The ubiquitin-proteasome system plays a critical role in controlling the level, 
activity and location of various cellular proteins. Significant progress has 
been made in investigating the molecular mechanisms of ubiquitination, 
particularly in understanding the structure of the ubiquitination machinery and 
identifying ubiquitin protein ligases, the primary specificity-determining 
enzymes. Therefore, it is now possible to target specific molecules involved in 
ubiquitination and proteasomal degradation to regulate many cellular processes 
such as signal transduction, proliferation and apoptosis. In particular, 
alterations in ubiquitination are observed in most, if not all, cancer cells. 
This is manifested by destabilization of tumor suppressors, such as p53, and 
overexpression of oncogenes such as c-Myc and c-Jun. In addition to the 
development and clinical validation of proteasome inhibitor, bortezomib, in 
myeloma therapy, recent studies have demonstrated that it is possible to develop 
inhibitors for specific ubiquitination and deubiquitination enzymes. With the 
help of structural studies, rational design and chemical synthesis, it is 
conceivable that we will be able to use 'druggable' inhibitors of the ubiquitin 
system to evaluate their effects in animal tumor models in the not-so-distant 
future.