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KMID : 0624620200530050272
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BMB Reports
2020 Volume.53 No. 5 p.272 ~ p.277
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Protein kinase CK2 activates Nrf2 via autophagic degradation of Keap1 and activation of AMPK in human cancer cells
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Jang Da-Eun
Song Jun-Bin
Park Jeong-Woo
Yoon Soo-Hyun
Bae Young-Seuk
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Abstract
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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 ECHassociated 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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KEYWORD
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AMPK, Antioxidants, CK2, Keap1, Nrf2
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