu Medical College, Chengdu, 610500, PR China.
  • 3 Department of Urology, Xindu District People's Hospital of Chengdu, Chengdu, 610500, China.
  • 4 Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • 5 Department of Health Sciences, The Graduated School of Dong-A University, Busan, 49315, Republic of Korea.
  • 6 Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, PR China. Electronic address: [email protected].
  • 7 State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, PR China. Electronic address: [email protected].
  • 8 Department of Urology, Xindu District People's Hospital of Chengdu, Chengdu, 610500, China. Electronic address: [email protected].
PMID: 37478541 DOI: 10.1016/j.redox.2023.102810
Abstract

Exposure to ionizing radiation leads to oxidative damages in living cells. NADPH provides the indispensable reducing power to regenerate the reduced glutathione to maintain cellular redox equilibria. In mammalian cells, pentose phosphate pathway (PPP) is the major route to produce NADPH by using glycolytic intermediates, and the rate-limiting step of PPP is controlled by glucose-6-phosphate dehydrogenase (G6PD). Nevertheless, whether G6PD is timely co-opted under ionizing radiation to cope with oxidative stress remains elusive. Here we show that cellular G6PD activity is induced 30 min after ionizing radiation, while its protein expression is mostly unchanged. Mechanistically, Casein Kinase 2 (CK2) phosphorylates G6PD T145 under ionizing radiation, which consolidates the enzymatic activity of G6PD by facilitating G6PD binding with its substrate NADP+. Further, CK2-dependent G6PD T145 phosphorylation promotes NADPH production, decreases ROS level and supports cell proliferation under ionizing radiation. Our findings report a new anti-oxidative signaling route under ionizing radiation, by which CK2-mediated rapid activation of G6PD orchestrates NADPH synthesis to maintain redox homeostasis, thereby highlighting its potential value in the early treatment of ionizing radiation-induced injuries.

Keywords

CK2; G6PD; Ionizing radiation; NADPH; Oxidative stress.

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