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科學(xué)研究
蛋白質(zhì)修飾與非編碼RNA研究組
  作者:  2018-12-30

研究組長介紹 >>>

    余健秀, 男,博士,,基礎(chǔ)醫(yī)學(xué)院特聘教授,、博導(dǎo)。2000年獲中山大學(xué)博士學(xué)位,;2000-2002年任中山大學(xué)副教授,;2002~2007年在美國Sanford-Burnham Medical Research Institute/UCSD從事博士后研究及任Staff Scientist;2008~2009年任美國紐約大學(xué)研究助理教授,;2009年9月回國任上海交大醫(yī)學(xué)院生物化學(xué)與分子細(xì)胞學(xué)系PI,。主要致力于蛋白質(zhì)修飾與非編碼RNA在腫瘤發(fā)生發(fā)展中的作用機制研究。近年來在國際著名學(xué)術(shù)期刊Nat Chem Biol, Mol Cell, Nat Commun, EMBO  J,  Nucleic  Acids Res等發(fā)表研究論文50多篇,,他用超 1700多次, 有3篇文章被Faculty 1000 推薦,。主持國自然重點、重大研究計劃,、面上項目及科技部重大項目子項目等十多項課題,,多次擔(dān)任國自然基金醫(yī)學(xué)部二審專家。

研究方向與進(jìn)展 >>>

(1)探討重要腫瘤抑制蛋白(如PTEN)的蛋白質(zhì)修飾在腫瘤發(fā)生發(fā)展的作用及其分子機制,。我們首次鑒定了 PTEN的SUMO化修飾,,發(fā)現(xiàn)其直接介導(dǎo) PTEN膜結(jié)合而抑制腫瘤發(fā)生發(fā)展,解析了 PTEN-PI3K-AKT通路的分子機制(Nat Commun 2012),;

(2)蛋白質(zhì)修飾調(diào)控非編碼RNA生成和代謝的作用機制,,系列研究揭示了由蛋白質(zhì)修飾介導(dǎo)的非編碼 RNA調(diào)控網(wǎng)絡(luò)和作用機制。例如,,首次發(fā)現(xiàn) miRNA/siRNA作用效率受控于TARBP2的SUMO化修飾程度(Nat Commun 2015),,Ago2的乙酰化修飾可以調(diào)控miRNA前體在miRISC復(fù)合物上的招募而改變特異miRNA的表達(dá)等,;

(3)蛋白質(zhì)修飾調(diào)控RNA的 m6A修飾,。

科研項目 >>>

1) 81630075,國家自然科學(xué)基金重點項目 PTEN在DNA損傷修復(fù)中介導(dǎo)組蛋白H2A/H3修飾調(diào)控前列腺癌發(fā)生發(fā)展,,2017.1-2021.12,,275萬元,主持人:余健秀  

2) 31671345,,國家自然科學(xué)基金面上項目,,Ago2乙酰化在miRNA途徑中的功能與機制,,2017.1-2020.12,,65萬元,,主持人:余健秀

3) 81472571,國家自然科學(xué)基金面上項目,,Shp2類泛素(SUMO)化修飾促進(jìn)ERK信號通路激活而加速肝癌發(fā)生發(fā)展,,2015.1-2018.12,74萬元,,主持人:余健秀

4) 81372190,,國家自然科學(xué)基金面上項目,Grb2蛋白類泛素化修飾調(diào)節(jié)RPTPα--c-Src信號通路的研究,,2014.1-2017.12,,75萬元,主持人:黃建

5) 81672709,,國家自然科學(xué)基金面上項目,,蛋白質(zhì)酪氨酸磷酸酶RPTPα對新底物Ago2蛋白的去磷酸化調(diào)控研究,2017.1-2020.12,,58萬元,,主持人:黃 建

6) 81572695,國家自然科學(xué)基金面上項目,,EphB1促進(jìn)肝癌發(fā)生發(fā)展的機制及其活性調(diào)控,2016.1-2019.12,,57萬元,,主持人:陳勤

7) 81402326,國家自然科學(xué)基金青年項目,, ARF 調(diào)控PTEN SUMOylation在非小細(xì)胞肺癌發(fā)生發(fā)展中的研究,,2015.1-2017.12,23萬元,,主持人:金惠

8) 81602251,,國家自然科學(xué)基金青年項目,lncRNA-UCA1在前列腺癌發(fā)生發(fā)展中的作用及其機制,,2017.1-2019.12,,17萬元,主持人:王艷麗

9) 81702837,,國家自然科學(xué)基金青年項目,,Twist1蛋白SUMO修飾調(diào)控非小細(xì)胞肺癌耐藥和轉(zhuǎn)移的作用及機制,2018.01-2020.12,,20萬元,,主持人:趙嫻

10) 81702532,國家自然科學(xué)基金青年項目,,前列腺癌中新型泛素水解酶調(diào)控PTEN蛋白穩(wěn)定性的研究,,2018.01-2020.12,,20萬元,主持人:鄧蓉

11) 2016M600324,,第60批中國博士后基金面上一等資助,,Twist1類泛素化修飾在前列腺癌發(fā)生發(fā)展中的作用及機制,2016.07-2018.06,,8萬元,,主持人:趙嫻

12)2016M600323,第60批中國博士后基金面上一等資助,, BAP1調(diào)控PTEN的泛素修飾在前列腺癌發(fā)生發(fā)展中的研究,,2016.07-2018.06,8萬元,,主持人:鄧蓉

代表性論文,、專著與專利 >>>

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

團隊介紹 >>>

目前研究組共有14人,包括:

 

余健秀,,PI,,研究員/基礎(chǔ)醫(yī)學(xué)院特聘教授           [email protected]

 建,CO-PI,,教授,,《代謝生物化學(xué)》首席教師   [email protected]

王艷麗,實驗師                                                                [email protected]

 冉,,實驗師                                                                  [email protected]

 嫻,,博士后                                                               [email protected]

 蓉,博士后                                                                 [email protected]

張海龍,,博士生                                                                [email protected]

竇晉卓,,博士生                                                                [email protected]

侯國芳,博士生(聯(lián)合培養(yǎng))                                        [email protected]

何建鋒,,博士生                                                                [email protected]

郭巖珉,,博士生                                                                [email protected]

 蓮,博士生                                                                  [email protected]

 楠,,碩士生                                                                  [email protected]

劉天齊,,碩士生                                                                [email protected]