title: Deubiquitinating enzyme inhibitors and their potential in cancer therapy.
abstract: Deubiquitinating enzymes (or DUBs) attack the ubiquitin-based isopeptide bond, thus counteracting ubiquitinprotein ligase activity in vivo. By disassembling ubiquitin-substrate and ubiquitin-ubiquitin covalent links, deubiquitinating enzymes exert a very powerful control of many signaling processes within the ubiquitin-proteasome system (UPS). Very active research in this field in the last decade shows that deubiquitinating enzymes play important regulatory roles in aspects relevant to cancer, such as proteasome activity, p53 stability, the regulation of fanconi anemia related proteins, tumor cell apoptosis induction, to mention a few. Thus, deubiquitinating enzymes have emerged as interesting drug targets in cancer research. Here, the pharmacological inhibition of DUBs and its potential effect in cancer treatment are reviewed.
authors.affiliation: Institut de Biologia Molecular de Barcelona, CSIC, Barcelona Science Park, Baldiri i Reixac 4, 08028 Barcelona, Spain. bernat.crosas@ibmb.csic.es.
authors.forename: Bernat
authors.initials: B
authors.lastname: Crosas
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D059748:Proteolysis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D064570:Ubiquitin-Specific Proteases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D061988:Proteasome Inhibitors; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D064570:Ubiquitin-Specific Proteases; D046988:Proteasome Endopeptidase Complex