Protein kinase CK2 activates Nrf2 via autophagic degradation of Keap1 and activation of AMPK in human cancer cells.
BMB Rep
; 53(5): 272-277, 2020 May.
Article
in En
| MEDLINE
| ID: mdl-32317087
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-ß-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. [BMB Reports 2020; 53(5) 272-277].
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autophagy
/
Casein Kinase II
/
NF-E2-Related Factor 2
/
AMP-Activated Protein Kinases
/
Kelch-Like ECH-Associated Protein 1
Limits:
Humans
Language:
En
Journal:
BMB Rep
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Year:
2020
Document type:
Article