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院士风采
杰出青年
全所PI名录
 
 
地址:上海市岳阳路320号
邮编:200031
电话:86-21-54920000
传真:86-21-54921011
邮箱:sibcb@sibcb.ac.cn

全所PI名录 >

 
胡红雨
研究员,研究组长,博士生导师
E-mail: hyhu@@sibs.ac.cn


个人简介

1987年毕业于复旦大学生物系,1990年复旦大学化学系硕士学位,1993年获中科院上海生化所博士学位。1993-1994年任中科院上海生化所助研,1994-1996年在香港科技大学生化系做博士后研究。1996-2000年任中科院上海生化所副研究员,2000年6-12月在美国康涅狄格大学医学中心NMR结构生物学实验室做访问学者。2001年起任中科院上海生化与细胞所研究员, 2012年晋升为二级研究员。2002年10月-2003年4月香港科技大学生化系访问学者。2004年9月-12月美国Scripps研究所分子与实验医学系访问学者。现为国际刊物Scientific Reports, Protein & Peptide Letters和Acta Biochem. Biophys. Sinica编委。


研究方向

蛋白质错误折叠及质量控制


研究工作
关键词:蛋白质, 错误折叠, 质量控制,神经退行性疾病;积聚和包涵体,降解作用,分子伴侣,泛素-蛋白酶体;相互作用,结构与功能,核磁共振,荧光。
        蛋白质错误折叠、淀粉样积聚和降解作用的分子机制及与神经退行性疾病的关系。神经退行性疾病(如帕金森症)的发生与神经细胞内的蛋白质的错误折叠、异常积聚和包涵体形成有关。本课题组着重研究神经退行性疾病相关的蛋白质的错误折叠、淀粉样积聚和生物降解作用的分子机制。在结构信息基础上,结合现代生命科学的研究成果理解细胞内蛋白质错误折叠、淀粉样化积聚和生物降解的效应及与神经退行性疾病发生的联系。用核磁共振和其它结构分析法解析蛋白质异常积聚和生物降解过程中的蛋白质或特定结构域的空间结构和这些蛋白质间的相互作用以及生物功能。
        课题组将结合生物化学、分子生物学、结构生物学和细胞生物学的原理和方法研究蛋白质的错误折叠和降解的分子机制及与神经退行性疾病发生的联系。将以神经退行性疾病相关的蛋白质为对象,研究蛋白质的错误折叠、积聚和包涵体形成,分子伴侣和辅伴侣的作用,以及细胞内蛋白质的降解过程。课题组重点关注的科学问题是:蛋白质为什么会发生错误折叠和积聚; 蛋白质错误折叠和积聚有什么细胞效应; 以及细胞是如何清除蛋白质积聚物或包涵体的。我们目前感兴趣的主要研究方向:(1) 淀粉样蛋白质的结构转换、积聚和包涵体形成的分子机制,抑制蛋白质异常积聚的化合物及抑制作用机理;(2)蛋白质积聚所形成的包涵体对细胞内正常蛋白质的募集作用;(3)泛素-蛋白酶体降解和分子伴侣途径中蛋白质相互作用和分子识别的NMR结构基础及生物功能;(4)神经退行性疾病相关的细胞内蛋白质质量控制。


代表性论文

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.

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