Ubiquitinating enzymes (UBEs) catalyze protein ubiquitination, a reversible process countered by deubiquitinating enzyme (DUB) action. Five DUB subfamilies are recognized, including the USP, UCH, OTU, MJD, and JAMM enzymes. USP4 was originally identified during a survey of murine genes near the Mpv20 retroviral insertion site and initially referred to as Ubiquitous Nuclear Protein (UNP). Analysis of the mouse cDNA originally
identified Usp4/Unp as a proto-oncogene related to the human tre-2/tre-17/USP6 proto-oncogene. Usp4/Unp was subsequently observed to contain the conserved Cys and His boxes of the UBP family as well as DUB activity. In a study of primary lung tumor tissue, it was observed that the human homolog of Usp4, USP4/UNPH, had elevated gene expression levels in small cell tumors and adenocarcinomas of the lung, suggesting a causative role for USP4 in neoplasia. Another recent study demonstrated overexpression of USP4 in several types of human cancer and that USP4 positively contributes to cell transformation by negatively regulating p53 levels. Both murine and human USP4 have been shown to interact with the Rb family of tumor suppressor proteins, providing additional mechanistic evidence of a role for USP4 in cellular transformation.
identified Usp4/Unp as a proto-oncogene related to the human tre-2/tre-17/USP6 proto-oncogene. Usp4/Unp was subsequently observed to contain the conserved Cys and His boxes of the UBP family as well as DUB activity. In a study of primary lung tumor tissue, it was observed that the human homolog of Usp4, USP4/UNPH, had elevated gene expression levels in small cell tumors and adenocarcinomas of the lung, suggesting a causative role for USP4 in neoplasia. Another recent study demonstrated overexpression of USP4 in several types of human cancer and that USP4 positively contributes to cell transformation by negatively regulating p53 levels. Both murine and human USP4 have been shown to interact with the Rb family of tumor suppressor proteins, providing additional mechanistic evidence of a role for USP4 in cellular transformation.