Deciphering the Ubiquitin-Proteasome System

All of the proteins in our bodies have distinct lifespans and are continuously recycled. This recycling is essential for our health. Proteins that need to be eliminated from cells are covalently modified with a specific ubiquitin tag by the ubiquitin system. This tag is then recognized by the proteasome which selectively degrades tagged proteins. Dysregulation of this ubiquitin-proteasome system (UPS) can cause cancers, neurodegenerative diseases, and aging.

Therefore, there is currently a worldwide effort to identify drugs that modulate activity of this system. In our laboratory, we focus on glycoprotein-specific ubiquitin ligases which are associated with diseases caused by abnormal glycoprotein metabolism. We are also identifying drugs that modulate activity of these ligases and studying the dynamics and functions of the proteasome and ubiquitin ligases under conditions of cellular stress.