Nei-Li Chan
Affiliations
Institute of Biochemistry & Molecular Biology, National Taiwan University
Biography
Nei-Li Chan received a BSc degree in Chemistry in 1991 from National Taiwan University, Taiwan. After two years of compulsory military service as a Second Lieutenant in the Taiwanese Army, he enrolled in the Biochemistry doctoral program offered by the University of Iowa (USA) and completed his PhD degree in 1998. From 1999 to 2001, he conducted post-doctoral training with Prof. Chris Hill (University of Utah, USA).
He then returned to Taiwan and joined the faculty of National Chung Hsing University. He moved to National Taiwan University in 2007, where he is currently appointed as a Professor of Biochemistry and Molecular Biology. He uses various biochemical and biophysical techniques, including X-ray crystallography, to study the structure and function of proteins. In recent years, he has been actively engaged in the “structural-based design of isozyme-selective type II topoisomerase-targeting anticancer agents” and the elucidation of “structural basis of antizyme-mediated proteosomal degradation pathway”.
Abstract
Structural Basis of Antizyme-Mediated Regulation of Polyamine Homeostasis
Hsiang-Yi Wu, Shin-Fu Chen, Ju-Yi Hsieh, Shiou-Ru Tzeng, Hui-Chih Hung, & Nei-Li Chan
Polyamines are organic polycations essential for cell growth and differentiation. To maintain polyamine homeostasis, the activity/abundance of ornithine decarboxylase (ODC), the committed enzyme for polyamine biosynthesis, are reciprocally controlled by antizyme (Az) and antizyme inhibitor (AzIN). We have determined the structures of human Az complexed with either ODC or AzIN.
Structural analysis revealed that Az sterically blocks ODC homodimerization and triggers ODC degradation by exposing a cryptic proteasome-interacting surface, illustrating how a protein is primed for ubiquitylation-independent proteasome recognition. Dynamic and functional analyses indicated the Az-induced binding and degradation of ODC by proteasome can be decoupled. The AzIN-Az structure suggests how AzIN competes with ODC for Az to restore polyamine production. Our studies offer structural insights into the Az-mediated regulation of polyamine homeostasis and proteasomal degradation.
