Scientists have identified a gene (USP9X) that slows the spread of pancreatic cancer tumours, paving the way for targeted treatment of one of the deadliest forms of the disease. After discovering the gene USP9X at work in a study of pancreatic cancer in mice, the international research team found it also played a role in humans. USP9X is a member of the peptidase C19 family and encodes a protein that is similar to ubiquitin-specific proteases. Though this gene is located on the X chromosome, it escapes X-inactivation. Mutations in this gene have been associated with Turner syndrome. Alternate transcriptional splice variants, encoding different isoforms, have also been characterized.
Deubiquitinases play an important role regulatory role at the level of protein turnover by preventing degradation of proteins through the removal of conjugated ubiquitin and are an essential component of TGF-beta/BMP signaling cascade. They influence chromosome alignment and segregation in mitosis by regulating the localization of BIRC5/survivin to mitotic centromeres. Specifically hydrolyzing both 'Lys-29'- and 'Lys-33'-linked polyubiquitins chains and deubiquitinating mono-ubiquitinated SMAD4, opposing the activity of E3 ubiquitin-protein ligase TRIM33.