Regulation of protein degradation is required to ensure proper signaling and growth in all cells. For example, cells limit DNA replication to specific phases of growth by rapidly degrading proteins that trigger transitions between these phases. Improper degradation of DNA replication 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 harm the cell. The buildup 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.
However, protein degradation is a double-edged sword. Since it is irreversible, unregulated degradation would rapidly destroy all the proteins in the cell. How are certain proteins targeted for destruction while other proteins are not? How does the cell deploy protein degradation to maintain normal growth while responding to environmental changes?
The Protein Degradation subtheme investigates the biochemistry of protein degradation (Chien, Hardy) and the communication between protein chaperones and proteases (Gierasch), offering deep molecular insights into the mechanics of this process. Protein degradation is key to virulence in bacteria and understanding the degradation process in microbes (Chien, Gierasch) may open new avenues for antibiotic development. Finally, subcellular trafficking in eukaryotes is intimately dependent on the regulated destruction of cargo proteins (Hebert, Garman).