Cargando…
Nitration-induced ubiquitination and degradation control quality of ERK1
The mitogen-activated protein kinase ERK1/2 (ERKs, extracellular-regulated protein kinases) plays important roles in a wide spectrum of cellular processes and have been implicated in many disease states. The spatiotemporal regulation of ERK activity has been extensively studied. However, scarce info...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604951/ https://www.ncbi.nlm.nih.gov/pubmed/31196894 http://dx.doi.org/10.1042/BCJ20190240 |
_version_ | 1783431775185272832 |
---|---|
author | Zhang, Yuanya Huang, Xiahe Wang, Jinlong Wang, Xiaorong Liu, Xiaofei Chen, Yuhang Xu, Wu Wang, Yingchun |
author_facet | Zhang, Yuanya Huang, Xiahe Wang, Jinlong Wang, Xiaorong Liu, Xiaofei Chen, Yuhang Xu, Wu Wang, Yingchun |
author_sort | Zhang, Yuanya |
collection | PubMed |
description | The mitogen-activated protein kinase ERK1/2 (ERKs, extracellular-regulated protein kinases) plays important roles in a wide spectrum of cellular processes and have been implicated in many disease states. The spatiotemporal regulation of ERK activity has been extensively studied. However, scarce information has been available regarding the quality control of the kinases to scavenge malfunctioning ERKs. Using site-specific mutagenesis and mass spectrometry, we found that the disruption of the conserved H-bond between Y210 and E237 of ERK1 through point mutation at or naturally occurring nitration on Y210 initiates a quality control program dependent on chaperon systems and CHIP (C-terminal of Hsp70-interacting protein)-mediated ubiquitination and degradation. The H-bond is also important for the quality control of ERK2, but through a distinct mechanism. These findings clearly demonstrate how malfunctioning ERKs are eliminated when cells are in certain stress conditions or unhealthy states, and could represent a general mechanism for scavenging malfunctioning kinases in stress conditions. |
format | Online Article Text |
id | pubmed-6604951 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66049512019-07-10 Nitration-induced ubiquitination and degradation control quality of ERK1 Zhang, Yuanya Huang, Xiahe Wang, Jinlong Wang, Xiaorong Liu, Xiaofei Chen, Yuhang Xu, Wu Wang, Yingchun Biochem J Research Articles The mitogen-activated protein kinase ERK1/2 (ERKs, extracellular-regulated protein kinases) plays important roles in a wide spectrum of cellular processes and have been implicated in many disease states. The spatiotemporal regulation of ERK activity has been extensively studied. However, scarce information has been available regarding the quality control of the kinases to scavenge malfunctioning ERKs. Using site-specific mutagenesis and mass spectrometry, we found that the disruption of the conserved H-bond between Y210 and E237 of ERK1 through point mutation at or naturally occurring nitration on Y210 initiates a quality control program dependent on chaperon systems and CHIP (C-terminal of Hsp70-interacting protein)-mediated ubiquitination and degradation. The H-bond is also important for the quality control of ERK2, but through a distinct mechanism. These findings clearly demonstrate how malfunctioning ERKs are eliminated when cells are in certain stress conditions or unhealthy states, and could represent a general mechanism for scavenging malfunctioning kinases in stress conditions. Portland Press Ltd. 2019-07-15 2019-07-02 /pmc/articles/PMC6604951/ /pubmed/31196894 http://dx.doi.org/10.1042/BCJ20190240 Text en © 2019 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Articles Zhang, Yuanya Huang, Xiahe Wang, Jinlong Wang, Xiaorong Liu, Xiaofei Chen, Yuhang Xu, Wu Wang, Yingchun Nitration-induced ubiquitination and degradation control quality of ERK1 |
title | Nitration-induced ubiquitination and degradation control quality of ERK1 |
title_full | Nitration-induced ubiquitination and degradation control quality of ERK1 |
title_fullStr | Nitration-induced ubiquitination and degradation control quality of ERK1 |
title_full_unstemmed | Nitration-induced ubiquitination and degradation control quality of ERK1 |
title_short | Nitration-induced ubiquitination and degradation control quality of ERK1 |
title_sort | nitration-induced ubiquitination and degradation control quality of erk1 |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604951/ https://www.ncbi.nlm.nih.gov/pubmed/31196894 http://dx.doi.org/10.1042/BCJ20190240 |
work_keys_str_mv | AT zhangyuanya nitrationinducedubiquitinationanddegradationcontrolqualityoferk1 AT huangxiahe nitrationinducedubiquitinationanddegradationcontrolqualityoferk1 AT wangjinlong nitrationinducedubiquitinationanddegradationcontrolqualityoferk1 AT wangxiaorong nitrationinducedubiquitinationanddegradationcontrolqualityoferk1 AT liuxiaofei nitrationinducedubiquitinationanddegradationcontrolqualityoferk1 AT chenyuhang nitrationinducedubiquitinationanddegradationcontrolqualityoferk1 AT xuwu nitrationinducedubiquitinationanddegradationcontrolqualityoferk1 AT wangyingchun nitrationinducedubiquitinationanddegradationcontrolqualityoferk1 |