國家衛生研究院 NHRI:Item 3990099045/8549
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/8549


    Title: Regulation of autophagy by E3 ubiquitin ligase RNF216 through BECN1 ubiquitination
    Authors: Xu, CF;Feng, K;Zhao, XN;Huang, SQ;Cheng, YJ;Qian, L;Wang, YN;Sun, HX;Jin, M;Chuang, TH;Zhang, YY
    Contributors: Immunology Research Center
    Abstract: 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.
    Date: 2014-12
    Relation: Autophagy. 2014 Dec;10(12):2239-2250.
    Link to: http://dx.doi.org/10.4161/15548627.2014.981792
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1554-8627&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000348598200011
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84922360479
    Appears in Collections:[Tsung-Hsien Chuang] Periodical Articles

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