We have cloned a novel gene encoding a human ubiquitin-specific protease (USP1). The product, which consists of 785 amino acids with a deduced molecular mass of 88.2 kDa, possesses His and Cys domains that are highly conserved in all members of the ubiquitin-specific processing (UBP) family of proteases. Recombinant USP1 protein showed genuine UBP activity, correctly cleaving Ub-beta-galactosidase to produce ubiquitin and beta-galactosidase. Chromosomal mapping by fluorescence in situ hybridization and radiation hybrid analyses localized the USP1 gene to the p31.3-p32.1 band of chromosome 1. As losses of heterozygosity or amplifications have been observed in the distal region of the short arm of chromosome 1 in some neuroblastomas, breast cancers, and pancreatic adenocarcinomas, the USP1 gene may be a candidate for either the tumor-suppressive or the oncogenic activities associated with that chromosomal region.
Copyright 1998 Academic Press.