title: Pc2-mediated SUMOylation of WWOX is essential for its suppression of DU145 prostate tumorigenesis.
abstract: 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.
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302-832, Republic of Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302-832, Republic of Korea.
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Park
authors.affiliation: Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302-832, Republic of Korea.
authors.forename: Kyung Bok
authors.initials: KB
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302-832, Republic of Korea. Electronic address: sangmuk_oh@konyang.ac.kr.
authors.forename: Sang-Muk
authors.initials: SM
authors.lastname: Oh
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008819:Mice, Nude; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D011467:Prostate / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D058207:Sumoylation; D047368:Tumor Burden; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D000074584:WW Domain-Containing Oxidoreductase
chemical_list: D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; D049452:Green Fluorescent Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human; D063151:Polycomb Repressive Complex 2
keywords: Activator protein-1; Proliferation; Small ubiquitin-like modifier; Tumorigenesis; WW domain-containing oxidoreductase