Home CAS Center for Excellence
  
  
  

Faculty

Members of CAS, CAE
National Outstanding Young Scientists Award
Principal Investigators
 
Address: 320 Yue Yang Road, Shanghai 200031, P.R. China
Tel: 86-21-54920000
Fax: 86-21-54921011
Email: sibcb@sibs.ac.cn
Website: www.sibcb.ac.cn
 
Principal Investigators
 
LI Lin
Ph.D., Professor
Member of CAS
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China.
Email: lli@@sibs.ac.cn

Research Areas
Wnt signalling; LRP5/6-Axin; Caprin-2; ZBED3; Myogenesis;beta-catenin-I-mfa; Transcriptional activation; Dvl-c-Jun; yeast two-hybrid; phosphoproteomics; zebrafish; rhodopsin/GRKs; ROCK/PTEN

Research Interests
Our laboratory has a long-standing interest in understanding the molecular mechanisms of Wnt signaling pathway. One part is focused on how the endogenous signal molecules cooperate in a multi-component complex manner in specific signal events, which we now concentrate mainly on signal processes nearby the cell membrane or in nucleus. Another part, we are also interested in how Wnt signal play roles in developing embryo and ES cells directional differentiation, and investigate the molecular basis of Wnt signaling function at the level of the organism. In addition, as it have been reported aberrantly activated Wnt leads to cancer, we wish to find out, based on a high-throughput screen, novel small-molecules which may downregulate Wnt signal especially at downstream of β-catenin stabilization and, simultaneously, reveal the potential targets for cancer treatment.

Selected Publications

  1. Chao Wang, Wenxiang Zhang, Meng-Xin Yin, Lianxin Hu, Peixue Li, Jiajun Xu, Hongling Huang, Shimin Wang, Yi Lu, Wenqing Wu, Margaret S. Ho, Lin Li, Yun Zhao, and Lei Zhang* (2015) Suppressor of Deltex mediates Pez degradation and modulates Drosophila midgut homeostasis. Nature Communications, in press.
  2. Jia Shen, Xiangpeng Sheng, ZeNan Chang, Qian Wu, Sheng Wang, Zongliang Xuan, Dan Li, Yalan Wu, Yongjia Shang, Xiangtao Kong, Long Yu, Lin Li, Kangchen Ruan, Hongyu Hu, Ying Huang, Lijian Hui, Dong Xie, Fudi Wang, and Ronggui Hu* (2014) Iron metabolism regulates p53 signaling through direct heme-p53 interaction and modulation of p53 localization, stability, and function. Cell Reports, 7, 1-14.
  3. Zhengzhao Liu, Peng Chen, Hong Gao, Yu Gu, Jiao Yang, Hong Peng, Xingxing Xu, Haifeng Wang, Meiqiang Yang, Xiaoying Liu, Libin Fan, Shiyao Chen, Jian Zhou, Yihong Sun, Kangchen Ruan, Shuqun Cheng, Masaaki Komatsu, Eileen White, Lin Li, Hongbin Ji, Daniel Finley, Ronggui Hu* (2014) Ubiquitylation of autophagy receptor optineurin. Cancer Cell, 26, 106-120.
  4. Xiaomin Song, Sheng Wang, and Lin Li* (2014) New insights into the regulation of Axin function in canonical Wnt signaling pathway. Protein & Cell, 5, 186-193
  5. Ying-ying Jia, Fen Nie, Ai-ying Du, Zhang-cheng Chen, Yuan-bo Qin, Tao Huang, Xiao-min Song, and Lin Li* (2014) Thymine DNA glycosylase promotes transactivation of b-catenin/TCFs by cooperating with CBP. J. Mol. Cell Biol., 6, 231-239
  6. Haofei Miao, Yingying Jia, Sichun Xie, Xin Wang, Jianfei Zhao, Youjun Chu, Zhilei Zhou, Zhubing Shi, Xiaomin Song*, and Lin Li* (2014) Structural insights into the C1q domain of Caprin-2 in canonical Wnt signaling. J. Biol. Chem., 289, 34104C34113
  7. Cong Fei*, Xiaoli He, Sichun Xie, Haofei Miao, Zhilei Zhou, and Lin Li* (2014) Smurf1-mediated Axin ubiquitination requires Smurf1 C2 domain and is cell-cycle dependent. J. Biol. Chem., 289, 14170-14177
  8. Sheng Wang, Junlin Yin, Duozhi Chen, Fen Nie, Xiaomin Song, Cong Fei, Haofei Miao, Changbin Jing, Wenjing Ma, Lei Wang, Sichun Xie, Chen Li, Rong Zeng, Weijun Pan, Xiaojiang Hao*, and Lin Li* (2013) Small-molecule modulation of Wnt signaling via modulating the Axin-LRP5/6 interaction. Nature Chem. Biol., 9, 579-585.
  9. Chun-Xiao Song, Keith E. Szulwach, Qing Dai, Ye Fu, Shi-Qing Mao, Li Lin, Craig Street, Yujing Li, Mickael Poidevin, Hao Wu, Juan Gao, Peng Liu, Lin Li, Guo-Liang Xu, Peng Jin, and Chuan He (2013) Genome-wide profiling of 5-formylcytosine reveals its roles in epigenetic priming. Cell, 153, 678-691.
  10. Cong Fei, Zhenfei Li, Chen Li, Yuelei Chen, Zhangcheng Chen, Xiaoli He, Li Mao, Xin Wang, Rong Zeng, and Lin Li* (2013) Smurf1-mediated Lys29-linked non-proteolytic poly-ubiquitination of Axin negatively regulates Wnt/β-catenin signaling. Mol. Cell Biol., 33, 4095-4105.
  11. Wei Wei, Meng Li, Jiyong Wang, Fen Nie and Lin Li* (2012) The E3 ubiquitin ligase ITCH negatively regulates canonical Wnt signaling by targeting dishevelled protein. Mol. Cell Biol., 32, 3903-3912.
  12. Yu-Fei He, Bin-Zhong Li, Zheng Li, Peng Liu, Yang Wang, Qingyu Tang, Jianping Ding, Yingying Jia, Zhangcheng Chen, Lin Li, Yan Sun, Xiuxue Li, Qing Dai, Chun-Xiao Song, Kangling Zhang, Chuan He, and Guo-Liang Xu (2011) Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science, 333, 1303-1307.
  13. Tao Huang, Zhihui Xie, Jiyong Wang, Meng Li, Naihe Jing, and Lin Li* (2011) Nuclear Factor of Activated T Cell (NFAT) Proteins repress canonical Wnt signaling via its interaction with dishevelled (Dvl) protein and participate in regulating neural progenitor cell proliferation and differentiation. J. Biol. Chem., 286, 37399-37405.
  14. Wenwen Tang, Yong Zhang, Wenwen Xu, T. Kendall Harden, John Sondek, Le Sun, Lin Li, and Dianqing Wu* (2011) A PLCb/PI3Kg-GSK3 signaling pathway regulates cofilin phosphatase Slingshot2 and neutrophil polarization and chemotaxis. Dev. Cell, 21, 1038-1050.
  15. Zhihui Xie, Yongfeng Chen, Zhenfei Li, Ge Bai, Yue Zhu, Rui Yan, Fangzhi Tan, Ye-Guang Chen, Francois Guillemot, Lin Li, and Naihe Jing (2011) Smad6 promotes neuronal differentiation in the intermediate zone of the dorsal neural tube by inhibition of the Wnt/b-catenin pathway. Proc. Natl. Acad. Sci. USA, 108, 12119-12124.
  16. Zhenfei Li, Fen Nie, Sheng Wang, and Lin Li* (2011) Histone H4 Lys 20 monomethylation by histone methylase SET8 mediates Wnt target gene activation. Proc. Natl. Acad. Sci. USA, 108, 3116-3123.
  17. Wei Wang, Haiyang Liu, Sheng Wang, Xiaojiang Hao*, and Lin Li* (2011) A diterpenoid derivative 15-oxospiramilactone inhibits Wnt/b-catenin signaling and colon cancer cell tumorigenesis. Cell Res., 21, 730-740.
  18. Meng Li, He Wang, Tao Huang, Jiyong Wang, Yu Ding, Zhenfei Li, Jinkuo Zhang, and Lin Li* (2010) TAB2 scaffolds TAK1 and NLK in repressing canonical Wnt signaling. J. Biol. Chem., 285, 13397-13404.
  19. Ning Deng, Yanger Ye, Wei Wang, and Lin Li* (2010) Dishevelled interacts with p65 and acts as a repressor of NF-kB-mediated transcription. Cell Res., 20, 1117-1127.
  20. Bianhong Zhang, Meng Li, Liang Chen, Kai Yang, Yufei Shan, Lianhui Zhu, Shaogang Sun, and Lin Li*, and Chen Wang* (2009) The TAK1-JNK cascade is required for IRF3 function in the innate immune response. Cell Res., 19, 412-428.
  21. Ting Chen, Meng Li, Yu Ding, Leshuai Zhang, Ying Xi, Weijun Pan, Donglei Tao, Jiyong Wang, and Lin Li* (2009) Identification of zinc-finger bed domain containing 3 (ZBED3) as a novel axin-interacting protein that activates Wnt/b-catenin signaling. J. Biol. Chem., 284, 6683-6689.
  22. Weijun Pan, Sun-Cheol Choi, He Wang, Yuanbo Qin, Laura Volpicelli-Daley, Laura Swan, Louise Lucast, Cynthia Khoo, Xiaowu Zhang, Lin Li, Charles S. Abrams, Sergei Y. Sokol, and Dianqing Wu (2008) Wnt3a-mediated formation of phosphatidylinositol 4,5-bisphosphate regulates LRP6 phosphorylation. Science, 321, 1350-1353.
  23. Yu Ding, Ying Xi, Ting Chen, Ji-yong Wang, Dong-lei Tao, Zhi-li Wu, Yi-ping Li, Chen Li, Rong Zeng, and Lin Li* (2008) Caprin-2 enhances canonical Wnt signaling through regulating LRP5/6 phosphorylation. J. Cell Biol., 182, 865-872.
  24. Xiao-qing Gan, Ji-yong Wang, Ying Xi, Zhi-li Wu, Yi-ping Li, and Lin Li* (2008) Nuclear Dvl, c-Jun, b-catenin and TCF form a complex leading to stabilization of b-catenin/TCF interaction. J. Cell Biol., 180, 1087-1100.
  25. Weijun Pan, Yingying Jia, Tao Huang, Jiyong Wang, Donglei Tao, Xiaoqing Gan, and Lin Li* (2006) b-Catenin relieves I-mfa-mediated suppression of LEF-1 in mammalian cells. J. Cell Sci., 119, 4850-4856.
  26. Weijun Pan, Yingying Jia, Jiyong Wang, Donglei Tao, Xiaoqing Gan, Leonidas Tsiokas, Naihe Jing, Dianqing Wu, and Lin Li* (2005) b-Catenin regulates myogenesis by relieving I-mfa-mediated suppression of myogenic regulatory factors in P19 cells. Proc. Natl. Acad. Sci. USA, 102, 17378-17383.  
  27. Zhong Li, Xiemei Dong, Zhenglong Wang, Wenzhong Liu, Ning Deng, Yu Ding, Liuya Tang, Tim Hla, Rong Zeng, Lin Li*, and Dianqing Wu* (2005) Regulation of PTEN by Rho small GTPases. Nature Cell Biol., 7, 399-407. 
  28. Xiaoqing Gan, Zhihai Ma, Ning Deng, Jiyong Wang, Jianping Ding, and Lin Li* (2004) Involvement of the C-terminal proline-rich motif of G protein coupled receptor kinases in recognition of activated rhodopsin. J. Biol. Chem., 279, 49741-49746.
  29. Weijun Pan, Shuzhao Pang, Tao Huang, Huiyun Guo, Dianqing Wu, and Lin Li* (2004) Characterization of function of three domains in dishevelled-1: DEP domain is responsible for membrane translocation of dishevelled-1. Cell Res., 14, 324-330.
  30. Lin Li*, Junhao Mao, Le Sun, Wenzhong Liu & Dianqing Wu* (2002) Second cysteine-rich domain of dickkopf-2 activates canonical Wnt signaling pathway via LRP-6 independently of dishevelled. J. Biol. Chem., 277, 5977-5981.
  31. Junhao Mao, Jiyong Wang, Bo Liu, Weijun Pan, Gist H. Farr III, Christopher Flint, Huidong Yuan, Shinji Takada, David Kimelman, Lin Li* & Dianqing Wu* (2001) Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway. Mol. Cell, 7, 801-809.
  32. Qi-heng Yang, Zheng Zhu, Meng-qiu Dong, Song Ling, Chun-lai Wu & Lin Li* (2001) Binding of ATP to the fructose-2,6-bisphosphatase domain of chicken liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase leads to activation of its 6-phosphofructo-2-kinase. J. Biol. Chem., 276, 24608-24613.
  33. Xiao-qing Gan, Ji-yong Wang, Qi-heng Yang, Zhong Li, Feng Liu, Gang Pei & Lin Li* (2000) Interaction between the conserved region in the C-terminal domain of grk2 and rhodopsin is necessary for grk2 to catalyze receptor phosphorylation. J. Biol. Chem., 275, 8469-8474.

Education Background & Academic Experience
Lin Li, Ph.D., Professor, Executive Director of Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (CAS). He was graduated from the Department of Biology, Nanjing University in 1983 and obtained Ph.D degree in 1989 at former Shanghai Institute of Biochemistry, CAS. From 1990 to 1992 he worked as a postdoctoral research associate at Department of Physiology and Biophysics, SUNY at Stony Brook. He was appointed as associate professor by Shanghai Institute of Biochemistry in 1991, and then professor in 1993.

Research Team

 

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