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Extracellular signal-regulated kinases associate with and phosphorylate DHPS to promote cell proliferation
The ERK1/2 pathway is one of the most commonly dysregulated pathways in human cancers and controls many vital cellular processes. Although many ERK1/2 kinase substrates have been identified, the diversity of ERK1/2 mediated processes suggests the existence of additional targets. Here, we identified...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522278/ https://www.ncbi.nlm.nih.gov/pubmed/32989218 http://dx.doi.org/10.1038/s41389-020-00271-1 |
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author | Wang, Chao Chen, Zhen Nie, Litong Tang, Mengfan Feng, Xu Su, Dan Zhang, Huimin Xiong, Yun Park, Jeong-Min Chen, Junjie |
author_facet | Wang, Chao Chen, Zhen Nie, Litong Tang, Mengfan Feng, Xu Su, Dan Zhang, Huimin Xiong, Yun Park, Jeong-Min Chen, Junjie |
author_sort | Wang, Chao |
collection | PubMed |
description | The ERK1/2 pathway is one of the most commonly dysregulated pathways in human cancers and controls many vital cellular processes. Although many ERK1/2 kinase substrates have been identified, the diversity of ERK1/2 mediated processes suggests the existence of additional targets. Here, we identified Deoxyhypusine synthase (DHPS), an essential hypusination enzyme regulating protein translation, as a major and direct-binding protein of ERK1/2. Further experiments showed that ERK1/2 phosphorylate DHPS at Ser-233 site. The Ser-233 phosphorylation of DHPS by ERK1/2 is important for its function in cell proliferation. Moreover, we found that higher DHPS expression correlated with poor prognosis in lung adenocarcinoma and increased resistance to inhibitors of the ERK1/2 pathway. In summary, our results suggest that ERK1/2-mediated DHPS phosphorylation is an important mechanism that underlies protein translation and that DHPS expression is a potent biomarker of response to therapies targeting ERK1/2-pathway. |
format | Online Article Text |
id | pubmed-7522278 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75222782020-10-19 Extracellular signal-regulated kinases associate with and phosphorylate DHPS to promote cell proliferation Wang, Chao Chen, Zhen Nie, Litong Tang, Mengfan Feng, Xu Su, Dan Zhang, Huimin Xiong, Yun Park, Jeong-Min Chen, Junjie Oncogenesis Article The ERK1/2 pathway is one of the most commonly dysregulated pathways in human cancers and controls many vital cellular processes. Although many ERK1/2 kinase substrates have been identified, the diversity of ERK1/2 mediated processes suggests the existence of additional targets. Here, we identified Deoxyhypusine synthase (DHPS), an essential hypusination enzyme regulating protein translation, as a major and direct-binding protein of ERK1/2. Further experiments showed that ERK1/2 phosphorylate DHPS at Ser-233 site. The Ser-233 phosphorylation of DHPS by ERK1/2 is important for its function in cell proliferation. Moreover, we found that higher DHPS expression correlated with poor prognosis in lung adenocarcinoma and increased resistance to inhibitors of the ERK1/2 pathway. In summary, our results suggest that ERK1/2-mediated DHPS phosphorylation is an important mechanism that underlies protein translation and that DHPS expression is a potent biomarker of response to therapies targeting ERK1/2-pathway. Nature Publishing Group UK 2020-09-28 /pmc/articles/PMC7522278/ /pubmed/32989218 http://dx.doi.org/10.1038/s41389-020-00271-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Wang, Chao Chen, Zhen Nie, Litong Tang, Mengfan Feng, Xu Su, Dan Zhang, Huimin Xiong, Yun Park, Jeong-Min Chen, Junjie Extracellular signal-regulated kinases associate with and phosphorylate DHPS to promote cell proliferation |
title | Extracellular signal-regulated kinases associate with and phosphorylate DHPS to promote cell proliferation |
title_full | Extracellular signal-regulated kinases associate with and phosphorylate DHPS to promote cell proliferation |
title_fullStr | Extracellular signal-regulated kinases associate with and phosphorylate DHPS to promote cell proliferation |
title_full_unstemmed | Extracellular signal-regulated kinases associate with and phosphorylate DHPS to promote cell proliferation |
title_short | Extracellular signal-regulated kinases associate with and phosphorylate DHPS to promote cell proliferation |
title_sort | extracellular signal-regulated kinases associate with and phosphorylate dhps to promote cell proliferation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522278/ https://www.ncbi.nlm.nih.gov/pubmed/32989218 http://dx.doi.org/10.1038/s41389-020-00271-1 |
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