Ruey-Hwa Chen
Affiliations
Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
Biography
Dr. Ruey-Hwa Chen received a Ph.D. degree at Michigan State University (1991) and was a Postdoctoral Fellow and Assistant Biochemist at UCSF (1992-1996). She then became an Associate Professor and Professor at Institute of Molecular Medicine, National Taiwan University. In 2006, she relocated to Institute of Biological Chemistry, Academia Sinica to be a Research Fellow and promoted to Distinguished Research Fellow in 2012. She served as a Deputy Director of Institute of Biological Chemistry from 2011 to 2013. She holds an Adjunct Professorship at National Taiwan University and an Adjunct Chair Professorship at China Medical University. Her research focuses on protein ubiquitination in tumor progression, autophagy regulation, and intracellular trafficking. She has received a number of awards, including Outstanding Young Investigator Award and Investigator Award (twice) from Academia Sinica, Outstanding Research Award from National Science Council (three times), Outstanding Award from TienTe Lee Biomedical Foundation, and TBF Chair in Biotechnology.
Abstract
Ubiquitination controls autophagy termination
Ruey-Hwa Chen
Autophagy, a cellular self-eating mechanism, is important for maintaining cell survival and tissue homeostasis in response to various stressed conditions. Although the mechanism of autophagy induction has been well studied, it remains elusive how cells terminate the autophagy process once it has been induced. KLHL20 is a substrate adaptor of Cullin3 (Cul3)-family ubiquitin ligase. Here, we show that ULK1, a serine/threonine kinase critical for autophagy initiation, is a substrate of Cul3-KLHL20 complex. In response to autophagy induction, ULK1 autophosphorylation at S1042/T1046 stimulates its interaction with KLHL20, thereby increasing ULK1 ubiquitination and proteolysis.
This autophagy-induced, KLHL20-dependent ULK1 degradation controls the amplitude and duration of autophagy to prevent prolonged and overly activated autophagy. Additionally, KLHL20 governs the degradation of ATG13, VPS34, Beclin-1, and AMBRA1 in prolonged starvation through direct or indirect mechanisms. Together, our study identifies an important autophagy termination mechanism mediated by KLHL20-dependent turnover of ULK1 and VPS34 complex components.
