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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Protein kinase CK2 activates Nrf2 via autophagic degradation of Keap1 and activation of AMPK in human cancer cells

  • Jang, Da Eun (School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University) ;
  • Song, Junbin (School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University) ;
  • Park, Jeong-Woo (School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University) ;
  • Yoon, Soo-Hyun (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University) ;
  • Bae, Young-Seuk (School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University)
  • Received : 2020.02.25
  • Accepted : 2020.03.31
  • Published : 2020.05.31
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Abstract

Protein kinase CK2 downregulation induces premature senescence in various human cell types via activation of the reactive oxygen species (ROS)-p53-p21Cip1/WAF1 pathway. The transcription factor "nuclear factor erythroid 2-related factor 2" (Nrf2) plays an important role in maintaining intracellular redox homeostasis. In this study, Nrf2 overexpression attenuated CK2 downregulation-induced ROS production and senescence markers including SA-β-gal staining and activation of p53-p21Cip1/WAF1 in human breast (MCF-7) and colon (HCT116) cancer cells. CK2 downregulation reduced the transcription of Nrf2 target genes, such as glutathione S-transferase, glutathione peroxidase 2, and glutathione reductase 1. Furthermore, CK2 downregulation destabilized Nrf2 protein via inhibiting autophagic degradation of Kelch-like ECH-associated protein 1 (Keap1). Finally, CK2 downregulation decreased the nuclear import of Nrf2 by deactivating AMP-activated protein kinase (AMPK). Collectively, our data suggest that both Keap1 stabilization and AMPK inactivation are associated with decreased activity of Nrf2 in CK2 downregulation-induced cellular senescence.

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References

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