科学研究
蛋白质修饰与非编码RNA研究组
  作者:  2018-12-30

研究组长介绍 >>>

    余健秀, 男,博士,基础医学院特聘教授、博导。2000年获中山大学博士学位;2000-2002年任中山大学副教授;2002~2007年在美国Sanford-Burnham Medical Research Institute/UCSD从事博士后研究及任Staff Scientist;2008~2009年任美国纽约大学研究助理教授;2009年9月回国任上海交大医学院生物化学与分子细胞学系PI。主要致力于蛋白质修饰与非编码RNA在肿瘤发生发展中的作用机制研究。近年来在国际著名学术期刊Nat Chem Biol, Mol Cell, Nat Commun, EMBO  J,  Nucleic  Acids Res等发表研究论文50多篇,他用超 1700多次, 有3篇文章被Faculty 1000 推荐。主持国自然重点、重大研究计划、面上项目及科技部重大项目子项目等十多项课题,多次担任国自然基金医学部二审专家。

研究方向与进展 >>>

(1)探讨重要肿瘤抑制蛋白(如PTEN)的蛋白质修饰在肿瘤发生发展的作用及其分子机制。我们首次鉴定了 PTEN的SUMO化修饰,发现其直接介导 PTEN膜结合而抑制肿瘤发生发展,解析了 PTEN-PI3K-AKT通路的分子机制(Nat Commun 2012);

(2)蛋白质修饰调控非编码RNA生成和代谢的作用机制,系列研究揭示了由蛋白质修饰介导的非编码 RNA调控网络和作用机制。例如,首次发现 miRNA/siRNA作用效率受控于TARBP2的SUMO化修饰程度(Nat Commun 2015),Ago2的乙酰化修饰可以调控miRNA前体在miRISC复合物上的招募而改变特异miRNA的表达等;

(3)蛋白质修饰调控RNA的 m6A修饰。

科研项目 >>>

1) 81630075,国家自然科学基金重点项目 PTEN在DNA损伤修复中介导组蛋白H2A/H3修饰调控前列腺癌发生发展,2017.1-2021.12,275万元,主持人:余健秀  

2) 31671345,国家自然科学基金面上项目,Ago2乙酰化在miRNA途径中的功能与机制,2017.1-2020.12,65万元,主持人:余健秀

3) 81472571,国家自然科学基金面上项目,Shp2类泛素(SUMO)化修饰促进ERK信号通路激活而加速肝癌发生发展,2015.1-2018.12,74万元,主持人:余健秀

4) 81372190,国家自然科学基金面上项目,Grb2蛋白类泛素化修饰调节RPTPα--c-Src信号通路的研究,2014.1-2017.12,75万元,主持人:黄建

5) 81672709,国家自然科学基金面上项目,蛋白质酪氨酸磷酸酶RPTPα对新底物Ago2蛋白的去磷酸化调控研究,2017.1-2020.12,58万元,主持人:黄 建

6) 81572695,国家自然科学基金面上项目,EphB1促进肝癌发生发展的机制及其活性调控,2016.1-2019.12,57万元,主持人:陈勤

7) 81402326,国家自然科学基金青年项目, ARF 调控PTEN SUMOylation在非小细胞肺癌发生发展中的研究,2015.1-2017.12,23万元,主持人:金惠

8) 81602251,国家自然科学基金青年项目,lncRNA-UCA1在前列腺癌发生发展中的作用及其机制,2017.1-2019.12,17万元,主持人:王艳丽

9) 81702837,国家自然科学基金青年项目,Twist1蛋白SUMO修饰调控非小细胞肺癌耐药和转移的作用及机制,2018.01-2020.12,20万元,主持人:赵娴

10) 81702532,国家自然科学基金青年项目,前列腺癌中新型泛素水解酶调控PTEN蛋白稳定性的研究,2018.01-2020.12,20万元,主持人:邓蓉

11) 2016M600324,第60批中国博士后基金面上一等资助,Twist1类泛素化修饰在前列腺癌发生发展中的作用及机制,2016.07-2018.06,8万元,主持人:赵娴

12)2016M600323,第60批中国博士后基金面上一等资助, BAP1调控PTEN的泛素修饰在前列腺癌发生发展中的研究,2016.07-2018.06,8万元,主持人:邓蓉

代表性论文、专著与专利 >>>

1) Qin Chen*, Rong Deng, Xian Zhao, Haihua Yuan, Hailong Zhang, Jinzhuo Dou, Ran Chen, Hui Jin, Yanli Wang, Jian Huang, Jianxiu Yu*. SUMOylation of EphB1 suppresses neuroblastoma tumorigenesis via inhibiting PKCγ activation. Cellular Physiology and Biochemistry, 2017, in revision.

2) Yuzhang Du, Guofang Hou, Hailong Zhang, Jinzhuo Dou, Jianfeng He, Yanming Guo, Lian Li, Ran Chen, Yanli Wang, Rong Deng, Bin Jiang, Xian Zhao* and Jianxiu Yu*. SUMOylation of the m6A-RNA methyltransferase METTL3 modulates its function. Nucleic Acids Research, 2017, in Revision. 

3) Haihua Yuan, Rong Deng, Xian Zhao, Ran Chen, Guofang Hou, Hailong Zhang, Yanli Wang, Ming Xu, Bin Jiang*, Jianxiu Yu*. SUMO1 modification of KHSRP regulates tumorigenesis by preventing the TL-G-Rich miRNA biogenesis. Mol Cancer, 2017, Accepted.

4) Jing Wang, Rong Deng, Nan Cui, Hailong Zhang, Tianqi Liu, Jinzhuo Dou, Xian Zhao, Ran Chen, Yanli Wang, Jianxiu Yu*, Jian Huang*. Src SUMOylation inhibits tumor growth via decreasing FAK Y925 phosphorylation. Neoplasia, 2017, Accepted on Sep 1, 2017.

5) Jiang H, Deng R, Yang X, Shang J, Lu S, Zhao Y, Song K, Liu X, Zhang Q, Chen Y, Chinn YE, Wu G, Li J, Chen G, Yu J*, Zhang J*. Peptidomimetic inhibitors of APC-Asef interaction block colorectal cancer migration. Nat Chem Biol. 2017, 13(9): 994-1001. Cancer Discovery Research Watch:  http://cancerdiscovery.aacrjournals.org/content/early/2017/08/03/2159-8290.CD-RW2017-145.

6) Zhao X, Deng R, Wang Y, Zhang H, Dou J, Li L, Du Y, Chen R, Cheng J, Yu J*. Twist1/Dnmt3a and miR186 establish a regulatory circuit that controls inflammation-associated prostate cancer progression. Oncogenesis. 2017, 6(4): e315.

7) Zhu C, Chen C, Chen R, Deng R, Zhao X, Zhang H, Duo J, Chen Q, Jin H, Wang Y, Huang J, Xu M, Yu J*. K259-SUMOylation of DGCR8 promoted by p14ARF exerts a tumor-suppressive function. J Mol Cell Biol.  2016 Jul 19. pii: mjw030. 

8) Zhao X, Wang Y, Deng R, Zhang H, Dou J, Yuan H, Hou G, Du Y, Chen Q, Yu J*. miR186 suppresses prostate cancer progression by targeting Twist1. Oncotarget. 2016, 7(22): 33136-51.

9) Chen C, Zhu C, Huang J, Zhao X, Deng R, Zhang H, Dou J, Chen Q, Xu M, Yuan H, Wang Y, Yu J*. SUMOylation of TARBP2 regulates miRNA/siRNA efficiency. Nature Commun. 2015, 6:8899.

10) Lu S, Deng R, Jiang H, Song H, Li S, Shen Q, Huang W, Nussinov R, Yu J*, Zhang J*. The Mechanism of ATP-Dependent Allosteric Protection of Akt Kinase Phosphorylation. Structure. 2015, 23(9):1725-34.

11) Zhu C, Chen C, Huang J, Zhang H, Zhao X, Deng R, Dou J, Jin H, Chen R, Xu M, Chen Q, Wang Y, Yu J*. SUMOylation at K707 of DGCR8 controls direct function of primary microRNA. Nucleic Acids Res. 2015, 43(16):7945-60.

12) Chen Q, Zhao X, Zhang H, Yuan H, Zhu M, Sun Q, Lai X, Wang Y, Huang J, Yan J, Yu J*. MiR-130b suppresses prostate cancer metastasis through down-regulation of MMP2. Mol Carcinogen. 2015, 54(11):1292-300.

13) Lai  X, Chen Q, Zhu C, Deng R, Zhao X, Chen C, Wang Y. Yu J*, Huang J*. Regulation of RPTPα-c-Src signalling pathway by miR-218. FEBS J, 2015, 282(14):2722-34.

14) Deng R, Zhao X, Qu Y, Chen C, Zhu C, Zhang H, Yuan H, Jin H, Liu X, Wang Y, Chen Q, Huang J, Yu J*. Shp2 SUMOylation promotes ERK activation and hepatocellular carcinoma development. Oncotarget, 2015, 6(11):9355-69. 

15) Xu M, Zhu C, Zhao X, Chen C, Zhang H, Yuan H, Deng R, Dou J, Wang Y, Huang J, Chen Q, Jiang B, Yu J*Atypical ubiquitin E3 ligase complex Skp1-Pam-Fbxo45 controls the core epithelial-to-mesenchymal transition-inducing tranion factors. Oncotarget. 2015, 6(2): 979-94. 

16) Sun Q, Zhao X, Liu X, Wang Y, Huang J, Jiang B, Chen Q, Yu J*. miR-146a functions as a tumor suppressor in prostate cancer by targeting Rac1. Prostate. 2014, 74(16):1613-21. 

17) Zhu M, Chen Q, Liu X, Sun Q, Zhao X, Deng R, Wang Y, Huang J, Xu M, Yan J, Yu J*. lncRNA H19/miR-675 axis represses prostate cancer metastasis by targeting TGFBI. FEBS J. 2014, 281:3766-3775.

18) Qu Y, Chen Q, Lai X, Zhu C, Chen C, Zhao X, Deng R, Xu M, Yuan H, Wang Y, Yu J*, Huang J*. SUMOylation of Grb2 enhances the ERK activity by increasing its binding with Sos1. Mol Cancer, 2014, 13(1):95. 

19) Liu X, Chen Q, Yan J, Wang Y, Zhu C, Chen C, Zhao X, Xu M, Sun Q, Deng R, Zhang H, Qu Y, Huang J, Jiang B, Yu J*. MiRNA-296-3p-ICAM-1 axis promotes metastasis of prostate cancer by possible enhancing survival of natural killer cell-resistant circulating tumour cells. Cell Death Dis. 2013, 4:e928.

20) Yu J*, Deng R, Zhu HH, Zhang SS, Zhu C, Montminy M, Davis R, Feng GS*. Modulation of fatty acid synthase degradation by concerted action of p38 MAP kinase, E3 ligase COP1 and SH2-tyrosine phosphatase Shp2. J Biol Chem. 2013, 288(6):3823-30.

21) 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.  Nat Commun. 2012, 3:911. http://f1000.com/717847819 .

22) Liu X, Wang Y, Sun Q, Yan J, Huang J, Zhu S, Yu J*Identification of microRNA tranome involved in human natural killer cell activation. Immunol Lett. 2012, 143(2):208-17.

23) Yu J, Zhang D, Liu J, Li J, Yu Y, Wu XR, Huang C*. RhoGDI SUMOylation at Lys-138 Increases Its Binding Activity to Rho GTPase and its Inhibiting Cancer Cell Motility. J Biol Chem. 2012, 287(17):13752-60.

24) Yu J*, Zhang SS, Saito K, Williams S, Arimura Y, Ma Y, Ke Y, Baron V, Mercola D, Feng GS, Adamson E*, Mustelin T. PTEN regulation by Akt-EGR1-ARF-PTEN axis. EMBO J. 2009, 28(1):21-33.

25) Yu J, Baron V, Mercola D, Mustelin T, Adamson ED*. A network of p73, p53 and Egr1 is required for efficient apoptosis in tumor cells. Cell Death and Differentiation. 2007, 14(3):436-46.

26) Yu J, de Belle I, Liang H, Adamson ED*. Coactivating factors p300 and CBP are tranionally crossregulated by Egr1 in prostate cells, leading to divergent responses.  Mol Cell, 2004, 15(1): 83-94. http://www.f1000biology.com/article/id/1019957/evaluation

团队介绍 >>>

目前研究组共有14人,包括:

 

余健秀,PI,研究员/基础医学院特聘教授           jianxiu.yu@shsmu.edu.cn

 建,CO-PI,教授,《代谢生物化学》首席教师   jyhuanj@shsmu.edu.cn

王艳丽,实验师                                                                wangyl@shsmu.edu.cn

 冉,实验师                                                                  chenran@shsmu.edu.cn

 娴,博士后                                                               zhao20051050134@126.com

 蓉,博士后                                                                 dr_dengrong@163.com

张海龙,博士生                                                                zhanghailonghello@163.com

窦晋卓,博士生                                                                djz4420@163.com

侯国芳,博士生(联合培养)                                        monkeyhgf@163.com

何建锋,博士生                                                                910002@sjtu.edu.cn

郭岩珉,博士生                                                                gmy631@163.com

 莲,博士生                                                                  leelian@sjtu.edu.cn

 楠,硕士生                                                                  852189758@QQ.com

刘天齐,硕士生                                                                liutianqit@163.com