國家衛生研究院 NHRI:Item 3990099045/6887
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    题名: Caveolin-1 facilitates cyclooxygenase-2 degradation through a p97/valosin-containing protein dependent pathway
    作者: Shyue, SK;Chen, SF;Liou, JY;Wu, KK
    贡献者: Institute of Cellular and Systems Medicine
    摘要: Cyclooxygenase (COX)-2 participates in various physiological functions and involves in tumorigenesis. Although transactivation of COX-2 has been well studied, the factor that responsible for COX-2 degradation remains mostly unknown. In this study, COX-2 degradation induced by caveolin-1 (Cav-1) is demonstrated by upregulated endogenous and bacteria induced COX-2 in lung and colon of caveolin-1 null mice. Ectopic expression of caveolin-1 in HT-29 cells resulted in suppressed endogenous and IL-1β induced COX-2 expression. Cav-1-induced COX-2 degradation was implicated to enhanced protein degradation by the ubiquitin-proteosome pathway. Via immunoprecipitation, we identified valosin-containing protein (VCP/p97) as the chaperon protein which interacts with both Cav-1 and COX-2 and specifically mediates COX-2, but not COX-1, degradation. Suppression of VCP via siRNA resulted in increased COX-2 level with prolonged half-life. Moreover, deletion of the COX-2 C-terminal 32 amino acids upregulated its expression level and lengthened its half-life. These data reveal a novel degradation mechanism that Cav-1 and VCP synergistically orchestrate COX-2 degradation, suggesting a role of Cav-1 in anti-tumorigenesis.
    日期: 2008-04
    關聯: FASEB Journal. 2008 Apr;22(Suppl.):998.5.
    Link to: http://www.fasebj.org/cgi/content/meeting_abstract/22/1_MeetingAbstracts/998.5
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0892-6638&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000208467802700
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