Many studies have focused on the role of new protein synthesis in cardioprotection, but much less is known regarding the importance of protein degradation in the heart’s susceptibility to ischemic injury. A primary mechanism of protein degradation in cardiac and other cell types is the ubiquitin-proteasome system. In this system, a series of enzymes target a given protein for degradation by attachment of a chain of ubiquitins, and the protein is then proteolzyed by the proteasome, a multiprotein complex composed of approximately 46 subunits.

Our laboratory has started investigating the importance of ubiquitin-proteasome-dependent degradation of proteins as a mechanism of cardioprotective signaling. We are utilizing functional proteomics to investigate the 20S and 26S proteasome complex in the normal, protected, and diseased heart. In particular, we are interested in the role of post-translational modifications of the proteasome on the physiological function of the proteasome.