Review Article Isopeptidases in anticancer therapy: looking for inhibitors
Andrea Sgorbissa, Harish Potu, Claudio Brancolini
Dipartimento di Scienze e Tecnologie Biomediche (DSTB), Università degli Studi di Udine, p.le Kolbe 4 3100 Udine ITALY.
Received April 29, 2010; accepted May 6, 2010, available online May 10, 2010
Abstract: Addition of polypeptides belonging to the ubiquitin family to selected lysines residues is a widespread post-translation modification (PTM) that controls many fundamental aspects of cell’s life. Specific alterations in the normal turnover of this PTM are frequently observed in tumors. The conjugation/deconjugation cycle of ubiquitin (Ub) or ubiquitin-like (Ubl) proteins influences the activities of oncogenes and tumor suppressor genes. Two families of enzymes work in antagonizing manner to add or remove Ub and Ubl-proteins on target proteins: the E3 ligases and the isopeptidases. These enzymes are the subjects of fervent research with the ambition to comprehend their regulation, their mechanisms of action, their involvement in human diseases, and to develop specific inhibitors for therapeutic intervention. Here we will discuss of isopeptidases, the deconjugating enzymes, with particular emphasis on the pro-apoptotic activities of the relative inhibitors identified so far. (AJTR1004006).