Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Protein Kinase CK2 Is Upregulated by Calorie Restriction and Induces Autophagy

  • Park, Jeong-Woo (School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University) ;
  • Jeong, Jihyeon (School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University) ;
  • Bae, Young-Seuk (School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University)
  • Received : 2021.07.07
  • Accepted : 2021.11.21
  • Published : 2022.03.31
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Abstract

Calorie restriction (CR) and the activation of autophagy extend healthspan by delaying the onset of age-associated diseases in most living organisms. Because protein kinase CK2 (CK2) downregulation induces cellular senescence and nematode aging, we investigated CK2's role in CR and autophagy. This study indicated that CR upregulated CK2's expression, thereby causing SIRT1 and AMP-activated protein kinase (AMPK) activation. CK2α overexpression, including antisense inhibitors of miR-186, miR-216b, miR-337-3p, and miR-760, stimulated autophagy initiation and nucleation markers (increase in ATG5, ATG7, LC3BII, beclin-1, and Ulk1, and decrease in SQSTM1/p62). The SIRT1 deacetylase, AKT, mammalian target of rapamycin (mTOR), AMPK, and forkhead homeobox type O (FoxO) 3a were involved in CK2-mediated autophagy. The treatment with the AKT inhibitor triciribine, the AMPK activator AICAR, or the SIRT1 activator resveratrol rescued a reduction in the expression of lgg-1 (the Caenorhabditis elegans ortholog of LC3B), bec1 (the C. elegans ortholog of beclin-1), and unc-51 (the C. elegans ortholog of Ulk1), mediated by kin-10 (the C. elegans ortholog of CK2β) knockdown in nematodes. Thus, this study indicated that CK2 acted as a positive regulator in CR and autophagy, thereby suggesting that these four miRs' antisense inhibitors can be used as CR mimetics or autophagy inducers.

Keywords

Acknowledgement

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (NRF-2019R1A2C1005219).

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