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The Ubiquitin Ligase TRAF6 Negatively Regulates the JAK-STAT Signaling Pathway by Binding to STAT3 and Mediating Its Ubiquitination

STAT3 is a key transcription factor that mediates various cellular and organismal processes, such as cell growth, apoptosis, immune response and cancer. However, the molecular mechanisms of STAT3 regulation remain poorly understood. Here, we identified TRAF6 as a new STAT3 interactor. TRAF6 augmente...

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Autores principales: Wei, Juncheng, Yuan, Yanzhi, Jin, Chaozhi, Chen, Hui, Leng, Ling, He, Fuchu, Wang, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501508/
https://www.ncbi.nlm.nih.gov/pubmed/23185365
http://dx.doi.org/10.1371/journal.pone.0049567
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author Wei, Juncheng
Yuan, Yanzhi
Jin, Chaozhi
Chen, Hui
Leng, Ling
He, Fuchu
Wang, Jian
author_facet Wei, Juncheng
Yuan, Yanzhi
Jin, Chaozhi
Chen, Hui
Leng, Ling
He, Fuchu
Wang, Jian
author_sort Wei, Juncheng
collection PubMed
description STAT3 is a key transcription factor that mediates various cellular and organismal processes, such as cell growth, apoptosis, immune response and cancer. However, the molecular mechanisms of STAT3 regulation remain poorly understood. Here, we identified TRAF6 as a new STAT3 interactor. TRAF6 augmented the ubiquitination of STAT3 and deactivated its transcriptional activity induced by IFNα stimulation or overexpressed with JAK2. Both the RING domain and the TRAF-type zinc finger domain of TRAF6 were indispensable for STAT3 deactivation. Accordingly, TRAF6 also down-regulated the expression of two known STAT3 target genes, CRP and ACT. Therefore, we showed that TRAF6 is a new regulator of JAK/STAT signaling and provide a new mechanistic explanation for the crosstalk between the NF-κB and the JAK-STAT pathways.
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spelling pubmed-35015082012-11-26 The Ubiquitin Ligase TRAF6 Negatively Regulates the JAK-STAT Signaling Pathway by Binding to STAT3 and Mediating Its Ubiquitination Wei, Juncheng Yuan, Yanzhi Jin, Chaozhi Chen, Hui Leng, Ling He, Fuchu Wang, Jian PLoS One Research Article STAT3 is a key transcription factor that mediates various cellular and organismal processes, such as cell growth, apoptosis, immune response and cancer. However, the molecular mechanisms of STAT3 regulation remain poorly understood. Here, we identified TRAF6 as a new STAT3 interactor. TRAF6 augmented the ubiquitination of STAT3 and deactivated its transcriptional activity induced by IFNα stimulation or overexpressed with JAK2. Both the RING domain and the TRAF-type zinc finger domain of TRAF6 were indispensable for STAT3 deactivation. Accordingly, TRAF6 also down-regulated the expression of two known STAT3 target genes, CRP and ACT. Therefore, we showed that TRAF6 is a new regulator of JAK/STAT signaling and provide a new mechanistic explanation for the crosstalk between the NF-κB and the JAK-STAT pathways. Public Library of Science 2012-11-19 /pmc/articles/PMC3501508/ /pubmed/23185365 http://dx.doi.org/10.1371/journal.pone.0049567 Text en © 2012 Wei 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
Wei, Juncheng
Yuan, Yanzhi
Jin, Chaozhi
Chen, Hui
Leng, Ling
He, Fuchu
Wang, Jian
The Ubiquitin Ligase TRAF6 Negatively Regulates the JAK-STAT Signaling Pathway by Binding to STAT3 and Mediating Its Ubiquitination
title The Ubiquitin Ligase TRAF6 Negatively Regulates the JAK-STAT Signaling Pathway by Binding to STAT3 and Mediating Its Ubiquitination
title_full The Ubiquitin Ligase TRAF6 Negatively Regulates the JAK-STAT Signaling Pathway by Binding to STAT3 and Mediating Its Ubiquitination
title_fullStr The Ubiquitin Ligase TRAF6 Negatively Regulates the JAK-STAT Signaling Pathway by Binding to STAT3 and Mediating Its Ubiquitination
title_full_unstemmed The Ubiquitin Ligase TRAF6 Negatively Regulates the JAK-STAT Signaling Pathway by Binding to STAT3 and Mediating Its Ubiquitination
title_short The Ubiquitin Ligase TRAF6 Negatively Regulates the JAK-STAT Signaling Pathway by Binding to STAT3 and Mediating Its Ubiquitination
title_sort ubiquitin ligase traf6 negatively regulates the jak-stat signaling pathway by binding to stat3 and mediating its ubiquitination
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501508/
https://www.ncbi.nlm.nih.gov/pubmed/23185365
http://dx.doi.org/10.1371/journal.pone.0049567
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