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SUMOs Mediate the Nuclear Transfer of p38 and p-p38 during Helicobacter Pylori Infection

The p38 mitogen activated protein kinase (MAPK) signaling pathway has been suggested to play a significant role in the gastric mucosal inflammatory response to chronic Helicobacter pylori (H. pylori) infection. Nuclear translocation is thought to be important for p38 function, but no nuclear translo...

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Autores principales: Wang, Pin Yao, Hsu, Ping I., Wu, Deng Chyang, Chen, Te Chung, Jarman, Andrew Paul, Powell, Lynn Marie, Chen, Angela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163533/
https://www.ncbi.nlm.nih.gov/pubmed/30135361
http://dx.doi.org/10.3390/ijms19092482
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author Wang, Pin Yao
Hsu, Ping I.
Wu, Deng Chyang
Chen, Te Chung
Jarman, Andrew Paul
Powell, Lynn Marie
Chen, Angela
author_facet Wang, Pin Yao
Hsu, Ping I.
Wu, Deng Chyang
Chen, Te Chung
Jarman, Andrew Paul
Powell, Lynn Marie
Chen, Angela
author_sort Wang, Pin Yao
collection PubMed
description The p38 mitogen activated protein kinase (MAPK) signaling pathway has been suggested to play a significant role in the gastric mucosal inflammatory response to chronic Helicobacter pylori (H. pylori) infection. Nuclear translocation is thought to be important for p38 function, but no nuclear translocation signals have been found in the protein and no nuclear carrier proteins have been identified for p38. We have investigated the role of small ubiquitin-related modifier (SUMO) in the nuclear transfer of p38 in response to H. pylori infection. Exposure of human AGS cells to H. pylori induced the activation of p38 and the expression of SUMOs, especially SUMO-2. SUMO knockdown counteracted the effect of H. pylori infection by decreasing the resulting p38 mediated cellular apoptosis through a reduction in the nuclear fraction of phosphorylated p38. We identified a non-covalent interaction between SUMOs and p38 via SUMO interaction motifs (SIMs), and showed that SUMO-dependent nuclear transfer of p38 was decreased upon mutation of its SIMs. This study has identified a new pathway of p38 nuclear translocation, in response to H. pylori infection. We conclude that in the presence of H. pylori SUMO-2 has a major role in regulating nuclear levels of p38, through non-covalent SUMO-p38 interactions, independent of the p38 phosphorylation state.
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spelling pubmed-61635332018-10-10 SUMOs Mediate the Nuclear Transfer of p38 and p-p38 during Helicobacter Pylori Infection Wang, Pin Yao Hsu, Ping I. Wu, Deng Chyang Chen, Te Chung Jarman, Andrew Paul Powell, Lynn Marie Chen, Angela Int J Mol Sci Article The p38 mitogen activated protein kinase (MAPK) signaling pathway has been suggested to play a significant role in the gastric mucosal inflammatory response to chronic Helicobacter pylori (H. pylori) infection. Nuclear translocation is thought to be important for p38 function, but no nuclear translocation signals have been found in the protein and no nuclear carrier proteins have been identified for p38. We have investigated the role of small ubiquitin-related modifier (SUMO) in the nuclear transfer of p38 in response to H. pylori infection. Exposure of human AGS cells to H. pylori induced the activation of p38 and the expression of SUMOs, especially SUMO-2. SUMO knockdown counteracted the effect of H. pylori infection by decreasing the resulting p38 mediated cellular apoptosis through a reduction in the nuclear fraction of phosphorylated p38. We identified a non-covalent interaction between SUMOs and p38 via SUMO interaction motifs (SIMs), and showed that SUMO-dependent nuclear transfer of p38 was decreased upon mutation of its SIMs. This study has identified a new pathway of p38 nuclear translocation, in response to H. pylori infection. We conclude that in the presence of H. pylori SUMO-2 has a major role in regulating nuclear levels of p38, through non-covalent SUMO-p38 interactions, independent of the p38 phosphorylation state. MDPI 2018-08-22 /pmc/articles/PMC6163533/ /pubmed/30135361 http://dx.doi.org/10.3390/ijms19092482 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Pin Yao
Hsu, Ping I.
Wu, Deng Chyang
Chen, Te Chung
Jarman, Andrew Paul
Powell, Lynn Marie
Chen, Angela
SUMOs Mediate the Nuclear Transfer of p38 and p-p38 during Helicobacter Pylori Infection
title SUMOs Mediate the Nuclear Transfer of p38 and p-p38 during Helicobacter Pylori Infection
title_full SUMOs Mediate the Nuclear Transfer of p38 and p-p38 during Helicobacter Pylori Infection
title_fullStr SUMOs Mediate the Nuclear Transfer of p38 and p-p38 during Helicobacter Pylori Infection
title_full_unstemmed SUMOs Mediate the Nuclear Transfer of p38 and p-p38 during Helicobacter Pylori Infection
title_short SUMOs Mediate the Nuclear Transfer of p38 and p-p38 during Helicobacter Pylori Infection
title_sort sumos mediate the nuclear transfer of p38 and p-p38 during helicobacter pylori infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163533/
https://www.ncbi.nlm.nih.gov/pubmed/30135361
http://dx.doi.org/10.3390/ijms19092482
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