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Through screening of various deubiquitinating enzymes (DUBs), we identified ubiquitin specific protease 4 (USP4) as a candidate for \u03b2\u2010catenin\u2010specific DUB. The effects of USP4 overexpression or knockdown suggested that USP4 positively controls the stability of \u03b2\u2010catenin and enhances \u03b2\u2010catenin\u2010regulated transcription. Domain mapping results revealed that the C\u2010terminal catalytic domain is responsible for \u03b2\u2010catenin binding and nuclear transport. Examination of colon cancer tissues from patients revealed a correlation between elevated expression levels of USP4 and \u03b2\u2010catenin. Consistent with this correlation, USP4 knockdown in HCT116, a colon cancer cell line, reduced invasion and migration activity. These observations indicate that USP4 acts as a positive regulator of the WNT\/\u03b2\u2010catenin pathway by deubiquitination and facilitates nuclear localization of \u03b2\u2010catenin. 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