Targeting protein ubiquitination for drug discovery. What is in the drug discovery toolbox?
Protein ubiquitination regulates the half-lives of many proteins by targeting them for degradation. Ubiquitination is a specific process associated with several highly regulated biological outcomes including cell cycle progression, differentiation, antigen presentation, retrovirus assembly, apoptosis, signal transduction, transcriptional activation, biological clocks, receptor downregulation and endocytosis. Newly discovered families of ubiquitination and deubiquitination enzymes participate in these processes. These enzymes could provide new families of drug targets and new ways of intervention in many human diseases; however, much work is required to validate this approach. This review will discuss what is in the drug discovery toolbox to assist in the validation of ubiquitination enzymes as therapeutic targets.
Swinney
D C.
DC
Inflammatory Diseases Unit, Roche Bioscience, -94303, Palo Alto, CA, USA