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Faculty

Principal Investigators
State Key Laboratory of Molecular Biology
State Key Laboratory of Cell Biology
Center for Cell Signaling
National Center for Protein Science Shanghai
Members of CAS, CAE
Ten Thousand Talent Program Recipients
Thousands Talent Program Recipients
National Outstanding Young Scientists Award
Innovative Group
100 Talents Program of the CAS
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
ZHOU Zhaocai
Ph.D., Professor
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China.
Tel: 021-54921291
Email: zczhou@@sibcb.ac.cn

Research Areas
Signaling Mechanisms of Immunity

Research Interests
Our primary research interest is to understand the principle of immune responses and tumor immunology at multiple levels (Figure 1). We combine biochemical and structural analyses with cell signaling, animal models and clinical relevance to explore the function and molecular mechanisms of protein/DNA complexes and pathways that are critical for both immunity and tumorigenesis (Figure 2). In addition to dissecting the nature of these fundamental physiological or pathological processes, we also aim to further discover new drug targets and design novel therapeutic strategies for disease treatment.

Figure 1
Figure 2

Selected Publications

  1. Zhubing Shi, Shi Jiao and Zhaocai Zhou. STRIPAK complexes in cell signaling and cancer. Oncogene, 2016, 1-9 (Invited Review)
  2. Xiangdong Lv, Zhijun Han, Hao Chen, Bo Yang, Xiaofeng Yang, Yuanxin Xia, Chenyu Pan, Lin Fu, Shuo Zhang, Hui Han, Min Wu, Zhaocai Zhou, Lei Zhang, Lin Li, Gang Wei and Yun Zhao. A positive role for polycomb in transcriptional regulation via H4K20me1. Cell Res, 2016, 26: 529-542
  3. Ke Xu, Haifeng Liu, Zhubing Shi, Guangrong Song, Xiaoyan Zhu, Yuzhang Jiang, Zhaocai Zhou and Xiaolong Liu. Disruption of the RAG2 zinc finger motif impairs protein stability and causes immunodeficiency. Eur J Immunol, 2016, 46: 1011-1019
  4. Congcong Wang, Xianglu Zeng, Zhaocai Zhou, Jian Zhao & Gang Pei. -arrestin-1 contributes to brown fat function and directly interacts with PPAR and PPAR. Sci Rep, 2016, doi:10.1038/srep26999
  5. Qian Hao, Shi Jiao, Zhubing Shi, Chuanchuan Li, Xia Meng, Zhen Zhang, Yanyan Wang, Xiaomin Song, Wenjia Wang, Rongguang Zhang, Yun Zhao, Catherine CL Wong, Zhaocai Zhou. A Non-canonical Role of the p97 Complex in RIG-I Antiviral Signaling. EMBO J, 2015, 34: 2903-2920 (Highlighted by Science Signaling and F1000Prime)
  6. Shi Jiao, Zhen Zhang, Chuanchuan Li, Min Huang, Zhubing Shi, Yanyan Wang, Xiaomin Song, Heng Liu, Chunyang Li, Min Chen, Wenjia Wang, Yun Zhao, Zhengfan Jiang, Hongyan Wang, Catherine CL Wong, Chen Wang, Zhaocai Zhou. The kinase MST4 limits inflammatory responses through direct phosphorylation of the adaptor molecule TRAF6. Nat Immunol, 2015, 16: 246-257 (Highlighted by Science Signaling)
  7. Zhubing Shi, Zhen Zhang, Zhenzhen Zhang, Yicui Wang, Chuanchuan Li, Xin Wang, Feng He, Lina Sun, Shi Jiao, Weiyang Shi, Zhaocai Zhou. Structural Insights into Mitochondrial Antiviral-Signaling Protein (MAVS)-Tumor Necrosis Factor Receptor-Associated Factor 6 (TRAF6) Signaling. J Biol Chem. 2015, 290: 26811-20
  8. Zhao Zhang, Yanyan Wang, Chuanchuan Li, Zhubing Shi, Qiao Hao, Wenjia Wang, Xiaomin Song, Yun Zhao, Shi Jiao, Zhaocai Zhou. The Transitional Endoplasmic Reticulum ATPase p97 Regulates the Alternative Nuclear Factor NF-B Signaling via Partial Degradation of the NF-B Subunit p100. J Biol Chem, 2015, 290: 19558-68
  9. Zhubing Shi, Shi Jiao and Zhaocai Zhou. Structural dissection of Hippo signaling. Acta Biochim Biophys Sin (Shanghai), 2015, 47: 29-38 (Review)
  10. Shi Jiao, Huizhen Wang, Zhubing Shi, Aimei Dong, Wenjing Zhang, Xiaomin Song, Feng He, Yicui Wang, Zhenzhen Zhang, Wenjia Wang, Xin Wang, Tong Guo, Peixue Li, Yun Zhao, Hongbin Ji, Lei Zhang, Zhaocai Zhou. Gastric Cancer Therapy by a Peptide Mimicking VGLL4 Function as a YAP Antagonist. Cancer Cell, 2014, 25: 166-180 (Highlighted by Nature China)
  11. Wenjing Zhang, Yijun Gao, Peixue Li, Zhubing Shi, Tong Guo, Fei Li, Xiangkun Han, Yan Feng, Chao Zheng, Zuoyun Wang, Fuming Li, Haiquan Chen, Zhaocai Zhou*, Lei Zhang*, Hongbin Ji*. VGLL4 functions as a new tumor suppressor in lung cancer by negatively regulating the YAP-TEAD transcriptional complex. Cell Res, 2014, 24: 331-343.
  12. Chuanchuan Li, Miao Feng, Zhubing Shi, Qian Hao, Xiaomin Song, Wenjia Wang, Yun Zhao, Shi Jiao, Zhaocai Zhou. Structural and Biochemical Insights into the Activation Mechanisms of Germinal Center Kinase OSR1. J Biol Chem, 2014, 289: 35969-35978.
  13. Cuicui Chen, Zhubing Shi, Wenqing Zhang, Min Chen, Feng He, Zhenzhen Zhang, Yicui Wang, Miao Feng, Wenjia Wang, Yun Zhao, Jerry H. Brown, Shi Jiao, Zhaocai Zhou. Striatins Contain a Noncanonical Coiled Coil That Binds PP2A A to Form a 2:2 Heterotetrameric Core of Striatin-interacting Phosphatase and Kinase (STRIPAK) Complex. J Biol Chem, 2014, 289: 9651-9661.
  14. Qian Hao, Miao Feng, Zhubing Shi, Chuanchuan Li, Min Chen, Wenjia Wang, Meng Zhang, Shi Jiao, Zhaocai Zhou. Structural insights into regulatory mechanisms of MO25-mediated kinase activation. J Struct Biol, 2014, 186: 224-233
  15. Guoguang Liu, Zhubing Shi, Shi Jiao, Zhenzhen Zhang, Wenjia Wang, Cuicui Chen, Qiao Hao, Meng Zhang, Miao Feng, Liang Xu, Zhen Zhang, Zhaocai Zhou*, Min Zhang*. Structure of MST2 SARAH domain provides insights into its interaction with RAPL. J Struct Biol, 2014, 185: 366-374
  16. Feifei Mao, Xiaofeng Yang, Lin Fu, Xiangdong Lv, Zhao Zhang, Wenqing Wu, Siqi Yang, Zhaocai Zhou, Lei Zhang, Yun Zhao. The Kto-Skd Complex Can Regulate ptc Expression by Interacting with Cubitus interruptus (Ci) in the Hedgehog Signaling Pathway. J Biol Chem, 2014, 289: 22333-22341
  17. Yan Xiao, Yasuhiro Nagai, Guoping Deng, Takuya Ohtani, Zhiqiang Zhu, Zhaocai Zhou, Hongtao Zhang, Mei Q. Ji, John W. Lough, Arabinda Samanta, Wayne W. Hancock, Mark I. Greene. Dynamic interactions between TIP60 and p300 regulate FOXP3 function through a structural switch defined by a single lysine on TIP60. Cell Rep, 2014, 7: 1471-1480
  18. Meng Zhang, Liang Dong, Zhubing Shi, Shi Jiao, Zhen Zhang, Wenqing Zhang, Guoguang Liu, Cuicui Chen, Miao Feng, Qiao Hao, Wenjia Wang, Mengxin Yin, Yun Zhao, Lei Zhang, Zhaocai Zhou. Structural mechanism of CCM3 heterodimerization with GCKIII kinases. Structure (cell press), 2013, 21: 680-688
  19. Zhubing Shi, Shi Jiao, Zhen Zhang, Miao Ma, Zhao Zhang, Cuicui Chen, Ke Wang, Huizhen Wang, Lei Zhang, Yun Zhao, Zhaocai Zhou. Structure of the MST4 in complex with MO25 provides insights into its activation mechanism. Structure (cell press), 2013, 21: 449-561
  20. Miao Feng, Zhanyu Ding, Liang Xu, Liangliang Kong, Wenjia Wang, Shi Jiao, Zhubing Shi, Mark Greene, Yao Cong, Zhaocai Zhou. Structural and biochemical studies of RIG-I antiviral signaling. Protein Cell, 2013, 4: 142-154
  21. Zhao Zhang, Jing Feng, Chenyu Pan, Xiangdong Lv, Wenqing Wu, Zhaocai Zhou, Feng Liu, Lei Zhang, and Yun Zhao. Atrophin-Rpd3 complex represses Hedgehog signaling by acting as a corepressor of CiR. J Cell Biol, 2013, 203: 575-583
  22. Dawei Shi, Xiangdong Lv, Zhao Zhang, Xiaofeng Yang, Zhaocai Zhou, Lei Zhang, Yun Zhao. Smoothened Oligomerization/Higher Order Clustering in Lipid Rafts Is Essential for High Hedgehog Activity Transduction. J Biol Chem, 2013, 288: 12605-12614
  23. Tong Guo, Yi Lu, Peixue Li, Mengxin Yin, Dekang Lv, Wenjing Zhang, Huizhen Wang, Zhaocai Zhou, Hongbin Ji, Yun Zhao and Lei Zhang. A novel partner of Scalloped regulates Hippo signaling via antagonizing Scalloped-Yorkie activity. Cell Res, 2013, 23: 1201-1214
  24. Hongling Huang, Shimin Wang, Mengxin Yin, Liang Dong, Chao Wang, Wei Wu, Yi Lu, Miao Feng, Chuanyang Dai, Xiaocan Guo, Li Li, Bin Zhao, Zhaocai Zhou, Hongbin Ji, Jin Jiang, Yun Zhao, Xinyuan Liu, Lei Zhang. Par-1 Regulates Tissue Growth by Influencing Hippo Phosphorylation Status and Hippo-Salvador Association. PLoS Biol, 2013, 11: e1001620
  25. Xiaofeng Yang, Feifei Mao, Xiangdong Lv, Zhao Zhang, Lin Fu, Yi Lu, Wenqing Wu, Zhaocai Zhou, Lei Zhang, Yun Zhao. Drosophila Vps36 regulates Smo trafficking in Hedgehog signaling. J Cell Sci, 2013, 126: 4230-4238
  26. Bo Li, Congcong Wang, Zhaocai Zhou, Jian Zhao, Gang Pei. -Arrestin-1 directly interacts with Gs and regulates its function. FEBS Lett, 2013, 587: 410-416
  27. Wenjia Wang, Zhubing Shi, Shi Jiao, Cuicui Chen, Huizhen Wang, Guoguang Liu, Qiang Wang, Yun Zhao, Mark I. Greene, Zhaocai Zhou. Structural insights into SUN-KASH complexes across the nuclear envelope. Cell Res, 2012, 22: 1440-1452 (Cover story; Highlighted by A-IMBN)
  28. Xiaomin Song, Bin Li, Yan Xiao, Chunxia Chen, Qiang Wang, Yujie Liu, Alan Berezov, Chen Xu, Yayi Gao, Shiaw-Lin Wu, Hongtao Zhang, Barry Karger, Wayne Hancock, Andrew Wells, Zhaocai Zhou*, Mark Greene*. Structural and biological features of FOXP3 dimerization relevant to regulatory T cell function. Cell Rep, 2012, 1: 665-675
  29. Hailei Yin, Zhubing Shi, Shi Jiao, Cuicui Chen, Mark I. Greene, and Zhaocai Zhou. Germinal Center Kinases in Immune Regulation. Cell Mol Immunol, 2012, 9: 439-445 (Review)
  30. Yunyun Jin, Liang Dong, Yi Lu, Wenqing Wu, Qian Hao, Zhaocai Zhou, Jin Jiang, Yun Zhao, and Lei Zhang. Dimerization and cytoplasmic localization regulate hippo kinase signaling activity in organ size control. J Biol Chem, 2012, 287: 5784-5796
  31. Zhaocai Zhou, Xiulian Du, Zheng Cai, Xiaomin Song, Hongtao Zhang, Takako Mizuno, Emi Suzuki, Marla Rosanne Yee, Alan Berezov, Ramachandran Murali, Shiaw-Lin Wu, Barry L. Karger, Mark I. Greene, and Qiang Wang. Structure of the SUN domain defines features of a molecular bridge in the nuclear envelope. J Biol Chem, 2012, 287: 5317-5326
  32. Guoping Deng, Yan Xiao, Zhaocai Zhou, Yasuhiro Nagai, Hongtao Zhang, Bin Li, Mark I. Greene. Molecular and biological role of the FOXP3 N-terminal domain in immune regulation by T regulatory/suppressor cells. Exp Mol Pathol, 2012, 93: 334-338 (Review)
  33. E. Aaron Runkle, Hongtao Zhang, Zheng Cai, Zhiqiang Zhu, Barry L. Karger, Shiaw-Lin Wu, Donald M. ORourke, Zhaocai Zhou, Qiang Wang, Mark I. Greene. Reversion of the ErbB malignant phenotype and the DNA damage response. Exp Mol Pathol, 2012, 93: 324-333 (Review)
  34. Xiaomin Song, Min Zhang, Zhaocai Zhou*, Weimin Gong*. Ultra-high resolution crystal structure of a dimeric defensin SPE10. FEBS Lett, 2011, 585: 300-306
  35. Yan Xiao, Bin Li, Zhaocai Zhou, Wayne W Hancock, Hongtao Zhang, Mark I Greene. Histone acetyltransferase mediated regulation of FOXP3 acetylation and Treg function. Curr Opin Immunol, 2010, 22: 583-591 (Review)
  36. Zhaocai Zhou, Xiaomin Song, Alan Berezov, Bin Li, Mark I. Greene. Structural aspects of the FOXP3 regulatory complex as an immunopharmacological target. Int Immunopharmacol, 2009, 9: 518-20 (Review)
  37. Zhaocai Zhou, Xiaomin Song, Bin Li, Mark I. Greene. FOXP3 and its partners: structural and biochemical insights into the regulation of FOXP3 activity. Immunol Res, 2008, 42: 19-28 (Review)
  38. Zhaocai Zhou, Xiaomin Song, Alan Berezov, Geng Zhang, Yanjing Li, Hongtao Zhang, Ramachandran Murali, Bin Li, and Mark I. Greene. Human glucocorticoid induced TNF receptor ligand regulates its signaling activity through multiple oligomerization states. Proc Natl Acad Sci, 2008, 105: 5465-5470
  39. Zhaocai Zhou, Yukiko Tone, Xiaomin Song, Keiji Furuuchi, James D. Lear, Herman Waldmann, Masahide Tone, Mark I. Greene and Ramachandran Murali. Structural basis for dimeric ligand mediated mouse GITR activation. Proc Natl Acad Sci, 2008, 105: 641-645
  40. Zheng Cai, Geng zhang, Zhaocai Zhou, Kathryn Bembas, Jeffrey A. Drebin, Mark I. Greene, and Hongtao Zhang. Differential binding patterns of monoclonal antibody 2C4 to the ErbB3-p185Her2/neu and the EGFR- p185Her2/neu complexes. Oncogene, 2008, 27: 3870-3874
  41. Jerry H. Brown#, Zhaocai Zhou#, Ludmilla Reshetnikova, Howard Robinson, Rama Yammani, Larry S. Tobacman, and Carolyn Cohen. Structure of tropomyosins mid-region: bending and binding sites for actin. Proc Natl Acad Sci, 2005, 102: 18878-18883 (#equal contribution)
  42. Shujun Li, Zhaocai Zhou, Wangsheng Chu, Weimin Gong, Maurizio Benfatto, Tiandou Hu, Yaning Xie, Dingchang Xian, Ziyu Wu. Investigation of zinc-containing peptide deformylase from Leptospira interrogans by X-ray absorption near-edge spectroscopy. J Synchrotron Radiat, 2005, 12: 111-114
  43. Zhaocai Zhou, Xiaomin Song, and Weimin Gong. Novel conformational states of peptide deformylase from pathogenic bacterium Leptospira interrogans: implications for population shift. J Biol Chem, 2005, 280: 42391-42396
  44. Xiaomin Song, Zhaocai Zhou, Jing Wang, Fang Wu, Weimin Gong. Purification, characterization and preliminary crystallographic studies of a novel plant defensin from Pachyrrhizus erosus seeds. Acta Crystallogr D Biol Crystallogr, 2004, 60:1121-1124
  45. Shaojie Chang, Xiaomin Song, Ming Yan, Zhaocai Zhou, Fang Wu, Weimin Gong. Purification, characterization and preliminary crystallographic studies of a cysteine protease from Pachyrrhizus erosus seeds. Acta Crystallogr D Biol Crystallogr, 2004, 60: 187-189
  46. Lin Liu, Yanli Wang, Ping Zhang, Zhongjun Cheng, Mao Wan, Zhaocai Zhou, Weimin Gong. Expression, purification and preliminary crystallographic studies of human coactosin-like protein. Acta Crystallogr D Biol Crystallogr, 2004, 60: 1651-1653
  47. Zhiyi Wei, Ping Zhang, Zhaocai Zhou, Zhongjun Cheng, Mao Wan, Weimin Gong. Crystal structure of human eIF3k, the first structure of eIF3 subunits. J Biol Chem, 2004, 279: 34983-34990
  48. Zhaocai Zhou and Weimin Gong. Co-crystallization of LiPDF with potent inhibitor and molecular replacement schemes with eight subunits in an asymmetric unit. Acta Crystallogr D Biol Crystallogr, 2004, 60: 137-139
  49. Zhaocai Zhou, Xiaomin Song, Yikun Li and Weimin Gong. Unique structural characteristics of peptide deformylase from pathogenic bacterium Leptospira interrogans. J Mol Biol, 2004, 339: 207-215
  50. Fang Wu, Ming Yan, Yikun Li, Shaojie Chang, Xiaomin Song, Zhaocai Zhou, Weimin Gong. cDNA cloning, expression, and mutagenesis of a PR-10 protein SPE-16 from the seeds of Pachyrrhizus erosus. Biochem Bioph Res Co, 2003, 312: 761-766
  51. Zhaocai Zhou, Hanjian Liu, Yikun Li, Weimin Gong. Purification, crystallization and preliminary crystallographic studies of a class II chitinase from kidney bean seeds. Protein Peptide Lett, 2002, 9: 265-268
  52. Fang Wu, Yikun Li, Shaojie Chang, Zhaocai Zhou, Fang Wang, Xiaomin Song, Yujuan Lin, Weimin Gong. Purification, characterization and preliminary crystallographic studies of a PR-10 protein from Pachyrrhizus erosus seeds. Acta Crystallogr D Biol Crystallogr, 2002, 58: 2165-2167

Research Team

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