國家衛生研究院 NHRI:Item 3990099045/15815
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    NHRI > Immunology Research Center > Tse-Hua Tan > Periodical Articles >  Item 3990099045/15815


    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/15815


    Title: UHRF1P contributes to IL-17A-mediated systemic lupus erythematosus via UHRF1-MAP4K3 axis
    Authors: Chuang, HC;Lan, KY;Hsu, PM;Chen, MH;Chen, YM;Yen, JH;Liao, BY;Tan, TH
    Contributors: Immunology Research Center;Institute of Population Health Sciences
    Abstract: Inflammatory T cells contribute to the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Analysis of the T-cell transcriptomics data of two independent SLE patient cohorts by three machine learning models revealed the pseudogene UHRF1P as a novel SLE biomarker. The pseudogene-encoded UHRF1P protein was overexpressed in peripheral blood T cells of SLE patients. The UHRF1P protein lacks the amino-terminus of its parental UHRF1 protein, resulting in missing the proteasome-binding ubiquitin-like (Ubl) domain of UHRF1. T-cell-specific UHRF1P transgenic mice manifested the induction of IL-17A and autoimmune inflammation. Mechanistically, UHFR1P prevented UHRF1-induced Lys48-linked ubiquitination and degradation of MAP4K3 (GLK), which is a kinase known to induce IL-17A. Consistently, IL-17A induction and autoimmune phenotypes of UHRF1P transgenic mice were obliterated by MAP4K3 knockout. Collectively, UHRF1P overexpression in T cells inhibits the E3 ligase function of its parental UHRF1 and induces autoimmune diseases.
    Date: 2024-06
    Relation: Journal of Autoimmunity. 2024 Jun;146:Article number 103221.
    Link to: http://dx.doi.org/10.1016/j.jaut.2024.103221
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0896-8411&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:001232721000001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85190743512
    Appears in Collections:[Tse-Hua Tan] Periodical Articles
    [Huai-Chia Chuang] Periodical Articles
    [Ben-Yang Liao] Periodical Articles

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