Handling Editor: Michael Way
ABSTRACT
Vaccinia-related kinase 3 (VRK3) has been reported to be a negative regulator of ERK (ERK1 and ERK2; also known as MAPK3 and MAPK1, respectively) that protects cells from persistent ERK activation and inhibits ERK-dependent apoptosis. Here we report that the E3 ubiquitin–protein ligase RNF144a promotes the degradation of VRK3 via polyubiquitylation and thus affects VRK3-mediated ERK activity. Under oxidative stress, VRK3 migrates from the nucleus to the cytoplasm, which increases its chance of interacting with RNF144a, thereby promoting the degradation of VRK3. Overexpression of RNF144a increases ERK activity via downregulation of VRK3 and promotes ERK-dependent apoptosis. In contrast, depletion of RNF144a increases the protein level of VRK3 and protects cells from excessive ERK activity. These findings suggest that VRK3 protects cells by suppressing oxidative stress-induced ERK, and that RNF144a sensitively regulates this process.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: S.H.H., K.-T.K.; Methodology: S.H.H.; Validation: S.H.H., K.-T.K.; Formal analysis: S.H.H.; Investigation: S.H.H., K.-T.K.; Resources: S.H.H., K.-T.K.; Writing - original draft: S.H.H., K.-T.K.; Writing - review & editing: S.H.H., K.-T.K.; Supervision: K.-T.K.; Project administration: S.H.H., K.-T.K.; Funding acquisition: K.-T.K.
Funding
This study was supported by BK21 Plus funded by the Ministry of Education (10Z20130012243), the Bio & Medical Technology Development Program of the National Research Foundation of Korea (2017M3C7A1023478), the Cooperative Research Program for Agriculture Science and Technology Development of the Rural Development Administration (Project No. PJ01324801), and the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (2019R1A2C2009440).
Supplementary information
Supplementary information available online at https://jcs.biologists.org/lookup/doi/10.1242/jcs.247304.supplemental
- Received April 7, 2020.
- Accepted September 17, 2020.
- © 2020. Published by The Company of Biologists Ltd
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