Deubiquitinating Enzymes as Novel Targets for Cancer Therapies

Most ubiquitinated proteins can be recognized and degraded by the 26S proteasome. In the meantime, protein deubiquitination by various deubiquitinating enzymes (DUBs) regulates protein stability within cells, and it can counterbalance intracellular homeostasis mediated by ubiquitination. Numerous reports have demonstrated that an aberrant process of the ubiquitin-proteasome pathway (UPP) regulated by the ubiquitination and deubiquitination systems results in failure of balancing between protein stability and degradation, and this failure can lead to tumorigenesis in various organs and tissues of mammals. The identification of molecular properties for various DUBs is very critical to understand cancer development and tumorigenesis. Therefore, knowledge of DUBs and their association with cancer and diseases is indispensible for developing effective inhibitors for DUBs. This chapter describes various features and functions of cancer-related DUBs. In addition, we summarize several inhibitors that specifically target certain DUBs in cancer and suggest that DUBs may be one of the most ideal and attractive therapeutic targets.