Grant: Operating Grant

Ubiquitin is a small protein that is used to tag many important regulatory factors in the cell for destruction or other regulatory fates. Ubiquitin is attached to many thousands of target proteins through the precisely controlled action of a complex enzymatic cascade. These attachment processes are essential for all aspects of normal cellular function. Recently, it has become apparent that the ubiquitin system is misregulated in most if not all human cancers. First generation drugs directed against the ubiquitin system have demonstrated enormous potential in cancer therapy. In this proposal, we will investigate the role of specific enzymes that catalyze ubiquitin attachment in important cellular processes implicated in cancer formation, and develop new potential therapeutic lead compounds that specifically rectify aberrations of the ubiquitin system in cancer cells.