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机构概况

  

简 历

程金科, 博士，教授, 博士生导师

上海交通大学医学院医学科学研究院细胞信号转导研究室 主任

上海交通大学医学院生物化学与分子细胞生物学系 系主任

上海市肿瘤微环境与炎症重点实验室 主任

上海市重庆南路280号7号楼405室, 上海, 200025

Tel：021-64661525

Email：jkcheng@shsmu.edu.cn

教育经历

1979-1983  湖南农业大学畜牧兽医系，兽医专业  学士

1986-1989  中国农业大学动物医学院，动物病理学专业  硕士

1994-1997  中国协和医科大学，细胞生物学专业  博士

博士后经历

1998-2002  The University of Texas－M. D. Anderson Cancer Center Department of Immunology. 

2003-3004  The University of Texas－Health Science Center  Institute of Molecular Medicine.

主要学术任职

1990-1995  讲师, 北京农学院

1996-1998  副教授, 北京农学院

2004-2005  Instructor, The University of Texas - M.D.Anderson Cancer Center

2006-2007  Assistant Professor, The University of Texas - M. D. Anderson Cancer Center

2007-         教授, 上海交通大学医学院

    

专利与技术许可

 

     Screening for modulators of MEKK2 and MEKK3. WO/2005/056825, 23-06-2005.

 

其他学术任职

 

2006-2007    Western 5B Peer Review Committee of American Heart Association   

(美国心脏协会同行评审委员).

  2009-      上海交通大学医学院教授会委员

2009-      上海交通大学基础医学院教授会委员/主席

2008-      上海市肿瘤研究所，癌基因及相关基因国家重点实验室 研究员

2009-      上海市口腔医学重点实验室学术委员会委员

2008-      上海交通大学学报（医学版） 编委

2011-      中国细胞生物学学会 理事

2011-      上海市生物化学与分子生物学学会 理事/副秘书长/副理事长

2012-      上海市细胞生物学会  副理事长

2013-      中国生物化学与分子生物学学会 理事

2014-      Cell Division， Associate Editor

 

实验室主要研究方向

实验室的研究主要集中在蛋白质SUMO化修饰及介导的细胞信号通路在生理和病理过程中的作用与机制。蛋白质SUMO化修饰是近十年来发现的一种新的蛋白质翻译后修饰形式，它参与了对许多细胞生命活动过程的调节，包括细胞周期、细胞分裂、DNA损伤修复、细胞内转运、调节蛋白质稳定和基因的转录等等；并且还发现与许多疾病发生发展过程密切相关。应用基因敲除小鼠模型，我们主要研究特异性去SUMO化蛋白酶（SENP）的生物学功能及其作用的分子细胞基础。主要的研究方向有：

  1. SENP1与炎症。我们发现SENP1调控细胞缺氧信号通路与血管内皮细胞的成血管活性密切相关。进一步发现SENP1对以巨噬细胞为主的炎症反应中有重要的调控作用。SENP1通过调控T和B细胞的分化与巨噬细胞的活化等参与一些先天性免疫反应。我们将进一步研究SENP1对炎症反应的调控在肿瘤及代谢性疾病中的作用与机制。
  2. SENP1与代谢。我们发现SENP1对线粒体生成的调控作用，这一作用与细胞的能量代谢有关。已经证明SENP1对线粒体的调控作用参与了心脏功能失常的病理过程。我们将进一步研究SENP1对线粒体代谢的调控作用与一些代谢性疾病的关系。
  3. SENP2与脂肪细胞的分化。 SENP2基因敲除小鼠表现有脂肪组织形成的缺陷。我们将研究SENP2参与脂肪细胞的分化与脂肪组织的形成的作用与肥胖发生的关系。
  4. SENP3对细胞分裂的调控及中肿瘤中的作用。 我们发现SENP3调控细胞的分裂，并显示与肿瘤的发生相关。将进一步研究SENP3调控细胞分裂的机制及与肿瘤发生发展的关系。
 

 

发表论文、著作

 

  1. 代表性论文（2000-今）

 

  1. Cheng J, Yang J, Xia Y, Karin M, Su B. Syndergistic interaction of MEK kinase 2, c-Jun N-terminal kinase (JNK) kinase 2, and JNK1 results in efficient and specific JNK1 activation. Molecular and Cellular Biology , 20:2334-2342, 2000.
  2. Yang J, Lin Y, Guo Z, Cheng J, Huang H, Liao W, Chen J, Liu ZG, Su B. Essential role of MEKK3 in TNFa induced NF-kB activation. Nature Immunology , 2:620-624, 2001.
  3. Su B, Cheng J, Yang J, Guo Z. MEKK2 mediates T cell receptor signals in JNK activation and IL-2 gene expression. Journal of Biological Chemistry, 276:14784-14790, 2001.
  4. Guo Z, Clydesdale G, Cheng J, Kim K, Gan L, McConkey DJ, Ullrich SE, Zhuang Y, Su B.  Disruption of MEKK2 in mice reveals an unexpected role for MEKK2 in modulating T-cell receptor signal transduction. Molecular and Cellular Biology, 22:5761-5768, 2002.
  5. Huang Q, Yang J, Lin Y, Walker C, Cheng J, Liu ZG, Su B.  Differential regulation of interleukin 1 receptor and Toll-like receptor signaling by MEKK3. Nature Immunology, 5:98-103, 2004.
  6. Cheng J, Wang D, Wang Z, Yeh ETH. SENP1 Enhances Androgen Receptor-Dependent Transcription through Desumoylation of Histone Deacetylase 1. Molecular and Cellular Biology, 24:6021-6028, 2004.
  7. Kho Y, Kim SC, Jiang C, Barma D, Kwon SW, Cheng J, Jaunbergs J, Weinbaum C, Tamanoi F, Falck J, Zhao Y. A tagging-via-substrate technology for detection and proteomics of farnesylated proteins. PNAS, 101:12479-12484, 2004.
  8. Cheng J, Zhang D, Kim K, Zhao Y, Su B. Mip1, an MEKK2-interacting protein, controls MEKK2 dimerization and activation. Molecular and Cellular Biology, 25:5955-5964, 2005.
  9. Veltman IM, Vreede LA, Cheng J, Looijenga LH, Janssen B, Schoenmakers EF, Yeh ETH, van Kessel AG. Fusion of the SUMO/Sentrin-specific protease 1 gene SENP1 and the embryonic polarity-related mesoderm development gene MESDC2 in a patient with an infantile teratoma and a constitutional t(12;15)(q13;q25).  Human Molecular Genetics, 14:1955-1963, 2005.
  10. Cheng J, Pekins ND, Yeh ETH. Differential regulation of c-Jun-dependent transcription by SUMO-specific proteases.  Journal of Biological Chemistry, 280:14492-14498, 2005.
  11. Cheng J, Yu L, Zhang D, Huang Q, Spencer D, Su B. Dimerization through the catalytic domain is essential for MEKK2 activation.  Journal of Biological Chemistry, 280: 13477-13482, 2005.
  12.  Cheng J, Bawa T, Lee P, Gong L, Yeh ET. Role of desumoylation in the development of prostate cancer. Neoplasia, 8:667-676, 2006.
  13.  Gao F, Cheng J, Shi T, and Yeh ET. NEDDylation of a Breast Cancer–asociated Protein Recruits a Class III Histone Deacetylase that Represses NF-kB-dependent Transcription. Nature Cell Biology, 8:1171-1177, 2006.
  14. Cheng J, Kang X, Zhang S and Yeh ET. SUMO-specific protease 1 is essential for stabilization of HIF1a during hypoxia. Cell, 131:584-595, 2007.
  15. Bawa-Khalfe T, Cheng J, Wang Z and Yeh ET. Induction of the sumo-specific protease 1 transcription by the androgen receptor in prostate cancer cells. Journal of Biological Chemistry, 282:37341-37349, 2007.
  16. Huang C, Han Y, Wang Y, Sun X, Yan S, Yeh ET, Chen Y, Cang H, Li H, Shi G, Cheng J, Tang X, Yi J. SENP3 is responsible for HIF-1 transactivation under mild oxidative stress via p300 de-SUMOylation. EMBO J, 28:2748-62, 2009.
  17. Lu H, Liu B, You S, Xue Q, Zhang F, Cheng J, Yu B. The activity-dependent stimuli increase SUMO modification in SHSY5Y cells. Biochem Biophys Res Commun. 18;390:872-876. 2009.
  18. Kang X, Qi Y, Zuo Y, Wang Q, Zou Y, Schwartz RJ, Cheng J *, and Yeh ET*. SUMO-specific protease 2 is essential for suppression of polycomb group proteins mediated gene silencing during embryonic development, Molecular Cell,，38：191-201. 2010 (* correspondence author).
  19.  Bawa-Khalfe T, Cheng J, Lin SH, Ittmann MM, Yeh ET. SENP1 induces prostatic intraepithelial neoplasia through multiple mechanisms. J Biol Chem， 285(33):25859-66. 2010.
  20. Kang X, Li J, Zou Y, Yi J, Zhang H, Cao M, Yeh ET, Cheng J. PIASy stimulates HIF1α SUMOylation and negatively regulates HIF1α activity in response to hypoxia. Oncogene, 29:5568-5578. 2010
  21. Xu Y, Zuo Y, Zhang H, Kang X, Yue F, Yi Z, Liu M, Yeh ET, Chen G, Cheng J.  Induction of SENP1 in endothelial cells contributes to hypoxia-driven VEGF expression and angiogenesis. J Biol Chem. 285：36682-36688. 2010.
  22. Xu K, Klenk C, Liu B, Keiner B, Cheng J, Zheng BJ, Li L, Han Q, Wang C, Li T, Chen Z, Shu Y, Liu J, Klenk HD, Sun B. Modification of nonstructural protein 1 of influenza A virus by SUMO1. J Virol. 85:1086-1098. 2010.
  23. Ran Y, Liu TT, Zhou Q, Li S, Mao AP, Li Y, Liu LJ, Cheng JK, Shu HB. SENP2 negatively regulates cellular antiviral response by deSUMOylating IRF3 and conditioning it for ubiquitination and degradation. J Mol Cell Biol. 3:283-92. 2011.
  24. Nguyen TV, Angkasekwinai P,Dou H, Lin FM,Lu LS, Cheng J, Chin YE, Dong C, Yeh ET. SUMO-Specific Protease 1 Is Critical for Early Lymphoid Development through Regulation of STAT5 Activation. Molecular Cell. 45:210-221. 2012.
  25. Zhou J, Fan Q, Zhang Z, Zou Y, Cai R, Wang Q, Zuo Y, and Cheng J. SENP1 Deficiency Promotes ER Stress-Induced Apoptosis by Increasing XBP1 SUMOylation. Cell Cycle. 11：1118-1122 . 2012.
  26. Huang J, Yan J, Zhang J, Zhu S, Wang Y, Shi T, Zhu C, Chen C, Liu X, Cheng J, Mustelin T, Feng GS, Chen G, Yu J. SUMO1 modification of PTEN regulates tumorigenesis by controlling its association with the plasma membrane. Nature Commun. 3: 911. 2012.
  27. Cai R, Yu T, Huang C, Xia X, Liu X, Gu J, Xue S, Yeh ET, Cheng J. SUMO-specific protease 1 regulates mitochondrial biogenesis through PGC-1α. J Biol Chem. 287:44464-44470. 2012.
  28. Wang Q, Xia N, Li T, Xu Y, Zou Y, Zuo Y, Fan Q, Bawa-Khalfe T, Yeh ET, Cheng J. SUMO-specific protease 1 promotes prostate cancer progression and metastasis. Oncogene. 32:2493-2498. 2013.
  29. Tang S, Huang G, Tong X, Xu L, Cai R, Li J, Zhou X, Song S, Huang C, Cheng J. Role of SUMO-specific protease 2 in reprogramming cellular glucose metabolism. PLoS One. May 14;8(5):e63965. 2013.
  30. Qi Y, Zuo Y, Yeh ET, Cheng J. An essential role of SUMO-specific protease 2 in myostatin expression and myogenesis. J Biol Chem. 289:3288-3293. 2014. 
  31. Wang J, Liu X, Dou Z, Chen L, Jiang H, Fu C, Fu G, Liu D, Zhang J, Zhu T, Fang J, Zang J, Cheng J, Teng M, Ding X, Yao X. Mitotic regulator Mis18β interacts with and specifies the centromeric assembly of molecular chaperone holliday junction recognition protein (HJURP). J Biol Chem. 289:8326-36, 2014.
  32. Han Q, Chang C, Li L, Klenk C, Cheng J, Chen Y, Xia N, Shu Y, Chen Z, Gabriel G, Sun B, Xu K. Sumoylation of influenza A virus nucleoprotein is essential for intracellular trafficking and virus growth. J Virol. 88:9379-9390. 2014
  33. Liu B, Wang T, Mei W, Li D, Cai R, Zuo Y, Cheng J. SUMO-Specific Protease 1 De-SUMOylates Sharp-1 and Controls Adipocyte Differentiation. J Biol Chem. 289:22358-22364. 2014.
  34. Qi Y, Wang J, Bomben VC, Li DP, Chen SR, Sun H, Xi Y, Reed JG, Cheng J, Pan HL, Noebels JL, Yeh ET. Hyper-SUMOylation of the Kv7 potassium channel diminishes the M-current leading to seizures and sudden death. Neuron. 83:1159-1171. 2014.
  35. Gu J, Fan Y, Liu X, Zhou L, Cheng J, Cai R, Xue S. SENP1 protects against myocardial ischaemia/reperfusion injury via a HIF1α-dependent pathway. Cardiovasc Res. 104:83-92. 2014
  36. Xiao N, Li H, Mei W, Cheng J. SUMOylation Attenuates Human β-arrestin 2 Inhibition of IL-1R-TRAF6 Signaling. J Biol Chem. 290:1927-35. 2015.
  37. Sun H, Lu L, Zuo Y, Wang Y, Jiao Y, Zeng WZ, Huang C, Zhu MX, Zamponi GW, Zhou T, Xu TL, Cheng J, Li Y. Kainate receptor activation induces glycine receptor endocytosis through PKC deSUMOylation. Nat Commun. 2014 Sep 19;5:4980. doi: 10.1038/ncomms5980.
  38. Cai R, Gu J, Sun H, Liu X, Mei W, Qi Y, Xue S, Ren S, Rabinowitz JE, Wang Y, Yeh ET, Cheng J. Induction of SENP1 in myocardium contributes to abnormities of mitochondria and cardiomyopathy. J Mol Cell Cardiol. 79:115-122. 2015.
  39. Cai J, Zuo Y, Wang T, Cao Y, Cai R, Chen FL, Cheng J*, Mu J*. A crucial role of SUMOylation in modulating Sirt6 deacetylation of H3 at lysine 56 and its tumor suppressive activity. Oncogene. 2016 Feb 22. doi: 10.1038/onc.2016.24. [Epub ahead of print] (* correspondence author)
  1. 著作

1．Su B, Guo Z, Cheng J, Karin M.  Mitogen-activated protein kinase cascades and regulation of gene expression. Stem Cells and Developmental Biology Military Medical Science Press. P:51-58, 2000.

2． Zhang S, Cheng J, Yeh ETH. Ubiquitination, Sumoylation and De-Sumoylation of HIF-1α, a key molecule involved in brain development and adaptation to hypoxia in adult brain. In: The ubiquitin proteasome system in the central nervous system: from physiology to pathology-2008 Update. Ed(s) Di Napoli M, Wojcik C. Nova Science Publishers Inc: New York, 441-468, 2010.

 

主要课题支持

 

1．973项目“蛋白质翻译后修饰的发生与调控机制及其生理病理效应”， 子课题3 “蛋白质修饰在癌症和糖尿病发病中的作用研究” 2009CB918403， 骨干， 2009-2013， 200万。

2．973项目“细胞生长调控的重要蛋白质群的功能与作用机制”，子课题4 “细胞周期中蛋白质修饰的作用与调控机制”， 2010CB912104， 组长，2010-2014， 248 万。

3．国家自然科学基金，重大研究计划（重点支持），SUMO 特异性蛋白酶2 在心脏发育中的作用与调控机制，91019021， 主持人，2011-2014， 200万。

4．国家自然科学基金，重大研究计划（重点支持），SUMO 特异性蛋白酶1 在肿瘤炎症反应中的调节作用及分子基础，91229202， 主持人，2013-2016， 300万.

5．国家自然科学基金，重点项目，SUMO特异性蛋白酶3调控细胞分裂的作用及与肿瘤发生的关系，81430069， 主持人，2015-2019， 320万.
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