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Pc2‐mediated SUMOylation of WWOX is essential for its suppression of DU145 prostate tumorigenesis
Author(s) -
Choi Hye-Jin,
Park Jung-Hwan,
Park Jong-Hwan,
Lee Kyung Bok,
Oh Sang-Muk
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.11.028
Subject(s) - wwox , du145 , sumo protein , carcinogenesis , cancer research , prostate cancer , ectopic expression , chemistry , cancer cell , suppressor , microbiology and biotechnology , biology , cancer , ubiquitin , biochemistry , gene , genetics , lncap
Tumor suppressor WW domain‐containing oxidoreductase (WWOX) is depleted in various cancer types. Here we report that WWOX is modified by small ubiquitin‐like modifier (SUMO) proteins and represses DU145 prostate cancer tumorigenesis in a SUMOylation‐dependent manner. Ectopic WWOX was shown to associate with SUMO2/3 or E2 Ubc9. Furthermore, we revealed that WWOX SUMOylation was promoted by E3 ligase polycomb2 (Pc2), and that WWOX associated with Pc2. Meanwhile, anisomycin‐induced activator protein‐1 (AP‐1) activity was markedly diminished by co‐expression of SUMO and WWOX. Also, WWOX wild type (WT), but not WWOX SUMO mutant (K176A) markedly reduced both DU145 prostate cancer cell proliferation and xenograft tumorigenesis. Collectively, our findings demonstrate that SUMO modification of WWOX is essential for its suppressive activity for DU145 prostate cancer tumorigenesis.