购宝钱包

Proteomics Center

She Chen, Ph.D.

Associate Investigator and Director of Proteomics Center, NIBS,Beijing, China

Tel： 010-80726688-8370

E-mail: chenshe@qfwhyh.com

中心主任介绍：

陈涉研究员1995年于武汉大学取得生物化学学士学位；

1998年于中国科研实验室生物物理购宝钱包 取得生物物理硕士学位；

2000年于美国Iowa State University取得食品科学硕士学位；

2009年于北京师范大学取得生物化学及分子生物学博士学位。

2001年至2004年间分别于美国University of Texas Southwestern Medical Center at Dallas和美国MDS Proteomics Inc.公司从事蛋白质生物质谱技术工作。

2004年回国建立北京科学生命购宝钱包 蛋白质组中心，现任北京科学生命购宝钱包 高级研究员，博士生导师，蛋白组中心主任。

陈涉研究员在过去十年间致力于蛋白质生物质谱技术的开发和应用，将生物质谱技术运用到包括病原体和宿主的相互作用、真核生物细胞表观遗传学信息的传递、昼夜节律的调控、程序性细胞死亡、细胞自吞噬、RNAi等众多基础生物学领域，取得了一系列重要成果，在包括Nature, Science, 购宝钱包 在内的高水平国际期刊上发表研究论文60余篇。

北京科学生命购宝钱包 蛋白质组中心简介:

北京科学生命购宝钱包 蛋白质组中心筹建于2004年，中心的核心组成部分为生物质谱实验室，拥有LTQ Orbitrap Velos、Q Exactive等多台大型生物质谱仪，为购宝钱包 各实验室给予高质量的生物质谱分析服务。服务内容包括蛋白质和多肽分子量测定，蛋白质的鉴定，蛋白质翻译后修饰的分析与鉴定，复杂蛋白质混合样品的分析，以及蛋白质组的比较定量研究。

中心在持续开发和完善各种先进的生物质谱分析技术的基础上，致力于将这些技术有效的运用到基础生物学研究中去，帮助解决基础生物学研究领域中的各个重大生物学问题。中心广泛召开合作研究，根据各个具体生物学问题的需要开发和完善相应的生物质谱技术，加快这些生物学问题的解决，促进基础生物学研究领域的开展。

联系方式：

北京科学生命购宝钱包 蛋白质组中心

电话：010-80726688转8372

传真：010-80727513

地址：北京市昌平区中关村科学生命园科学园路七号

邮编：102206

所内人员请于蛋白质组中心主页下载质谱分析送样表：质谱分析送样表

部分发表文章:

1.    Li, S., Zhang, L., Yao, Q., Li, L., Dong, N., Rong, J., Gao, W., Ding, X., Sun, L., Chen, X.,Chen, S.#, and Shao, F.#(2013). Pathogen blocks host death receptor signalling by arginine GlcNAcylation of death domains.Nature501(7466): 242-246.(#共同通讯作者).

2.    Sun, L., Wang, H., Wang, Z., He, S.,Chen, S., Liao, D., Wang, L., Yan, J., Liu, W., Lei, X., and Wang, X. (2012). Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 Kinase.购宝钱包 148(1-2): 213-227

3.    Xu, M., Wang, W.,Chen, S.#, and Zhu, B.#(2012). A model for mitotic inheritance of histone lysine methylation.EMBO reports13(1): 60-67.(#共同通讯作者).

4.    Xu, M.,Chen, S.#, and Zhu, B.#(2012). Investigating the 购宝钱包 cycle-associated dynamics of histone modifications using quantitative mass spectrometry.Methods Enzymol.512: 29-55.(#共同通讯作者).

5.    Zhang, L., Ding, X., Cui, J., Xu, H., Chen, J., Gong, Y. N., Hu, L., Zhou, Y., Ge, J., Lu, Q., Liu, L.,Chen, S., and Shao, F. (2011). Cysteine methylation disrupts ubiquitin-chain sensing in NF-kappaB activation.Nature481(7380): 204-208

6.    Shang, L.,Chen, S., Du, F., Li, S., Zhao, L., and Wang, X. (2011). Nutrient starvation elicits an acute autophagic response mediated by Ulk1 dephosphorylation and its subsequent dissociation from AMPK.Proc. Natl. Acad. Sci. U. S. A.108(12): 4788-4793

7.    Xu, M., Long, C., Chen, X., Huang, C.,Chen, S.#, and Zhu, B.#(2010). Partitioning of histone H3-H4 tetramers during DNA replication-dependent chromatin assembly.Science328(5974): 94-98.(#共同通讯作者).

8.    Cui, J., Yao, Q., Li, S., Ding, X., Lu, Q., Mao, H., Liu, L., Zheng, N.,Chen, S., and Shao, F. (2010). Glutamine deamidation and dysfunction of ubiquitin/NEDD8 induced by a bacterial effector family.Science329(5996): 1215-1218

9.    Tang, C. T., Li, S., Long, C., Cha, J., Huang, G., Li, L.,Chen, S.#, and Liu, Y.#(2009). Setting the pace of the Neurospora circadian clock by multiple independent FRQ phosphorylation events.Proc. Natl. Acad. Sci. U. S. A.106(26): 10722-10727.(#共同通讯作者).

10.  Huang, G.*,Chen, S.*, Li, S., Cha, J., Long, C., Li, L., He, Q., and Liu, Y. (2007). Protein kinase A and casein kinases mediate sequential phosphorylation events in the circadian negative feedback loop.Genes Dev.21(24): 3283-3295.(*共同第一作者).

2007年至今所有发表文章:

1.    Zhou, H., Lin, H., Chen, S., Becker, K., Yang, Y., Zhao, J., Kudla, J., Schumaker, K. S., and Guo, Y. (2014). Inhibition of the Arabidopsis Salt Overly Sensitive Pathway by 14-3-3 Proteins.Plant 购宝钱包

2.    Liu, Z. W., Shao, C. R., Zhang, C. J., Zhou, J. X., Zhang, S. W., Li, L.,Chen, S., Huang, H. W., Cai, T., and He, X. J. (2014). The SET domain proteins SUVH2 and SUVH9 are required for Pol V occupancy at RNA-directed DNA methylation loci.PLoS Genet.10(1): e1003948

3.    Zhou, M., Guo, J., Cha, J., Chae, M.,Chen, S., Barral, J. M., Sachs, M. S., and Liu, Y. (2013). Non-optimal codon usage affects expression, structure and function of clock protein FRQ.Nature495(7439): 111-115

4.    Yuan, G., Ma, B., Yuan, W., Zhang, Z., Chen, P., Ding, X., Feng, L., Shen, X.,Chen, S., Li, G., and Zhu, B. (2013). Histone H2A ubiquitination inhibits the enzymatic activity of H3 lysine 36 methyltransferases.J. Biol. Chem.288(43): 30832-30842

5.    Xia, S., Cheng, Y. T., Huang, S., Win, J., Soards, A., Jinn, T. L., Jones, J. D., Kamoun, S.,Chen, S., Zhang, Y., and Li, X. (2013). Regulation of transcription of nucleotide-binding leucine-rich repeat-encoding genes SNC1 and RPP4 via H3K4 trimethylation.Plant Physiol.162(3): 1694-1705

6.    Wang, G., Wang, X., Yu, H., Wei, S., Williams, N., Holmes, D. L., Halfmann, R., Naidoo, J., Wang, L., Li, L.,Chen, S., Harran, P., and Lei, X. (2013). Small-molecule activation of the TRAIL receptor DR5 in human cancer 购宝钱包 s.Nat. Chem. Biol.9(2): 84-89

7.    Tang, Z., Lin, M. G., Stowe, T. R.,Chen, S., Zhu, M., Stearns, T., Franco, B., and Zhong, Q. (2013). Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar satellites.Nature502(7470): 254-257

8.    Liu, Z., Wu, Y., Yang, F., Zhang, Y.,Chen, S., Xie, Q., Tian, X., and Zhou, J. M. (2013). BIK1 interacts with PEPRs to mediate ethylene-induced immunity.Proc. Natl. Acad. Sci. U. S. A.110(15): 6205-6210

9.    Lin, S., Yan, H., Li, L., Yang, M., Peng, B.,Chen, S., Li, W., and Chen, P. R. (2013). Site-specific engineering of chemical functionalities on the surface of live hepatitis D virus.Angew. Chem. Int. Ed. Engl.52(52): 13970-13974

10.  Liang, B., Peng, P.,Chen, S., Li, L., Zhang, M., Cao, D., Yang, J., Li, H., Gui, T., Li, X., and Shen, K. (2013). Characterization and proteomic analysis of ovarian cancer-derived exosomes.Journal of proteomics80C: 171-182

11.  Li, T. M., Chen, J., Li, X., Ding, X. J., Wu, Y., Zhao, L. F.,Chen, S., Lei, X., and Dong, M. Q. (2013). Absolute quantification of a steroid hormone that regulates development in Caenorhabditis elegans.Anal. Chem.85(19): 9281-9287

12.  Li, S., Zhang, L., Yao, Q., Li, L., Dong, N., Rong, J., Gao, W., Ding, X., Sun, L., Chen, X.,Chen, S.#, and Shao, F.#(2013). Pathogen blocks host death receptor signalling by arginine GlcNAcylation of death domains.Nature501(7466): 242-246.(#共同通讯作者).

13.  Zhang, C. J., Ning, Y. Q., Zhang, S. W., Chen, Q., Shao, C. R., Guo, Y. W., Zhou, J. X., Li, L.,Chen, S., and He, X. J. (2012). IDN2 and its paralogs form a complex required for RNA-directed DNA methylation.PLoS Genet.8(5): e1002693

14.  Yang, H., Han, Z., Cao, Y., Fan, D., Li, H., Mo, H., Feng, Y., Liu, L., Wang, Z., Yue, Y., Cui, S.,Chen, S., Chai, J., and Ma, L. (2012). A companion 购宝钱包 -dominant and developmentally regulated H3K4 demethylase controls flowering time in Arabidopsis via the repression of FLC expression.PLoS Genet.8(4): e1002664

15.  Yang, B., Wu, Y. J., Zhu, M., Fan, S. B., Lin, J., Zhang, K., Li, S., Chi, H., Li, Y. X., Chen, H. F., Luo, S. K., Ding, Y. H., Wang, L. H., Hao, Z., Xiu, L. Y.,Chen, S., Ye, K., He, S. M., and Dong, M. Q. (2012). Identification of cross-linked peptides from complex samples.Nat. Methods9(9): 904-906

16.  Xu, M., Wang, W.,Chen, S.#, and Zhu, B.#(2012). A model for mitotic inheritance of histone lysine methylation.EMBO reports13(1): 60-67.(#共同通讯作者).

17.  Xu, M.,Chen, S.#, and Zhu, B.#(2012). Investigating the 购宝钱包 cycle-associated dynamics of histone modifications using quantitative mass spectrometry.Methods Enzymol.512: 29-55.(#共同通讯作者).

18.  Wang, Z., Jiang, H.,Chen, S., Du, F., and Wang, X. (2012). The Mitochondrial Phosphatase PGAM5 Functions at the Convergence Point of Multiple Necrotic Death Pathways.购宝钱包 148(1-2): 228-243

19.  Sun, L., Wang, H., Wang, Z., He, S.,Chen, S., Liao, D., Wang, L., Yan, J., Liu, W., Lei, X., and Wang, X. (2012). Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 Kinase.购宝钱包 148(1-2): 213-227

20.  Rong, Y., Liu, M., Ma, L., Du, W., Zhang, H., Tian, Y., Cao, Z., Li, Y., Ren, H., Zhang, C., Li, L.,Chen, S., Xi, J., and Yu, L. (2012). Clathrin and phosphatidylinositol-4,5-bisphosphate regulate autophagic lysosome reformation.Nat. 购宝钱包 Biol.14(9): 924-934

21.  Lee, A. Y., Chen, W., Stippec, S., Self, J., Yang, F., Ding, X.,Chen, S., Juang, Y. C., and Cobb, M. H. (2012). Protein kinase WNK3 regulates the neuronal splicing factor Fox-1.Proc. Natl. Acad. Sci. U. S. A.109(42): 16841-16846

22.  Kong, Q., Qu, N., Gao, M., Zhang, Z., Ding, X., Yang, F., Li, Y., Dong, O. X.,Chen, S., Li, X., and Zhang, Y. (2012). The MEKK1-MKK1/MKK2-MPK4 kinase cascade negatively regulates immunity mediated by a mitogen-activated protein kinase kinase kinase in Arabidopsis.Plant 购宝钱包 24(5): 2225-2236

23.  Kato, M., Han, T. W., Xie, S., Shi, K., Du, X., Wu, L. C., Mirzaei, H., Goldsmith, E. J., Longgood, J., Pei, J., Grishin, N. V., Frantz, D. E., Schneider, J. W.,Chen, S., Li, L., Sawaya, M. R., Eisenberg, D., Tycko, R., and McKnight, S. L. (2012). 购宝钱包 -free formation of RNA granules: low complexity sequence domains form dynamic fibers within hydrogels.购宝钱包 149(4): 753-767

24.  Feng, F., Yang, F., Rong, W., Wu, X., Zhang, J.,Chen, S., He, C., and Zhou, J. M. (2012). A Xanthomonas uridine 5'-monophosphate transferase inhibits plant immune kinases.Nature485(7396): 114-118

25.  Chen, D., Fan, W., Lu, Y., Ding, X.,Chen, S., and Zhong, Q. (2012). A mammalian autophagosome maturation mechanism mediated by TECPR1 and the Atg12-Atg5 conjugate.Mol. 购宝钱包 45(5): 629-641

26.  Zhang, L., Ding, X., Cui, J., Xu, H., Chen, J., Gong, Y. N., Hu, L., Zhou, Y., Ge, J., Lu, Q., Liu, L.,Chen, S., and Shao, F. (2011). Cysteine methylation disrupts ubiquitin-chain sensing in NF-kappaB activation.Nature481(7380): 204-208

27.  Yuan, W., Xu, M., Huang, C., Liu, N.,Chen, S., and Zhu, B. (2011). H3K36 methylation antagonizes PRC2-mediated H3K27 methylation.J. Biol. Chem.286(10): 7983-7989

28.  Ye, X., Huang, N., Liu, Y., Paroo, Z., Huerta, C., Li, P.,Chen, S., Liu, Q., and Zhang, H. (2011). Structure of C3PO and mechanism of human RISC activation.Nat. Struct. Mol. Biol.18(6): 650-657

29.  Yang, P., Wang, Y., Chen, J., Li, H., Kang, L., Zhang, Y.,Chen, S., Zhu, B., and Gao, S. (2011). RCOR2 is a subunit of the LSD1 complex that regulates ESC property and substitutes for SOX2 in reprogramming somatic 购宝钱包 s to pluripotency.Stem 购宝钱包 s29(5): 791-801

30.  Xing, X. F., Li, H., Zhong, X. Y., Zhang, L. H., Wang, X. H., Liu, Y. Q., Jia, S. Q., Shi, T., Niu, Z. J., Peng, Y., Du, H., Zhang, G. G., Hu, Y., Lu, A. P., Li, J. Y.,Chen, S., and Ji, J. F. (2011). Phospholipase A2 group IIA expression correlates with prolonged survival in gastric cancer.Histopathology59(2): 198-206

31.  Wu, H., Chen, X., Xiong, J., Li, Y., Li, H., Ding, X., Liu, S.,Chen, S., Gao, S., and Zhu, B. (2011). Histone methyltransferase G9a contributes to H3K27 methylation in vivo.购宝钱包 Res.21(2): 365-367

32.  Wang, W., Chen, Z., Mao, Z., Zhang, H., Ding, X.,Chen, S., Zhang, X., Xu, R., and Zhu, B. (2011). Nucleolar protein Spindlin1 recognizes H3K4 methylation and stimulates the expression of rRNA genes.EMBO reports12(11): 1160-1166

33.  Sun, Q., Zhang, J., Fan, W., Wong, K. N., Ding, X.,Chen, S., and Zhong, Q. (2011). The RUN domain of rubicon is important for hVps34 binding, lipid kinase inhibition, and autophagy suppression.J. Biol. Chem.286(1): 185-191

34.  Shang, L.,Chen, S., Du, F., Li, S., Zhao, L., and Wang, X. (2011). Nutrient starvation elicits an acute autophagic response mediated by Ulk1 dephosphorylation and its subsequent dissociation from AMPK.Proc. Natl. Acad. Sci. U. S. A.108(12): 4788-4793

35.  Liu, Y., Tan, H., Tian, H., Liang, C.,Chen, S., and Liu, Q. (2011). Autoantigen La Promotes Efficient RNAi, Antiviral Response, and Transposon Silencing by Facilitating Multiple-Turnover RISC Catalysis.Mol. 购宝钱包 44(3): 502-508

36.  Kar, A., Fushimi, K., Zhou, X., Ray, P., Shi, C., Chen, X., Liu, Z.,Chen, S., and Wu, J. Y. (2011). RNA helicase p68 (DDX5) regulates tau exon 10 splicing by modulating a stem-loop structure at the 5' splice site.Mol. 购宝钱包 . Biol.31(9): 1812-1821

37.  Du, W., Lin, H.,Chen, S., Wu, Y., Zhang, J., Fuglsang, A. T., Palmgren, M. G., Wu, W., and Guo, Y. (2011). Phosphorylation of SOS3-like calcium-binding proteins by their interacting SOS2-like protein kinases is a common regulatory mechanism in Arabidopsis.Plant Physiol.156(4): 2235-2243

38.  Chen, X., Xiong, J., Xu, M.,Chen, S.#, and Zhu, B.#(2011). Symmetrical modification within a nucleosome is not required globally for histone lysine methylation.EMBO reports12(3): 244-251.(#共同通讯作者).

39.  Zhang, J., Li, W., Xiang, T., Liu, Z., Laluk, K., Ding, X., Zou, Y., Gao, M., Zhang, X.,Chen, S., Mengiste, T., Zhang, Y., and Zhou, J. M. (2010). Receptor-like cytoplasmic kinases integrate signaling from multiple plant immune receptors and are targeted by a Pseudomonas syringae effector.购宝钱包 host & microbe7(4): 290-301

40.  Xu, M., Long, C., Chen, X., Huang, C.,Chen, S.#, and Zhu, B.#(2010). Partitioning of histone H3-H4 tetramers during DNA replication-dependent chromatin assembly.Science328(5974): 94-98.(#共同通讯作者).

41.  Wang, Y., Li, J., Hou, S., Wang, X., Li, Y., Ren, D.,Chen, S., Tang, X., and Zhou, J. M. (2010). A Pseudomonas syringae ADP-ribosyltransferase inhibits Arabidopsis mitogen-activated protein kinase kinases.Plant 购宝钱包 22(6): 2033-2044

42.  Fang, M., Shen, Z., Huang, S., Zhao, L.,Chen, S., Mak, T. W., and Wang, X. (2010). The ER UDPase ENTPD5 promotes protein N-glycosylation, the Warburg effect, and proliferation in the PTEN pathway.购宝钱包 143(5): 711-724

43.  Fan, W., Tang, Z., Chen, D., Moughon, D., Ding, X.,Chen, S., Zhu, M., and Zhong, Q. (2010). Keap1 facilitates p62-mediated ubiquitin aggregate clearance via autophagy.Autophagy6(5): 614-621

44.  Cui, J., Yao, Q., Li, S., Ding, X., Lu, Q., Mao, H., Liu, L., Zheng, N.,Chen, S., and Shao, F. (2010). Glutamine deamidation and dysfunction of ubiquitin/NEDD8 induced by a bacterial effector family.Science329(5996): 1215-1218

45.  Yuan, W., Xie, J., Long, C., Erdjument-Bromage, H., Ding, X., Zheng, Y., Tempst, P.,Chen, S., Zhu, B., and Reinberg, D. (2009). Heterogeneous nuclear ribonucleoprotein L Is a subunit of human KMT3a/Set2 complex required for H3 Lys-36 trimethylation activity in vivo.J. Biol. Chem.284(23): 15701-15707

46.  Yao, Q., Cui, J., Zhu, Y., Wang, G., Hu, L., Long, C., Cao, R., Liu, X., Huang, N.,Chen, S., Liu, L., and Shao, F. (2009). A bacterial type III effector family uses the papain-like hydrolytic activity to arrest the host 购宝钱包 cycle.Proc. Natl. Acad. Sci. U. S. A.106(10): 3716-3721

47.  Yang, K., Shi, H. X., Liu, X. Y., Shan, Y. F., Wei, B.,Chen, S., and Wang, C. (2009). TRIM21 is essential to sustain IFN regulatory factor 3 activation during antiviral response.J. Immunol.182(6): 3782-3792

48.  Tang, C. T., Li, S., Long, C., Cha, J., Huang, G., Li, L.,Chen, S.#, and Liu, Y.#(2009). Setting the pace of the Neurospora circadian clock by multiple independent FRQ phosphorylation events.Proc. Natl. Acad. Sci. U. S. A.106(26): 10722-10727.(#共同通讯作者).

49.  Paroo, Z., Ye, X.,Chen, S., and Liu, Q. (2009). Phosphorylation of the human microRNA-generating complex mediates MAPK/Erk signaling.购宝钱包 139(1): 112-122

50.  Monaghan, J., Xu, F., Gao, M., Zhao, Q., Palma, K., Long, C.,Chen, S., Zhang, Y., and Li, X. (2009). Two Prp19-like U-box proteins in the MOS4-associated complex play redundant roles in plant innate immunity.PLoS Pathog5(7): e1000526

51.  Jia, G., Wang, W., Li, H., Mao, Z., Cai, G., Sun, J., Wu, H., Xu, M., Yang, P., Yuan, W.,Chen, S., and Zhu, B. (2009). A systematic evaluation of the compatibility of histones containing methyl-lysine analogues with biochemical reactions.购宝钱包 Res.19(10): 1217-1220

52.  Gao, M., Wang, X., Wang, D., Xu, F., Ding, X., Zhang, Z., Bi, D., Cheng, Y. T.,Chen, S., Li, X., and Zhang, Y. (2009). Regulation of 购宝钱包 death and innate immunity by two receptor-like kinases in Arabidopsis.购宝钱包 host & microbe6(1): 34-44

53.  Ganley, I. G., Lam du, H., Wang, J., Ding, X.,Chen, S., and Jiang, X. (2009). ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy.J. Biol. Chem.284(18): 12297-12305

54.  Sun, Q., Fan, W., Chen, K., Ding, X.,Chen, S., and Zhong, Q. (2008). Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol 3-kinase.Proc. Natl. Acad. Sci. U. S. A.105(49): 19211-19216

55.  Mi, S., Cai, T., Hu, Y., Chen, Y., Hodges, E., Ni, F., Wu, L., Li, S., Zhou, H., Long, C.,Chen, S., Hannon, G. J., and Qi, Y. (2008). Sorting of small RNAs into Arabidopsis argonaute complexes is directed by the 5' terminal nucleotide.购宝钱包 133(1): 116-127

56.  Zhu, Y., Li, H., Long, C., Hu, L., Xu, H., Liu, L.,Chen, S.#, Wang, D. C.#, and Shao, F.#(2007). Structural insights into the enzymatic mechanism of the pathogenic MAPK phosphothreonine lyase.Mol. 购宝钱包 28(5): 899-913.(#共同通讯作者).

57.  Zhang, J., Shao, F., Li, Y., Cui, H., Chen, L., Li, H., Zou, Y., Long, C., Lan, L., Chai, J.,Chen, S., Tang, X., and Zhou, J. M. (2007). A Pseudomonas syringae effector inactivates MAPKs to suppress PAMP-induced immunity in plants.购宝钱包 host & microbe1(3): 175-185

58.  Xing, W., Zou, Y., Liu, Q., Liu, J., Luo, X., Huang, Q.,Chen, S., Zhu, L., Bi, R., Hao, Q., Wu, J. W., Zhou, J. M., and Chai, J. (2007). The structural basis for activation of plant immunity by bacterial effector protein AvrPto.Nature449(7159): 243-247

59.  Li, H., Xu, H., Zhou, Y., Zhang, J., Long, C., Li, S.,Chen, S., Zhou, J. M., and Shao, F. (2007). The phosphothreonine lyase activity of a bacterial type III effector family.Science315(5814): 1000-1003

60.  Huang, G.*,Chen, S.*, Li, S., Cha, J., Long, C., Li, L., He, Q., and Liu, Y. (2007). Protein kinase A and casein kinases mediate sequential phosphorylation events in the circadian negative feedback loop.Genes Dev.21(24): 3283-3295.(*共同第一作者).