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CYLD Regulates RhoA Activity by Modulating LARG Ubiquitination
Rho family guanosine triphosphatases (GTPases), such as RhoA, Cdc42, and Rac1, play a fundamental role in various cellular processes. The activation of Rho proteins is catalyzed by guanine nucleotide-exchange factors (GEFs), which promote the exchange of GDP for GTP. The precise mechanisms regulatin...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566121/ https://www.ncbi.nlm.nih.gov/pubmed/23405219 http://dx.doi.org/10.1371/journal.pone.0055833 |
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author | Yang, Yunfan Sun, Lei Tala, Gao, Jinmin Li, Dengwen Zhou, Jun Liu, Min |
author_facet | Yang, Yunfan Sun, Lei Tala, Gao, Jinmin Li, Dengwen Zhou, Jun Liu, Min |
author_sort | Yang, Yunfan |
collection | PubMed |
description | Rho family guanosine triphosphatases (GTPases), such as RhoA, Cdc42, and Rac1, play a fundamental role in various cellular processes. The activation of Rho proteins is catalyzed by guanine nucleotide-exchange factors (GEFs), which promote the exchange of GDP for GTP. The precise mechanisms regulating the activation of Rho proteins are not fully understood. Herein, we demonstrate that RhoA activity is regulated by cylindromatosis (CYLD), a deubiquitinase harboring multiple functions. In addition, we find that RhoA-mediated cytoskeletal rearrangement, chromosome separation, and cell polarization are altered in CYLD-depleted cells. Mechanistically, CYLD does not interact with RhoA; instead, it interacts with and deubiquitinates leukemia-associated RhoGEF (LARG). Our data further show that CYLD-mediated deubiquitination of LARG enhances its ability to stimulate the GDP/GTP exchange on RhoA. These data thus identify LARG as a new substrate of CYLD and provide novel insights into the regulation of RhoA activation. Our results also suggest that the LARG-RhoA signaling pathway may play a role in diverse CYLD-mediated cellular events. |
format | Online Article Text |
id | pubmed-3566121 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35661212013-02-12 CYLD Regulates RhoA Activity by Modulating LARG Ubiquitination Yang, Yunfan Sun, Lei Tala, Gao, Jinmin Li, Dengwen Zhou, Jun Liu, Min PLoS One Research Article Rho family guanosine triphosphatases (GTPases), such as RhoA, Cdc42, and Rac1, play a fundamental role in various cellular processes. The activation of Rho proteins is catalyzed by guanine nucleotide-exchange factors (GEFs), which promote the exchange of GDP for GTP. The precise mechanisms regulating the activation of Rho proteins are not fully understood. Herein, we demonstrate that RhoA activity is regulated by cylindromatosis (CYLD), a deubiquitinase harboring multiple functions. In addition, we find that RhoA-mediated cytoskeletal rearrangement, chromosome separation, and cell polarization are altered in CYLD-depleted cells. Mechanistically, CYLD does not interact with RhoA; instead, it interacts with and deubiquitinates leukemia-associated RhoGEF (LARG). Our data further show that CYLD-mediated deubiquitination of LARG enhances its ability to stimulate the GDP/GTP exchange on RhoA. These data thus identify LARG as a new substrate of CYLD and provide novel insights into the regulation of RhoA activation. Our results also suggest that the LARG-RhoA signaling pathway may play a role in diverse CYLD-mediated cellular events. Public Library of Science 2013-02-06 /pmc/articles/PMC3566121/ /pubmed/23405219 http://dx.doi.org/10.1371/journal.pone.0055833 Text en © 2013 Yang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Yang, Yunfan Sun, Lei Tala, Gao, Jinmin Li, Dengwen Zhou, Jun Liu, Min CYLD Regulates RhoA Activity by Modulating LARG Ubiquitination |
title | CYLD Regulates RhoA Activity by Modulating LARG Ubiquitination |
title_full | CYLD Regulates RhoA Activity by Modulating LARG Ubiquitination |
title_fullStr | CYLD Regulates RhoA Activity by Modulating LARG Ubiquitination |
title_full_unstemmed | CYLD Regulates RhoA Activity by Modulating LARG Ubiquitination |
title_short | CYLD Regulates RhoA Activity by Modulating LARG Ubiquitination |
title_sort | cyld regulates rhoa activity by modulating larg ubiquitination |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566121/ https://www.ncbi.nlm.nih.gov/pubmed/23405219 http://dx.doi.org/10.1371/journal.pone.0055833 |
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