國家衛生研究院 NHRI:Item 3990099045/14331
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/14331


    Title: DUSP3 regulates phosphorylation-mediated degradation of occludin and is required for maintaining epithelial tight junction
    Authors: Chou, HC;Cheng, CM;Yang, CH;Lin, TY;Liu, YW;Tan, TH;Chen, YR
    Contributors: Institute of Molecular and Genomic Medicine;Immunology Research Center
    Abstract: Background Tight junctions (TJ) are multi-protein complexes that hold epithelial cells together and form structural and functional barriers for maintaining proper biological activities. Dual specificity phosphatase 3 (DUSP3), a suppressor of multiple protein tyrosine (Tyr) kinases, is decreased in lung cancer tissues. Here we demonstrated the role of DUSP3 in regulation of epithelial TJ. Methods Barrier functions of TJ were examined in wild-type or DUSP3-deficient lung epithelial cells. Animal and clinical data were analyzed for the association between DUSP3 deficiency and lung cancer progression. Proximity ligation assay, immunoblotting, and phosphatase assay were performed to study the effect of DUSP3 on the TJ protein occludin (OCLN). Mutations of Tyr residues on OCLN showed the role of Tyr phosphorylation in regulating OCLN. Results Compared to those of the DUSP3-expressing cells, we found the expression and distribution of ZO-1, a TJ-anchoring molecule, were abnormal in DUSP3-deficient cells. OCLN had an increased phosphorylation level in DUSP3-deficient cells. We identified that OCLN is a direct substrate of DUSP3. DUSP3 regulated OCLN ubiquitination and degradation through decreasing OCLN tyrosine phosphorylation directly or through suppressing focal adhesion kinase, the OCLN kinase. Conclusion Our study revealed that DUSP3 is an important TJ regulatory protein and its decrease may be involved in progression of epithelial cancers.
    Date: 2022-06-15
    Relation: Journal of Biomedical Science. 2022 Jun 15;29:Article number 40.
    Link to: http://dx.doi.org/10.1186/s12929-022-00826-x
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1021-7770&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000811759600001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85131930726
    Appears in Collections:[Yi-Rong Chen] Periodical Articles
    [Tse-Hua Tan] Periodical Articles

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