Welcome

Welcome to the website for the laboratory of George N. DeMartino, Ph.D., at UT Southwestern Medical Center.

The general interest of our laboratory is the study of biochemical mechanisms and physiological regulation of intracellular protein degradation. Our research focuses principally on the ubiquitin-proteasome system, a complex proteolytic system responsible for many aspects of protein degradation in eukaryotic cells.

Intracellular protein degradation is a fundamental and extensive process in all living cells. Cells utilize protein degradation as a mechanism to regulate many processes including transcription, progression of the cell cycle, flux of metabolites through metabolic pathways, signaling pathways, net growth and atrophy, and protein quality control. Because regulated protein degradation is essential for normal cellular function, it is not surprising that many human diseases involve altered protein degradation. Such diseases include many types of cancer, tissue wasting diseases, and neurodegenerative diseases. Consequently, components of protein degradation pathways are targets of drug therapy.

Proteasome

The proteasome is a complex molecular machine responsible for most intracellular protein degradation in eukaryotic cells. The Proteasome is composed of multiple subunits and multiple multisubunit subcomplexes.

Protein Degradation

Intracellular protein degradation is an extensive process in all cells. It performs many essential roles for the normal growth, development and regulation of cells. Protein degradation controls critical processes by setting cellular levels of critical regulatory proteins. For example, protein degradation controls the cell cycle, transcription, signal transduction, and the flux of substrates through metabolic pathways by eliminating proteins that are required for activation of inhibition of these processes. Moreover, the regulation of global rates of protein degradation determines the net growth or atrophy of whole tissues.

The number of cellular processes and proteins controlled by regulated proteolysis probably rivals that controlled by regulated phosphorylation. Defects in protein degradation have important medical consequences and lead to many human pathologies including cancer, muscle wasting diseases, neurological diseases, and metabolic diseases. Therefore, components of proteolytic pathways are active targets for drug therapy.

Reference

Kircher, M. Trends Biochem. Sci. M42-M44