Protein Aggregation and Quality Control
Research Areas
Biochemistry and Molecular Biology
Protein Science
Protein Misfolding & Aggregation, Protein Homeostasis
Education
1987,
B.S., Department of Biology,
1990,
M.S., Department of Chemistry,
1993,
Ph. D., Shanghai Institute of Biochemistry,
Working Experience
1993-1994,
Assistant Professor, Shanghai Institute of Biochemistry,
1994-1996,
Postdoctoral, Department of Biochemistry, the Hong Kong
1996-2000,
Associate Professor, Shanghai Institute of Biochemistry,
2000, Visiting Scholar, Laboratory of NMR Structural Biology, Department of Biochemistry, University of Connecticut Health Center, USA;
2001-present,
Professor, Institute of Biochemistry & Cell Biology, Shanghai Institutes
for Biological Sciences,
2002-2003, Visiting Scholar, the Hong Kong University of Science & Technology, Hong Kong;
2004,
Visiting Scholar, Department of Molecular and Experimental Medicine, The
Scripps Research Institute,
Publications
Papers
[R] Hui Yang and Hong-Yu Hu*, Sequestration of cellular interacting partners by protein aggregates: implication in a loss-of-function pathology. FEBS J, 2016, 283: 3705-3717.
Hui Yang, Shuai Liu, Wen-Tian He, Jian Zhao, Lei-Lei Jiang and Hong-Yu Hu*, Aggregation of Polyglutamine-expanded Ataxin 7 Protein Specifically Sequesters Ubiquitin-specific Protease 22 and Deteriorates Its Deubiquitinating Function in the Spt-Ada-Gcn5-Acetyltransferase (SAGA) Complex. J Biol Chem, 2015, 290(36): 21996-22004.
Hui Yang, Jing-Jing Li, Shuai Liu, Jian Zhao, Ya-Jun Jiang, Ai-Xin Song, and Hong-Yu Hu*, Aggregation of polyglutamine-expanded ataxin-3 sequesters its specific interacting partners into inclusions: Implication in a loss-of-function pathology. Scientific Reports, 2014, 4: 6410.
Yong-Guang Gao*, Hui Yang, Jian Zhao, Ya-Jun Jiang, and Hong-Yu Hu*, Autoinhibitory Structure of the WW Domain of HYPB/SETD2 Regulates Its Interaction with the Proline-Rich Region of Huntingtin. Structure, 2014,22(3): 378-386.
Shuai Liu, Hui Yang, Yu-Hang Zhang, Ai-Xin Song, and Hong-Yu Hu*, NEDD8 ultimate buster-1 long (NUB1L) protein promotes transfer of NEDD8 to proteasome for degradation through the P97UFD1/NPL4 complex. J Biol Chem, 2013, 288(43):31339-31349.
Lei-Lei Jiang, Mei-Xia Che, Jian Zhao, Chen-Jie Zhou, Mu-Yun Xie, Hai-Yin Li, Jian-Hua He and Hong-Yu Hu*, Structural Transformation of the Amyloidogenic Core Region of TAR DNA Binding Protein of 43 kDa (TDP-43) Initiates Its Aggregation and Cytoplasmic Inclusion. J Biol Chem, 2013, 288(27): 19614-19624.
Xue-Chao Gao, Chen-Jie Zhou, Zi-Ren Zhou, Meng Wu, Chun-Yang Cao and Hong- Yu Hu*, The C-terminal Helices of Heat Shock Protein 70 Are Essential for J-domain Binding and ATPase Activation. J Biol Chem, 2012, 287(8): 6044-6052.
Zi-Ren Zhou, Yu-Hang Zhang, Shuai Liu, Ai-Xin Song and Hong-Yu Hu*, Length of the active-site crossover loop defines the substrate specificity of ubiquitin C-terminal hydrolases for ubiquitin chains. Biochem J, 2012, 441(1): 143-149.
Ya-Jun Jiang, Mei-Xia Che, Jin-Qiao Yuan, Yuan-Yuan Xie, Xian-Zhong Yan, and Hong-Yu Hu*, Interaction with Polyglutamine Expanded Huntingtin Alters Cellular Distribution and RNA Processing of Huntingtin Yeast Two-hybrid Protein A (HYPA). J Biol Chem, 2011, 286 (28): 25236-25245.
Mei-Xia Che, Ya-Jun Jiang, Yuan-Yuan Xie, Lei-Lei Jiang and Hong-Yu Hu*, Aggregation of the 35-kDa fragment of TDP-43 causes formation of cytoplasmic inclusions and alteration of RNA processing. FASEB J, 2011, 25 (7): 2344-2353.
Ai-Xin Song, Chen-Jie Zhou, Yu Peng, Xue-Chao Gao, Zi-Ren Zhou, Qing-Shan Fu, Jing Hong, Dong-Hai Lin* and Hong-Yu Hu*, Structural Transformation of the Tandem Ubiquitin-Interacting Motifs in Ataxin-3 and Their Cooperative Interactions with Ubiquitin Chains. PLoS ONE, 2010, 5 (10): e13202.
Xiao-Wei Zhang, Xiao-Jing Yan, Zi-Ren Zhou, Fei-Fei Yang, Zi-Yu Wu,，Hong-Bin Sun, Wen-Xue Liang, Ai-Xing Song, Lallemand-Breitenbach Valerie, Jeanne Marion, Qun-Ye Zhang, Huai-Yu Yang, Qiu-Hua Huang, Guang-Biao Zhou, Jian-Hua Tong, Yan Zhang, Ji-Hui Wu, Hong-Yu Hu, Hugues de Thé, Sai-Juan Chen*, Zhu Chen*, The Leukemia Drug Arsenic Trioxide Controls the Fate of the PML-RARa Oncoprotein by Directly Binding PML. Science, 2010, 328: 240-243.
Yuan-Yuan Xie, Chen-Jie Zhou, Zi-Ren Zhou, Jing Hong, Mei-Xia Che, Qing-Shan Fu, Ai-Xin Song, Dong-Hai Lin, and Hong-Yu Hu*, Interaction with synphilin-1 promotes inclusion formation of a-synuclein: Mechanistic insights and pathological implication. FASEB J, 2010, 24 (1): 196-205.
Qing-Shan Fu, Chen-Jie Zhou, Hong-Chang Gao, Ya-Jun Jiang, Zi-Ren Zhou, Jing Hong, Wen-Ming Yao, Ai-Xin Song, Dong-Hai Lin*, and Hong-Yu Hu*, Structural Basis for Ubiquitin Recognition by a Novel Domain from Human Phospholipase A2 Activating Protein. J Biol Chem, 2009, 284 (28): 19043-19052.
Yong-Gang Chang, Xian-Zhong Yan, Yuan-Yuan Xie, Xue-Chao Gao, Ai-Xin Song, Dong-Er Zhang and Hong-Yu Hu*, Different Roles for Two Ubiquitin-like Domains of ISG15 in Protein Modification. J Biol Chem, 2008, 283 (19): 13370-13377.
Yong-Guang Gao, Xian-Zhong Yan*, Ai-Xin Song, Yong-Gang Chang, Xue-Chao Gao, Nan Jiang, Qi Zhang, and Hong-Yu Hu*, Structural insights into the specific binding of huntingtin proline-rich region with SH3 and WW domains. Structure, 2006, 14 (12): 1755-1765.
Yong-Gang Chang, Ai-Xin Song, Yong-Guang Gao, Yan-Hong Shi, Xiao-Jing Lin, Xue-Tao Cao, Dong-Hai Lin*, Hong-Yu Hu*. Solution structure of the ubiquitin-associated domain of human BMSC-UbP and its complex with ubiquitin. Protein Sci, 2006, 15 (6): 1248-1259.
Hong-Tao Li, Dong-Hai Lin, Xiao-Ying Luo, Feng Zhang, Li-Na Ji, Hai-Ning Du, Guo-Qiang Song, Jun Hu, Jia-Wei Zhou and Hong-Yu Hu*. Inhibition of α-synuclein fibrillization by dopamine analogs via reaction with the amino groups of α-synuclein: Implication for dopaminergic neurodegeneration. FEBS J, 2005, 272 (14): 3661-3672.
Hong-Yu Hu, Julie K. Horton, Michael R. Gryk, Rajendra Prasad, Jana M Naron, Di-An Sun, Sidney M. Hecht, Samuel H. Wilson*, Gregory P Mullen, Identification of small molecule synthetic inhibitors of DNA polymerase beta by NMR chemical shift mapping. J Biol Chem, 2004, 279 (38): 39736-39744.
Hai-Ning Du, Lin Tang, Xiao-Ying Luo, Hong-Tao Li, Jun Hu, Jia-Wei Zhou, and Hong-Yu Hu*, A peptide motif consisting of glycine, alanine and valine is required for fibrillization and cytotoxicity of human a-synuclein. Biochemistry, 2003, 42 (29): 8870-8878.
Hongyu Hu*, Qi Li, Hongqiang Cheng, Haining Du, b-sheet structure formation of proteins in solid state as revealed by circular dichroism spectroscopy. Biopolymers, 2001, 62(1): 15-21.
Papers
Papers
Research Interests
The hallmark of some neurodegenerative diseases is the aggregation of abnormal proteins and formation of inclusion bodies in neural cells. The research group focuses on the mechanism of protein misfolding, amyloidogenic aggregation and biological degradation of these related proteins. Based on the biochemical and structural information, we are trying to understand the pathogenesis of the neurodegenerative diseases. The research areas are,
(1) Mechanism of protein misfolding, aggregation and inclusion formation, and their cellular effects;
(2) Sequestration of cellular normal proteins by protein aggregates and inclusions;
(3) NMR structural basis for and functional annotation of the molecular recognition involved in chaperone machinery and ubiquitin-proteasome degradation;
(4) Quality control of the amyloidogenic proteins associated with neurodegenerative diseases.