程金科 教授
细胞信号与转导研究组
电话：63846590-778026
邮箱：jkcheng@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、细胞内分子转运、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SUMO修饰的生物学功能, 特别是由SENP介导的去SUMO修饰过程对细胞信号转导的调控作用以及它们在衰老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修饰与免疫调控。研究蛋白质SUMO修饰对免疫细胞活性的调控作用及机制以及在炎症和免疫相关疾病中的意义。
3. 蛋白质SUMO修饰与衰老。研究衰老过程中蛋白质SUMO修饰的作用与机制，尤其聚焦于线粒体蛋白质SUMO修饰对衰老及衰老相关疾病的调控作用与机制。
个人简历
程金科，上海交通大学医学院特聘教授，博士生导师，上海市肿瘤微环境与炎症重点实验室主任，国家重点研发计划项目首席科学家。中国生物化学与分子生物学会医学生物化学与分子生物学分会副主任委员，上海市生物化学与分子生物学学会理事长。主要从事蛋白质的SUMO修饰的基础与疾病方面的研究, 包括由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。在Cell, Nature Communications, Molecular Cell, Cancer research, Cell Report, Oncogene等杂志发表研究论文50多篇。已获得多项国家自然科学基金重点项目和上海市科委等基金资助。
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/北京协和医学院肿瘤研究所细胞生物学博士学位。
工作经历：
1998－2004年在美国The University of Texas-M D Anderson Cancer Center 从事博士后研究；
2004－2006年任The University of Texas-M D Anderson Cancer Center，Instructor；
2006－2007年任The University of Texas-M D Anderson Cancer Center，Assistant Professor；
2007年任上海交通大学医学院研究员，细胞信号转导研究室PI；
2009-2016年担任基础医学院生物化学与分子细胞生物学系系主任；
2016-2023年担任上海交通大学医学院基础医学院院长。
在研项目：
1.项目编号：82030075
项目名称：SENP2整合FGF21和TGF-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：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）
3.项目编号：82230049
项目名称：SENP1-Sirt3轴调控线粒体代谢重编程及抗组织器官衰老的作用与机制研究。
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：2023.01.01-2027.12.31
资助金额：290万元
论文与专著
第一作者和通讯作者文章：
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、 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.
3、 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.
4、 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.
5、 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.
6、 Cheng J, Bawa T, Lee P, Gong L, Yeh ET. Role of desumoylation in the development of prostate cancer. Neoplasia, 8:667-676, 2006.
7、 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.
8、 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.
9、 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).
10、 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
11、 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.
12、 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.
13、 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.
14、 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.
15、 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.
16、 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.
17、 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.
18、 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.
19、 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.
20、 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， 35：4949-4956.(* correspondence author)
21、 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
22、 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.
23、 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).
24、 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.
25、 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.
26、 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.
27、 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.
28、 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.
29、 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.
30、 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
31、 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.
32、 Jianli He , Jinke Cheng and Tianshi Wang.SUMOylation-Mediated Response to Mitochondrial Stress.Int. J. Mol. Sci. 2020, 21, 5657; doi:10.3390/ijms21165657
33、 Xun Shangguan , Jianli He, Zehua Ma, Weiwei zhang , Yiyi Ji, Kai Shen, Zhiying Yue, Wenyu Li ,Zhixiang Xin, Quan Zheng, Ying Cao, Jiahua Pan, Baijun Dong, Jinke Cheng*, Qi Wang* &Wei Xue*，SUMOylation Controls the Binding of Hexokinase 2 to Mitochondria and Protects against Prostate Cancer Tumorigenesis.Nature Communications. 2021 Mar 22;12(1):1812.
34、 Jianli He#, Xun Shangguan# , Wei Zhou, Ying Cao, Quan Zheng, Jun Tu, Gaolei Hu, Zi Liang,Cen Jiang, Liufu Deng , Shengdian Wang, Wen Yang, Yong Zuo, Jiao Ma, Rong Cai, Yalan Chen,Qiuju Fan, Baijun Dong , Wei Xue, Hongsheng Tan, Yitao Qi, Jianmin Gu, Bing Su, Y. Eugene Chin,Guoqiang Chen , Qi Wang*, Tianshi Wang* & Jinke Cheng*. Glucose limitation activates AMPK coupled SENP1-Sirt3 signalling in mitochondria for T cell memory development. Nature Communications , (2021) 12:4371.
35、 Kan Yang* Yuhan Shi, Xiujuan Du, Jincheng Wang, Yuefang Zhang, Shifang Shan, Yiting Yuan,Ruoqing Wang, Chenhuan Zhou, Yuting Liu, Zilin Cai, Yanzhi Wang,Liu Fan, Huatai Xu, Juehua Yu,Jinke Cheng,* Fei Li,* and Zilong Qiu*.SENP1 in the retrosplenial agranular cortex regulates core autistic-like symptoms in mice. Cell Reports .37, 109939, November 2, 2021.
36、 Xiaoyu Song , Fengrui Yang, Xu Liu, Peng Xia , Wu Yin, Zhikai Wang, Yong Wang,Xiao Yuan, Zhen Dou, Kai Jiang, Mingming Ma, Bing Hu, Rui Zhang , Chao Xu ,Zhiyong Zhang , Ke Ruan, Ruijun Tian , Lin Li , Tao Liu, Donald L. Hill, Jianye Zang ,*Xing Liu* , Jinsong Li*, Jinke Cheng * and Xuebiao Yao *. Dynamic crotonylation of EB1 by TIP60 ensures accurate spindle positioning in mitosis. Nat Chem Biol. 2021 Dec;17(12):1314-1323.
37、 Hailong Zhang, Xian Zhao, Yanmin Guo, Ran Chen, Jianfeng He, Lian Li, Zhe Qiang, Qianqian Yang,Xiaojia Liu, Caihu Huang, Runhui Lu, Jiayu Fang, Yingting Cao1, Jiayi Huang, Yanli Wang, Jian Huang,Guo-Qiang Chen*, Jinke Cheng *& Jianxiu Yu*. Hypoxia regulates overall mRNA homeostasis by inducing Met1-linked linear ubiquitination of AGO2 in cancer cells. Nature Communications.(2021) 12:5416.
38、 Yajie Shen，Jingqi Zhou，KuiNie，Shuhua Cheng，Zhengming Chen，Wenhan Wang，Weiqing Wei，Daiji Jiang，Zijing Peng，Yizhuo Ren，Yirong Zhang，Qiuju Fan，Kristy L.Richards，Yitao Qi，Jinke Cheng*，Wayne Tam，Jiao Ma. (2021).Oncogenic role of SOX9-DHCR24-cholesterol biosynthesis axis in IGH-BCL2 positive diffuse large B-cell lymphomas.BLOOD. 2022,139(1):73-88.
39、 Wei Zhou,Gaolei Hu , Jianli He , Tianshi Wang , Yong Zuo , Ying Cao , Quan Zheng , Jun Tu , Jiao Ma , Rong Cai , Yalan Chen , Qiuju Fan , Baijun Dong , Hongsheng Tan , Qi Wang , Wei Xue* , Jinke Cheng *. SENP1-Sirt3 signaling promotes α-ketoglutarate production during M2 macrophage polarization. Cell Report.2022 Apr 12;39(2):110660.doi: 10.1016/j.celrep.2022.110660.
40、 Cen Jiang, Jianli He, Sunwang Xu*, Qi Wang,and Jinke Cheng*.NR4A1 promotes LEF1 expression in the pathogenesis of papillary thyroid cancer.Cell Death Discovery (2022) 8:46 , https://doi.org/10.1038/s41420-022-00843-7.
41、 Gaolei Hu, Yalan Chen, Xinyu Yang, Yang Wang, Jianli He, Tianshi Wang , Qiuju Fan, Liufu Deng, Jun Tu,Hongsheng Tan* and Jinke Cheng*.Mitotic SENP3 activation couples with cGAS signaling in tumor cells to stimulate anti-tumor immunity. Cell Death and Disease .2022.13:640.
42、 Yalan Chen,Kexin Liu,Geqiang Zhang,Jinke Cheng*,Jun Tu*.Monoclonal antibody-based systematic identification of SUMO1-modification sites reveals TFII‐I SUMOylation is involved in tumor growth.J Cell Physiol. 2023;1–13.DOI: 10.1002/jcp.31080.
