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Ugene, a Newly Identified Protein That Is Commonly Overexpressed in Cancer and Binds Uracil DNA Glycosylase

Departments of ¹ Molecular Biology and Microbiology, ² Medicine, and ³ Genetics; ⁴ Case Comprehensive Cancer Center, Case Western Reserve University; ⁵ Case Medical Center; ⁶ Howard Hughes Medical Institute, Cleveland, Ohio; ⁷ PDL BioPHARMA, Redwood City, California; and ⁸ Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas

Requests for reprints: Sanford D. Markowitz, Howard Hughes Medical Institute Laboratory, Wolstein Research Building, 3rd Floor, Mailstop 7285, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-7285. Phone: 216-368-1976; Fax: 216-368-8928; E-mail: sxm10{at}cwru.edu.

Key Words: Ugene • colon cancer • UNG2 • base excision repair

Expression microarrays identified a novel transcript, designated as Ugene, whose expression is absent in normal colon and colon adenomas, but that is commonly induced in malignant colon cancers. These findings were validated by real-time PCR and Northern blot analysis in an independent panel of colon cancer cases. In addition, Ugene expression was found to be elevated in many other common cancer types, including breast, lung, uterus, and ovary. Immunofluorescence of V5-tagged Ugene revealed it to have a nuclear localization. In a pull-down assay, uracil DNA glycosylase 2 (UNG2), an important enzyme in the base excision repair (BER) pathway, was identified as a partner protein that binds to Ugene. Coimmunoprecipitation and Western blot analysis confirmed the binding between the endogenous Ugene and UNG2 proteins. Using deletion constructs, we find that Ugene binds to the first 25 amino acids of the UNG2 NH₂ terminus. We suggest that Ugene induction in cancer may contribute to the cancer phenotype by interacting with the BER pathway. [Cancer Res 2008;68(15):6118–26]