Peter Chien

All biological systems rely on protein synthesis and degradation (proteolysis). Regulation of proteolysis is needed to ensure proper signaling and growth in all cell types. For example, cells limit DNA replication to specific phases of growth by rapidly degrading factors that trigger transitions between these phases. The improper degradation of these factors results in pathological conditions like cancer. In addition, chemical or environmental shocks can generate toxic, damaged proteins that must be eliminated before they can cause harm to the cell. The buildup of these types of damaged proteins is a hallmark of many neurological diseases such as Alzheimer's and Huntington's diseases, further illustrating the importance of properly regulating protein degradation.

Protein degradation is a double-edged sword. Since protein degradation is irreversible, unregulated proteolysis would rapidly destroy all the proteins in the cell. However, the cell must have a robust way to rapidly degrade those proteins that are unwanted. Therefore, regardless of the specific organism or system, there are fundamental questions common to all proteolysis pathways. How are certain proteins targeted for destruction while other proteins are not? How does the cell regulate proteolysis to maintain normal growth while responding to environmental changes?