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Research Article
RNF144a induces ERK-dependent cell death under oxidative stress via downregulation of vaccinia-related kinase 3
Seung Hyun Han, Kyong-Tai Kim
Journal of Cell Science 2020 133: jcs247304 doi: 10.1242/jcs.247304 Published 9 November 2020
Seung Hyun Han
Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 37673, Republic of Korea
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  • ORCID record for Seung Hyun Han
Kyong-Tai Kim
Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 37673, Republic of Korea
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  • ORCID record for Kyong-Tai Kim
  • For correspondence: ktk@postech.ac.kr

Handling Editor: Michael Way

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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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Keywords

  • ERK signaling
  • Oxidative stress
  • Proteasomal degradation
  • RNF144a
  • VRK3

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Research Article
RNF144a induces ERK-dependent cell death under oxidative stress via downregulation of vaccinia-related kinase 3
Seung Hyun Han, Kyong-Tai Kim
Journal of Cell Science 2020 133: jcs247304 doi: 10.1242/jcs.247304 Published 9 November 2020
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Research Article
RNF144a induces ERK-dependent cell death under oxidative stress via downregulation of vaccinia-related kinase 3
Seung Hyun Han, Kyong-Tai Kim
Journal of Cell Science 2020 133: jcs247304 doi: 10.1242/jcs.247304 Published 9 November 2020

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