Protein kinase CK2 activates Nrf2 via autophagic degradation of Keap1 and activation of AMPK in human cancer cells

• Published in: BMB reports Vol. 53; no. 5; pp. 272 - 277
• Main Authors: Jang, Da Eun, Song, Junbin, Park, Jeong-Woo, Yoon, Soo-Hyun, Bae, Young-Seuk
• Format: Journal Article
• Language: Korean
• Published: 생화학분자생물학회 31.05.2020
• Subjects: AMPK; Antioxidants; CK2; Keap1; Nrf2; Antioxidants; Keap1; AMPK; CK2; Nrf2
• ISSN: 1976-6696; 1976-670X

Protein kinase CK2 downregulation induces premature senescence in various human cell types via activation of the reactive oxygen species (ROS)-p53-p21 Cip1/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-p21 Cip1/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. [BMB Reports 2020; 53(5): 272-277]