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
Log in using your username and password
Log in through your institution
Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$30.00 .
Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.
Article navigation
Related articles
Cited by...
More in this TOC section
Similar articles
Subject collections
Other journals from The Company of Biologists
Introducing FocalPlane’s new Community Manager, Esperanza Agullo-Pascual
We are pleased to welcome Esperanza to the Journal of Cell Science team. The new Community Manager for FocalPlane, Esperanza is joining us from the Microscopy Core at Mount Sinai School of Medicine. Find out more about Esperanza in her introductory post over on FocalPlane.
New funding scheme supports sustainable events
As part of our Sustainable Conferencing Initiative, we are pleased to announce funding for organisers that seek to reduce the environmental footprint of their event. The next deadline to apply for a Scientific Meeting grant is 26 March 2021.
Read & Publish participation continues to grow
"Alongside pre-printing for early documentation of work, such mechanisms are particularly helpful for early-career researchers like me.”
Dr Chris MacDonald (University of York) shares his experience of publishing Open Access as part of our growing Read & Publish initiative. We now have over 150 institutions in 15 countries and four library consortia taking part – find out more and view our full list of participating institutions.
Cell scientist to watch: Romain Levayer
In an interview, Romain Levayer talks about starting his own lab, his love for preprints and his experience of balancing parenting with his research goals.
Live lactating mammary tissue
In a stunning video, Stewart et al. demonstrate warping of the alveolar unit due to basal cell-generated force as part of their recent work investigating roles for mechanically activated ion channels in lactation and involution.
Visit our YouTube channel to watch more videos from JCS, our sister journals and the Company.
JCS and COVID-19
For more information on measures Journal of Cell Science is taking to support the community during the COVID-19 pandemic, please see here.
If you have any questions or concerns, please do not hestiate to contact the Editorial Office.