程金科 教授
細(xì)胞信號與轉(zhuǎn)導(dǎo)研究組
電話：63846590-778026
郵箱：[email protected]
研究方向
類泛素修飾（SUMOylation）是近年發(fā)現(xiàn)的一種新的蛋白質(zhì)修飾形式。它參與了對許多細(xì)胞生命活動過程的調(diào)節(jié)，包括細(xì)胞周期、細(xì)胞分裂、DNA損傷修復(fù)、細(xì)胞內(nèi)分子轉(zhuǎn)運(yùn)、調(diào)節(jié)蛋白質(zhì)穩(wěn)定和基因的轉(zhuǎn)錄等等。SUMOylation是由活化酶(E1)、接合酶(E2)、和連接酶(E3)等三個酶相繼作用來完成的。同時它又是一個動態(tài)、可逆的過程，其去SUMO 修飾的過程(De-SUMOylation)則是由一SUMO特異性蛋白酶(SENP) 家族來完成。本研究室的研究興趣主要是蛋白質(zhì)SUMO修飾的生物學(xué)功能, 特別是由SENP介導(dǎo)的去SUMO修飾過程對細(xì)胞信號轉(zhuǎn)導(dǎo)的調(diào)控作用以及它們在衰老與疾病過程中的作用與意義。
主要研究方向有：
1. 蛋白質(zhì)SUMO修飾與線粒體代謝調(diào)控。研究線粒體蛋白的SUMO修飾對線粒體代謝活性的調(diào)控作用與機(jī)制以及對細(xì)胞功能的影響。
2. 蛋白質(zhì)SUMO修飾與免疫調(diào)控。研究蛋白質(zhì)SUMO修飾對免疫細(xì)胞活性的調(diào)控作用及機(jī)制以及在炎癥和免疫相關(guān)疾病中的意義。
3. 蛋白質(zhì)SUMO修飾與衰老。研究衰老過程中蛋白質(zhì)SUMO修飾的作用與機(jī)制，尤其聚焦于線粒體蛋白質(zhì)SUMO修飾對衰老及衰老相關(guān)疾病的調(diào)控作用與機(jī)制。
個人簡歷
程金科，上海交通大學(xué)醫(yī)學(xué)院特聘教授，博士生導(dǎo)師，上海市腫瘤微環(huán)境與炎癥重點(diǎn)實(shí)驗(yàn)室主任，國家重點(diǎn)研發(fā)計劃項(xiàng)目首席科學(xué)家。中國生物化學(xué)與分子生物學(xué)會醫(yī)學(xué)生物化學(xué)與分子生物學(xué)分會副主任委員，上海市生物化學(xué)與分子生物學(xué)學(xué)會理事長。主要從事蛋白質(zhì)的SUMO修飾的基礎(chǔ)與疾病方面的研究, 包括由SENP介導(dǎo)的去SUMO修飾過程和對細(xì)胞信號轉(zhuǎn)導(dǎo)的調(diào)控機(jī)制，以及它們在發(fā)育與疾病過程中的作用與意義。在Cell, Nature Communications, Molecular Cell, Cancer research, Cell Report, Oncogene等雜志發(fā)表研究論文50多篇。已獲得多項(xiàng)國家自然科學(xué)基金重點(diǎn)項(xiàng)目和上海市科委等基金資助。
教育經(jīng)歷：
1983年本科畢業(yè)于湖南農(nóng)業(yè)大學(xué)獸醫(yī)專業(yè)；
1989年獲中國農(nóng)業(yè)大學(xué)動物病理學(xué)專業(yè)碩士學(xué)位；
1997年獲中國醫(yī)學(xué)科學(xué)院/北京協(xié)和醫(yī)學(xué)院腫瘤研究所細(xì)胞生物學(xué)博士學(xué)位。
工作經(jīng)歷：
1998－2004年在美國The University of Texas-M D Anderson Cancer Center 從事博士后研究；
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年任上海交通大學(xué)醫(yī)學(xué)院研究員，細(xì)胞信號轉(zhuǎn)導(dǎo)研究室PI；
2009-2016年擔(dān)任基礎(chǔ)醫(yī)學(xué)院生物化學(xué)與分子細(xì)胞生物學(xué)系系主任；
2016-2023年擔(dān)任上海交通大學(xué)醫(yī)學(xué)院基礎(chǔ)醫(yī)學(xué)院院長。
在研項(xiàng)目：
1.項(xiàng)目編號：82030075
項(xiàng)目名稱：SENP2整合FGF21和TGF-b信號調(diào)控乳腺癌細(xì)胞脂代謝并促進(jìn)EMT和腫瘤侵襲轉(zhuǎn)移的研究 。
負(fù)責(zé)人： 程金科
資助類別：國家自然科學(xué)基金重點(diǎn)項(xiàng)目
起止年限：2021.01.01-2025.12.31
資助金額：297萬元
2.項(xiàng)目編號：2020YFA0803600
項(xiàng)目名稱：組織器官代謝可塑性與記憶的調(diào)控機(jī)制及其生理病理意義
負(fù)責(zé)人：程金科（首席及課題三負(fù)責(zé)人）
資助類別：科技部國家重點(diǎn)研發(fā)計劃
起止年限：2020.12.01-2025.11.30
資助金額：2425萬元 （總項(xiàng)目），698萬元（課題三）
3.項(xiàng)目編號：82230049
項(xiàng)目名稱：SENP1-Sirt3軸調(diào)控線粒體代謝重編程及抗組織器官衰老的作用與機(jī)制研究。
負(fù)責(zé)人： 程金科
資助類別：國家自然科學(xué)基金重點(diǎn)項(xiàng)目
起止年限：2023.01.01-2027.12.31
資助金額：290萬元
論文與專著
第一作者和通訊作者文章：
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.
