师资队伍
程金科
  作者:  2018-12-31

基本信息 >>>

                                          
   程金科
   细胞信号与转导研究组
   电话:63846590-778026
   邮箱:jkcheng@shsmu.edu.cnjkcheng@shsmu.edu.cn

研究方向>>>

       类泛素修饰(SUMOylation)是近年发现的一种新的蛋白质修饰形式。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。SUMOylation是由活化酶(E1)、接合酶(E2)、和连接酶(E3)等三个酶相继作用来完成的。同时它又是一个动态、可逆的过程,其去SUMO 修饰的过程(De-SUMOylation)则是由一SUMO特异性蛋白酶(SENP) 家族来完成。本研究室的研究兴趣主要是蛋白质的SUMO修饰, 特别是由SENP介导的去SUMO修饰过程和对细胞信号转导的调控机制,以及它们在发育与疾病过程中的作用与意义。主要研究方向有:

1.蛋白质SUMO修饰与线粒体代谢调控。研究线粒体蛋白的SUMO修饰对线粒体代谢活性的调控作用与机制以及对细胞功能的影响。

2. 蛋白质SUMO修饰与肿瘤代谢及炎症反应调控。研究蛋白质SUMO修饰对肿瘤代谢及炎症细胞活性的调控作用以及在炎症相关疾病中的意义。

3. 蛋白质SUMO修饰与衰老机制研究。研究SENP1-Sirt3轴在人生理与病理过程中的作用与意义。       

个人简历 >>>

        程金科研究员,博士生导师。现任欧洲杯竞猜平台基础欧洲杯竞猜平台长,生物化学与分子细胞生物学系PI,欧洲杯竞猜平台特聘教授。主要从事蛋白质SUMO修饰与肿瘤、衰老及炎症研究;调控去SUMO化蛋白酶SENP的分子机制及生物学功能;蛋白质SUMO化修饰与代谢性疾病的研究。负责完成与正在主持的国家自然科学基金重点项目、国家自然科学面上基金、国家科技部重大研究计划等国家级项目14项;上海市优秀学科带头人、上海市浦江人才计划、上海市领军人才等市级项目12项。曾任中国细胞生物学会理事、中国生物化学与分子生物学会理事,目前担任上海市生物化学与分子生物学会理事长。先后以第一作者或通讯作者在Cell、Molecular Cell、Cancer Research、Oncogene等国际期刊上发表SCI论文30余篇,研究成果获上海市科学技术进步奖三等奖。

教育经历:

       1983年本科毕业于湖南农业大学兽医专业;

       1989年获中国农业大学动物病理学专业硕士学位;

       1997年获中国医学科学院/北京协和欧洲杯竞猜平台肿瘤研究所细胞生物学博士学位;

工作经历:

       19982004年在美国The University of Texas-M D Anderson Cancer Center 从事博士后研究;

       20042006年任The University of Texas-M D Anderson Cancer CenterInstructor

       20062007年任The University of Texas-M D Anderson Cancer CenterAssistant Professor

       2007年任欧洲杯竞猜平台研究员,细胞信号转导研究室PI

       2009-2016年担任基础欧洲杯竞猜平台生物化学与分子细胞生物学系系主任

       2017年担任欧洲杯竞猜平台基础欧洲杯竞猜平台院长。

科研项目 >>>

在研项目:


1. 项目编号:82030075

项目名称:SENP2整合FGF21TGF-b信号调控乳腺癌细胞脂代谢并促进EMT和肿瘤侵袭转移的研究  

负责人: 程金科

资助类别:国家自然科学基金重点项目

起止年限:2021.01.01-2025.12.31

资助金额:297万元


2. 项目编号:81730082

项目名称: SENP1-Sirt3轴调控免疫细胞代谢重编程及在抗肿瘤免疫中的作用与机制

负责人: 程金科

资助类别:国家自然科学基金重点项目

起止年限:2018.01.01-2022.12.31

资助金额:290万元


3. 项目编号:2020YFA0803600

项目名称:组织器官代谢可塑性与记忆的调控机制及其生理病理意义

负责人: 程金科 (首席及课题三负责人)

资助类别:科技部国家重点研发计划

起止年限:2020.12.01-2025.11.30      

资助金额:2425万元 (总项目),698万元(课题三)


4. 项目编号:2017-01-07 -00-01-E00050    

项目名称:蛋白质SUMO修饰对抗肿瘤免疫的调控作用及机制  

负责人: 程金科

资助类别:上海市教育委员会科研创新计划项目-重大项目  

起止年限:2017.06.30-2021.06.30

资助金额:300万元

论文与专著 >>>

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 Tranion 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 tranion 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 Tranion. 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 tranion 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,38191-201. 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. 28536682-36688. 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. 111118-1122 . 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)

40. Huang C, Cheng J, Bawa-Khalfe T, Yao X, Chin YE, Yeh ET. SUMOylated ORC2 Recruits a Histone Demethylase to Regulate Centromeric Histone Modification and Genomic Stability. Cell Rep. 15(1):147-57, 2016.

41. Xia N, Cai J, Wang F, Dong B, Liu S, Chen F, Cheng J, Zuo Y. SENP1 Is a Crucial Regulator for Cell Senescence through DeSUMOylation of Bmi1. Sci Rep. 2016 Sep 23; 6:34099. doi: 10.1038/srep34099

42. Dong B, Gao Y, Kang X, Gao H, Zhang J, Guo H, You MJ, Xue W, Cheng J, Huang Y. SENP1 promotes proliferation of clear cell renal cell carcinoma through activation of glycolysis. Oncotarget. 2016 7:80435-80449.

43. Bawa-Khalfe T, Yang FM, Ritho J, Lin HK, Cheng J, Yeh ET. SENP1 regulates PTEN stability to dictate prostate cancer development. Oncotarget. 2016 Nov 10. doi: 10.18632/oncotarget.13283. [Epub ahead of print]

44. Wang YP*, Zhou W, Wang J, Huang X, Zuo Y, Wang TS, Gao X, Xu YY, Zou SW, Liu YB, Cheng JK*, Lei QY*. Arginine Methylation of MDH1 by CARM1 Inhibits Glutamine Metabolism and Suppresses Pancreatic Cancer. Mol Cell. 2016 64:673-687 (* correspondence author).

45. Zhang H, Wang Y, Zhu A, Huang D, Deng S, Cheng J, Zhu MX, Li Y. SUMO-specific protease 1 protects neurons from apoptotic death during transient brain ischemia/reperfusion. Cell Death Dis. 2016 Nov 24;7(11):e2484.

46. Yu T, Zuo Y, Cai R, Huang X, Wu S, Zhang C, Chin YE, Li D, Zhang Z, Xia N, Wang Q, Shen H, Yao X, Zhang ZY, Xue S, Shen L, Cheng JK*. SENP1 regulates IFN-γ-STAT1 signaling through STAT3-SOCS3 negative feedback loop. Journal of Molecular Cell Biology , 2017, 9(2), 144–153.

47. Bo Wei, Chao Huang, Bin Liu, Yang Wang, Nansong Xia, Qiuju Fan, Guo-Qiang Chen, and Jinke Cheng*. Mitotic Phosphorylation of SENP3 Regulates DeSUMOylation of Chromosome-Associated Proteins and Chromosome Stability. Cancer Research.2018, 78(9):2171-2178.

48. Quan Zheng, Ying Cao, Yalan Chen, Jiqiu Wang, Qiuju Fan, Xian Huang, Yiping Wang, Tianshi Wang, Xiuzhi Wang, Jiao Ma, and Jinke Cheng*, Senp2 regulates adipose lipid storage by de-SUMOylation of Setdb1. Journal of Molecular Cell Biology. 2018, 10 (3):258-266.

49. Huang X, Zuo Y*, Wang, XZ, Wu, XF, Tan HS, Fan QJ, Dong BJ, Xue W, Chen GQ, Cheng JK*. SUMO-Specific Protease 1 Is Critical for Myeloid-Derived Suppressor Cell Development and Function. Cancer Research, 2019,79(15): 3891-3902.

50. Wang T, Cao Y, Zheng Q, Tu J, Zhou W, He J, Zhong J, Chen Y, Wang J, Cai R, Zuo Y, Wei B, Fan Q, Yang J, Wu Y, Yi J, Li D, Liu M, Wang C, Zhou A, Li Y, Wu X, Yang W, Chin YE, Chen G, Cheng JK*. SENP1-Sirt3 Signaling Controls Mitochondrial Protein Acetylation and Metabolism. Molecular Cell. 2019,75(4):823-834.

51. Liang QL; Zheng Q, Zuo Y,Chen YL, Ma J ,Ni PH*, Cheng JK*. SENP2 Suppresses Necdin Expression to Promote Brown Adipocyte Differentiation. Cell Reports, 2019, 28(8): 2004-2011.

52. Yang Wang ,Jing Tian, Chao Huang , Jiao Ma, Gaolei Hu, Yalan Chen, Tianshi Wang, Rong Cai,Yong Zuo, Hongsheng Tan, Qiuju Fan, Baijun Dong, Wei Xue, Jing Yi, Guoqiang Chen, Jun Tu and Jinke Cheng.P53 suppresses SENP3 phosphorylation to mediate G2 checkpoint.Cell Discovery ;( 2020) 6:21

53. Yun Yu , Yalan Chen , Kexin Liu, Jinke Cheng*, Jun Tu*. SUMOylation enhances the activity of IDH2 under oxidative stress. Biochemical and Biophysical Research Communications 532 (2020)591-597.

54.  Jianli He , Jinke Cheng ,and Tianshi Wang.SUMOylation-Mediated Response to Mitochondrial Stress.Int. J. Mol. Sci. 2020, 21, 5657; doi:10.3390/ijms21165657.

专利与技术许可 >>>

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