Deubiquitinating Enzyme Inhibitors and their Potential in Cancer Therapy

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. Keywords: Deubiquitinating enzymes, DUBs, inhibitors, proteasome, small-molecule, ubiquitin specific proteases, USP1, USP7, USP8, USP9x, USP14.