Dr. Yihong Ye, senior investigator of Protein Stability and Quality Control Section in NIDDK, gave a lecture on “Protein quality control in and out of the ER” as part of ShanghaiTech’s Life Science Seminar Series on April 27, 2016.
Dr.Yihong had a long-standing interest in understanding how cells deal with misfolded proteins in the endoplasmic reticulum (ER) and other cellular compartments. Polypeptides entering the ER may frequently encounter folding problems, resulting in aggregation-prone misfolded proteins. To preserve ER homeostasis, eukaryotes have evolved a conserved quality control pathway termed ERAD, which eliminates misfolded or damaged proteins of the ER by exporting them into the cytoplasm for degradation by the ubiquitin proteasome system. Dr. Yihong and his lab reported the function of p97 in ERAD pathway for the first time. In his report, Dr.Yihong shared us with the new research progress of his lab on the function of deubiquitinating enzyme USP19. They found that USP19 might mediate misfolded proteins secreted to extracellular to alleviate cell stress. These results indicating a novel protein quality control mechanism for cells under ER stress.
Defects in protein quality control system have been associated with pathogenesis of many human diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. Many proteins involved in the ERAD are now being considered as potential drug targets for treatment of cancer and neurodegenerative diseases. The work of Dr.Yihong‘s lab may allow us to design small molecule inhibitors that can either enhance or disrupt the ERAD system, which may be used to treat human diseases.
