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The E3 ubiquitin ligase RNF185 facilitates the cGAS-mediated innate immune response
The cyclic GMP-AMP synthase (cGAS), upon cytosolic DNA stimulation, catalyzes the formation of the second messenger 2′3′-cGAMP, which then binds to stimulator of interferon genes (STING) and activates downstream signaling. It remains to be elucidated how the cGAS enzymatic activity is modulated dyna...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5358892/ https://www.ncbi.nlm.nih.gov/pubmed/28273161 http://dx.doi.org/10.1371/journal.ppat.1006264 |
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author | Wang, Qiang Huang, Liyuan Hong, Ze Lv, Zhongshi Mao, Zhaomin Tang, Yijun Kong, Xiufang Li, Senlin Cui, Ye Liu, Heng Zhang, Lele Zhang, Xiaojie Jiang, Lindi Wang, Chen Zhou, Qin |
author_facet | Wang, Qiang Huang, Liyuan Hong, Ze Lv, Zhongshi Mao, Zhaomin Tang, Yijun Kong, Xiufang Li, Senlin Cui, Ye Liu, Heng Zhang, Lele Zhang, Xiaojie Jiang, Lindi Wang, Chen Zhou, Qin |
author_sort | Wang, Qiang |
collection | PubMed |
description | The cyclic GMP-AMP synthase (cGAS), upon cytosolic DNA stimulation, catalyzes the formation of the second messenger 2′3′-cGAMP, which then binds to stimulator of interferon genes (STING) and activates downstream signaling. It remains to be elucidated how the cGAS enzymatic activity is modulated dynamically. Here, we reported that the ER ubiquitin ligase RNF185 interacted with cGAS during HSV-1 infection. Ectopic-expression or knockdown of RNF185 respectively enhanced or impaired the IRF3-responsive gene expression. Mechanistically, RNF185 specifically catalyzed the K27-linked poly-ubiquitination of cGAS, which promoted its enzymatic activity. Additionally, Systemic Lupus Erythematosus (SLE) patients displayed elevated expression of RNF185 mRNA. Collectively, this study uncovers RNF185 as the first E3 ubiquitin ligase of cGAS, shedding light on the regulation of cGAS activity in innate immune responses. |
format | Online Article Text |
id | pubmed-5358892 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-53588922017-04-06 The E3 ubiquitin ligase RNF185 facilitates the cGAS-mediated innate immune response Wang, Qiang Huang, Liyuan Hong, Ze Lv, Zhongshi Mao, Zhaomin Tang, Yijun Kong, Xiufang Li, Senlin Cui, Ye Liu, Heng Zhang, Lele Zhang, Xiaojie Jiang, Lindi Wang, Chen Zhou, Qin PLoS Pathog Research Article The cyclic GMP-AMP synthase (cGAS), upon cytosolic DNA stimulation, catalyzes the formation of the second messenger 2′3′-cGAMP, which then binds to stimulator of interferon genes (STING) and activates downstream signaling. It remains to be elucidated how the cGAS enzymatic activity is modulated dynamically. Here, we reported that the ER ubiquitin ligase RNF185 interacted with cGAS during HSV-1 infection. Ectopic-expression or knockdown of RNF185 respectively enhanced or impaired the IRF3-responsive gene expression. Mechanistically, RNF185 specifically catalyzed the K27-linked poly-ubiquitination of cGAS, which promoted its enzymatic activity. Additionally, Systemic Lupus Erythematosus (SLE) patients displayed elevated expression of RNF185 mRNA. Collectively, this study uncovers RNF185 as the first E3 ubiquitin ligase of cGAS, shedding light on the regulation of cGAS activity in innate immune responses. Public Library of Science 2017-03-08 /pmc/articles/PMC5358892/ /pubmed/28273161 http://dx.doi.org/10.1371/journal.ppat.1006264 Text en © 2017 Wang 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Wang, Qiang Huang, Liyuan Hong, Ze Lv, Zhongshi Mao, Zhaomin Tang, Yijun Kong, Xiufang Li, Senlin Cui, Ye Liu, Heng Zhang, Lele Zhang, Xiaojie Jiang, Lindi Wang, Chen Zhou, Qin The E3 ubiquitin ligase RNF185 facilitates the cGAS-mediated innate immune response |
title | The E3 ubiquitin ligase RNF185 facilitates the cGAS-mediated innate immune response |
title_full | The E3 ubiquitin ligase RNF185 facilitates the cGAS-mediated innate immune response |
title_fullStr | The E3 ubiquitin ligase RNF185 facilitates the cGAS-mediated innate immune response |
title_full_unstemmed | The E3 ubiquitin ligase RNF185 facilitates the cGAS-mediated innate immune response |
title_short | The E3 ubiquitin ligase RNF185 facilitates the cGAS-mediated innate immune response |
title_sort | e3 ubiquitin ligase rnf185 facilitates the cgas-mediated innate immune response |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5358892/ https://www.ncbi.nlm.nih.gov/pubmed/28273161 http://dx.doi.org/10.1371/journal.ppat.1006264 |
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