Cloning and characterization of a novel human ubiquitin-specific protease,a homologue of murine UBP43 (Usp18)

The ubiquitin-specific proteases (UBP) are a family of enzymes that cleave ubiquitin from ubiquitinated protein substrates. We have recently cloned UB P43, a novel member of this family from ARL1-ETO knock-in mice. To analyze the role of UBP43 in hematopoiesis and leukemogenesis, we have cloned a ful l-length human UBP43 cDNA by screening a human monocytic cDNA Library as we ll as by 5'- and 3'-rapid amplification of cDNA ends analyses. This cDNA en codes a poly-peptide of 372 amino acids with all of the structural motifs o f a deubiquitinating enzyme. The human UBP43 mRNA is strongly expressed in human liver and thymus. Transfection analysis has demonstrated that UBP43 i s a nuclear protein. interestingly, the gene encoding human UBP43 maps to c hromosome 22q11.2. This region, known as DiGeorge syndrome critical region, contains a minimal area of 2 Mb and is consistently deleted in DiGeorge sy ndrome and related, disorders. The syndrome is marked by thymic aplasia or hypoplasia, parathyroid hypoplasia, or congenital cardiac abnormalities. Ta ken together, our results broaden the understanding of a nem human uitin-sp ecific protease, UBP43, and suggest that this gene may also be related to D iGeorge syndrome. (C) 2000 Academic Press.