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Regulation of autophagy by E3 ubiquitin ligase RNF216 through BECN1 ubiquitination

Autophagy is an evolutionarily conserved biological process involved in an array of physiological and pathological events. Without proper control, autophagy contributes to various disorders, including cancer and autoimmune and inflammatory diseases. It is therefore of vital importance that autophagy...

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Autores principales: Xu, Congfeng, Feng, Kuan, Zhao, Xiaonan, Huang, Shiqian, Cheng, Yiji, Qian, Liu, Wang, Yanan, Sun, Hongxing, Jin, Min, Chuang, Tsung-Hsien, Zhang, Yanyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4502788/
https://www.ncbi.nlm.nih.gov/pubmed/25484083
http://dx.doi.org/10.4161/15548627.2014.981792
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author Xu, Congfeng
Feng, Kuan
Zhao, Xiaonan
Huang, Shiqian
Cheng, Yiji
Qian, Liu
Wang, Yanan
Sun, Hongxing
Jin, Min
Chuang, Tsung-Hsien
Zhang, Yanyun
author_facet Xu, Congfeng
Feng, Kuan
Zhao, Xiaonan
Huang, Shiqian
Cheng, Yiji
Qian, Liu
Wang, Yanan
Sun, Hongxing
Jin, Min
Chuang, Tsung-Hsien
Zhang, Yanyun
author_sort Xu, Congfeng
collection PubMed
description Autophagy is an evolutionarily conserved biological process involved in an array of physiological and pathological events. Without proper control, autophagy contributes to various disorders, including cancer and autoimmune and inflammatory diseases. It is therefore of vital importance that autophagy is under careful balance. Thus, additional regulators undoubtedly deepen our understanding of the working network, and provide potential therapeutic targets for disorders. In this study, we found that RNF216 (ring finger protein 216), an E3 ubiquitin ligase, strongly inhibits autophagy in macrophages. Further exploration demonstrates that RNF216 interacts with BECN1, a key regulator in autophagy, and leads to ubiquitination of BECN1, thereby contributing to BECN1 degradation. RNF216 was involved in the ubiquitination of lysine 48 of BECN1 through direct interaction with the triad (2 RING fingers and a DRIL [double RING finger linked]) domain. We further showed that inhibition of autophagy through overexpression of RNF216 in alveolar macrophages promotes Listeria monocytogenes growth and distribution, while knockdown of RNF216 significantly inhibited these outcomes. These effects were confirmed in a mouse model of L. monocytogenes infection, suggesting that manipulating RNF216 expression could be a therapeutic approach. Thus, our study identifies a novel negative regulator of autophagy and suggests that RNF216 may be a target for treatment of inflammatory diseases.
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spelling pubmed-45027882016-01-28 Regulation of autophagy by E3 ubiquitin ligase RNF216 through BECN1 ubiquitination Xu, Congfeng Feng, Kuan Zhao, Xiaonan Huang, Shiqian Cheng, Yiji Qian, Liu Wang, Yanan Sun, Hongxing Jin, Min Chuang, Tsung-Hsien Zhang, Yanyun Autophagy Basic Research Papers Autophagy is an evolutionarily conserved biological process involved in an array of physiological and pathological events. Without proper control, autophagy contributes to various disorders, including cancer and autoimmune and inflammatory diseases. It is therefore of vital importance that autophagy is under careful balance. Thus, additional regulators undoubtedly deepen our understanding of the working network, and provide potential therapeutic targets for disorders. In this study, we found that RNF216 (ring finger protein 216), an E3 ubiquitin ligase, strongly inhibits autophagy in macrophages. Further exploration demonstrates that RNF216 interacts with BECN1, a key regulator in autophagy, and leads to ubiquitination of BECN1, thereby contributing to BECN1 degradation. RNF216 was involved in the ubiquitination of lysine 48 of BECN1 through direct interaction with the triad (2 RING fingers and a DRIL [double RING finger linked]) domain. We further showed that inhibition of autophagy through overexpression of RNF216 in alveolar macrophages promotes Listeria monocytogenes growth and distribution, while knockdown of RNF216 significantly inhibited these outcomes. These effects were confirmed in a mouse model of L. monocytogenes infection, suggesting that manipulating RNF216 expression could be a therapeutic approach. Thus, our study identifies a novel negative regulator of autophagy and suggests that RNF216 may be a target for treatment of inflammatory diseases. Taylor & Francis 2015-01-28 /pmc/articles/PMC4502788/ /pubmed/25484083 http://dx.doi.org/10.4161/15548627.2014.981792 Text en © 2014 The Author(s). Published with license by Taylor & Francis http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
spellingShingle Basic Research Papers
Xu, Congfeng
Feng, Kuan
Zhao, Xiaonan
Huang, Shiqian
Cheng, Yiji
Qian, Liu
Wang, Yanan
Sun, Hongxing
Jin, Min
Chuang, Tsung-Hsien
Zhang, Yanyun
Regulation of autophagy by E3 ubiquitin ligase RNF216 through BECN1 ubiquitination
title Regulation of autophagy by E3 ubiquitin ligase RNF216 through BECN1 ubiquitination
title_full Regulation of autophagy by E3 ubiquitin ligase RNF216 through BECN1 ubiquitination
title_fullStr Regulation of autophagy by E3 ubiquitin ligase RNF216 through BECN1 ubiquitination
title_full_unstemmed Regulation of autophagy by E3 ubiquitin ligase RNF216 through BECN1 ubiquitination
title_short Regulation of autophagy by E3 ubiquitin ligase RNF216 through BECN1 ubiquitination
title_sort regulation of autophagy by e3 ubiquitin ligase rnf216 through becn1 ubiquitination
topic Basic Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4502788/
https://www.ncbi.nlm.nih.gov/pubmed/25484083
http://dx.doi.org/10.4161/15548627.2014.981792
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