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Intermolecular steric inhibition of Ephexin4 is relieved by Elmo1
Ephexin4, a guanine nucleotide-exchange factor for RhoG, promotes engulfment of apoptotic cells and cancer cell migration in a RhoG-dependent manner, which is synergistically augmented by Elmo1, an Ephexin4-interacting protein. However, the underlying molecular mechanism remains elusive. Here, we re...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493634/ https://www.ncbi.nlm.nih.gov/pubmed/28667327 http://dx.doi.org/10.1038/s41598-017-04810-6 |
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author | Kim, Kwanhyeong Lee, Juyeon Lee, Sang-Ah Moon, Hyunji Park, Boyeon Kim, Deokhwan Joo, Young-Eun Park, Daeho |
author_facet | Kim, Kwanhyeong Lee, Juyeon Lee, Sang-Ah Moon, Hyunji Park, Boyeon Kim, Deokhwan Joo, Young-Eun Park, Daeho |
author_sort | Kim, Kwanhyeong |
collection | PubMed |
description | Ephexin4, a guanine nucleotide-exchange factor for RhoG, promotes engulfment of apoptotic cells and cancer cell migration in a RhoG-dependent manner, which is synergistically augmented by Elmo1, an Ephexin4-interacting protein. However, the underlying molecular mechanism remains elusive. Here, we report a mechanism by which Elmo1 cooperates with Ephexin4 to activate RhoG. We found that Ephexin4 activity was increased by elimination of its SH3 domain which intermolecularly interacts with the N20 region of Ephexin4. This interaction prevented RhoG from binding to Ephexin4 and thus inhibited RhoG activation. Moreover, we also found that Elmo1 associated with the SH3 domain as well as the N20 region and competed with the SH3 domain for binding to the N20 region, interrupting the interaction of the SH3 domain with the N20 region and thereby promoting RhoG binding to Ephexin4. In addition, the activity of Ephexin4 lacking the SH3 domain was comparable to that of Ephexin4 with Elmo1. Taken together, the data suggest that Elmo1 relieves the steric hindrance of Ephexin4 generated by the intermolecular interaction of the SH3 domain and makes Ephexin4 more accessible to RhoG. |
format | Online Article Text |
id | pubmed-5493634 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-54936342017-07-05 Intermolecular steric inhibition of Ephexin4 is relieved by Elmo1 Kim, Kwanhyeong Lee, Juyeon Lee, Sang-Ah Moon, Hyunji Park, Boyeon Kim, Deokhwan Joo, Young-Eun Park, Daeho Sci Rep Article Ephexin4, a guanine nucleotide-exchange factor for RhoG, promotes engulfment of apoptotic cells and cancer cell migration in a RhoG-dependent manner, which is synergistically augmented by Elmo1, an Ephexin4-interacting protein. However, the underlying molecular mechanism remains elusive. Here, we report a mechanism by which Elmo1 cooperates with Ephexin4 to activate RhoG. We found that Ephexin4 activity was increased by elimination of its SH3 domain which intermolecularly interacts with the N20 region of Ephexin4. This interaction prevented RhoG from binding to Ephexin4 and thus inhibited RhoG activation. Moreover, we also found that Elmo1 associated with the SH3 domain as well as the N20 region and competed with the SH3 domain for binding to the N20 region, interrupting the interaction of the SH3 domain with the N20 region and thereby promoting RhoG binding to Ephexin4. In addition, the activity of Ephexin4 lacking the SH3 domain was comparable to that of Ephexin4 with Elmo1. Taken together, the data suggest that Elmo1 relieves the steric hindrance of Ephexin4 generated by the intermolecular interaction of the SH3 domain and makes Ephexin4 more accessible to RhoG. Nature Publishing Group UK 2017-06-30 /pmc/articles/PMC5493634/ /pubmed/28667327 http://dx.doi.org/10.1038/s41598-017-04810-6 Text en © The Author(s) 2017 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 Kim, Kwanhyeong Lee, Juyeon Lee, Sang-Ah Moon, Hyunji Park, Boyeon Kim, Deokhwan Joo, Young-Eun Park, Daeho Intermolecular steric inhibition of Ephexin4 is relieved by Elmo1 |
title | Intermolecular steric inhibition of Ephexin4 is relieved by Elmo1 |
title_full | Intermolecular steric inhibition of Ephexin4 is relieved by Elmo1 |
title_fullStr | Intermolecular steric inhibition of Ephexin4 is relieved by Elmo1 |
title_full_unstemmed | Intermolecular steric inhibition of Ephexin4 is relieved by Elmo1 |
title_short | Intermolecular steric inhibition of Ephexin4 is relieved by Elmo1 |
title_sort | intermolecular steric inhibition of ephexin4 is relieved by elmo1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493634/ https://www.ncbi.nlm.nih.gov/pubmed/28667327 http://dx.doi.org/10.1038/s41598-017-04810-6 |
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