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Caveolin‐1 facilitates cyclooxygenase‐2 degradation through a p97/valosin‐containing protein dependent pathway
Author(s) -
Shyue SongKun,
Chen SuFen,
Liou JunYang,
Wu Kenneth K
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.998.5
Subject(s) - downregulation and upregulation , caveolin 1 , transactivation , immunoprecipitation , chemistry , microbiology and biotechnology , protein degradation , ubiquitin , carcinogenesis , proteasome , cyclooxygenase , biology , biochemistry , enzyme , gene expression , gene
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.