HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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.
AuthorsHye-Jin Choi, Jung-Hwan Park, Jong-Hwan Park, Kyung Bok Lee, Sang-Muk Oh
JournalFEBS letters (FEBS Lett) Vol. 589 Issue 24 Pt B Pg. 3977-88 (Dec 21 2015) ISSN: 1873-3468 [Electronic] England
PMID26592150 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Chemical References
  • Neoplasm Proteins
  • Recombinant Fusion Proteins
  • Tumor Suppressor Proteins
  • Green Fluorescent Proteins
  • Oxidoreductases
  • WW Domain-Containing Oxidoreductase
  • WWOX protein, human
  • Polycomb Repressive Complex 2
Topics
  • Amino Acid Substitution
  • Animals
  • Carcinogenesis
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Green Fluorescent Proteins (genetics, metabolism)
  • HEK293 Cells
  • Humans
  • Male
  • Mice, Nude
  • Mutation
  • Neoplasm Proteins (genetics, metabolism)
  • Neoplasm Transplantation
  • Oxidoreductases (genetics, metabolism)
  • Polycomb Repressive Complex 2 (metabolism)
  • Prostate (enzymology, metabolism, pathology)
  • Prostatic Neoplasms (enzymology, metabolism, pathology)
  • Random Allocation
  • Recombinant Fusion Proteins (metabolism)
  • Sumoylation
  • Tumor Burden
  • Tumor Suppressor Proteins (genetics, metabolism)
  • WW Domain-Containing Oxidoreductase

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: