陈瑞川

陈瑞川 (CHEN Ruichuan, Ph.D.) ADSFAEQWER353423413434

教授，博士生导师，课题组组长 ADSFAEQWER353423413434

课题组：转录调控与疾病 ADSFAEQWER353423413434

(Transcription Regulation and Diseases)

电话：+86-592-2184533

ADSFAEQWER353423413434

E-mail：chenrc@xmu.edu.cn

1983年毕业于华东理工大学生化工程系，获学士学位；2000年毕业于厦门大学生物系，获博士学位。

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1983-2002年，厦门大学抗癌研究中心，历任实习研究员、助理研究员和副研究员；2002-2005年，美国加州大学伯克利分校分子与细胞生物学系，访问学者；2008年至今，厦门大学生命科学学院教授。 ADSFAEQWER353423413434

真核基因的转录表达是通过一系列复杂而精致的机制来完成的。近年来在转录延伸及其调控机制研究上的重大突破得益于正性转录延伸因子b (P-TEFb)的发现及其功能的研究。P-TEFb是由CDK9及其调节亚基CyclinT组成的具有激酶活性的基本转录延伸因子，是调控真核基因转录由起始状态进入延伸阶段的必需因子，参与绝大多数基因的转录表达。同时，P-TEFb也是人类艾滋病病毒转录复制的必需因子之一。新近报道表明P-TEFb活性异常与心肌肥大有直接的关系、与肿瘤的发生和发展也有密切的关系。因此，P-TEFb活性调控分子机制的研究及其重要，近年已成为该研究领域的主要热点。我们的主要研究目标是揭示P-TEFb活性调控的分子机制，并寻找调控其活性的细胞信号途径，及其对HIV复制、心肌肥大和肿瘤细胞生长与分化的影响。

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Consisting of Cdk9 and cyclin T, P-TEFb plays key roles both in the expression of most cellular genes and in pathogenesis, such as HIV replication, cardiac hypertrophy and carcinogenesis. Since 2002, we have identified both positive and negative regulators that can alternately interact with P-TEFb to control its activity and affect transcription. Recent study revealed that PP2B and PP1 could cooperatively disrupt inactive complex to release P-TEFb for transcription in response to Ca2+ signaling. Currently, we are performing structure-function analyses of the P-TEFb-containing complexes to study the mechanisms by which P-TEFb activity can be positively modulated. The second direction is revealing the signal and molecular mechanism of regulating the recruitment of active P-TEFb complex. We are also trying to identify more signaling pathways that control the formation and disruption of the P-TEFb complexes and the involvement of these pathways in cell growth/differentiation, HIV replication and other diseases.

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1. Xiangming Hu, Xiaodong Lu, Feng Ding, Nanping Ai, Zhenhua Cao, Yannan Li, Jiangfang Liu, Kai Liu, Huiping Wang, Chao Zhou, Shanwen Wu, Aidong Han, Runzhong Liu and Ruichuan Chen. Histone crosstalk between H3S10ph and H4K5ac/K8ac regulates Brd4 activation for inducible gene expression. Nucleic Acids Research, 2013 (in revision).
2. Nanping Ai, Xiangming Hu, Feng Ding, Bingfei Yu, Huiping Wang, Xiaodong Lu, Kai Zhang, Yannan Li, Aidong Han, Wen Lin, Runzhong Liu and Ruichuan Chen. Signal-induced Brd4 release from chromatin is essential for its role transition from chromatin-targeting to transcriptional regulation. Nucleic Acids Research, 2011; 39(22): 9592-9604.
3. Ruichuan Chen, Min Liu, Kai Zhang, Qiang Zhou. Isolation and functional characterization of P-TEFb-associated factors that control general and HIV-1 transcriptional elongation. Methods, 2011;53(1):85-90.
4. Yuhua Xue, Zhiyuan Yang, Ruichuan Chen, Qiang Zhou. A capping independent function of MePCE in stabilizing 7SK snRNA and facilitating the assembly of 7SK snRNP. Nucleic Acids Research, 2010, 38(2):360-369.
5. Ruichuan Chen, Min Liu, Huan Li, Yuhua Xue, Wanichaya N. Ramey, Nanhai He, Nanping Ai, Haohong Luo, Ying Zhu, Nan Zhou and Qiang Zhou. PP2B and PP1alpha cooperatively disrupt 7SK snRNP to release P-TEFb for transcription in response to Ca2+ signaling. Genes & Development, 2008 May 15; 22(10):1356-68.
6. Matjaz Barboric, Jasper H.N. Yik, Nadine Czudnochowski, ZhiyuanYang, Ruichuan Chen, Xavier Contreras, Matthias Geyer, B. Matija Peterlin and Qiang Zhou. Tat competes with HEXIM1 to increase the active pool of P-TEFb for HIV-1 transcription. Nucleic Acids Research, 2007, 35(6):2003-12.
7. Ruichuan Chen and Qiang Zhou. HIV Tat and the control of transcriptional elongation (Review). Gene Expression and Regulation, Chapter 14; HEPC and Springer Press, 2006, pp239-256.
8. Wen-Jun He, Ruichuan Chen, Zhiyuan Yang and Qiang Zhou. Regulation of two key nuclear enzymatic activities by the 7SK small nuclear RNA. Cold Spring Harb Symp Quant Biol, 2006, 71: 301-11.
9. Jasper H. N. Yik, Ruichuan Chen, Andrea C. Pezda, and Qiang Zhou. Compensatory contributions of HEXIM1 and HEXIM2 in maintaining the balance of active and inactive P-TEFb complexes for control of transcription. Journal of Biological Chemistry, 2005, 280(16):16368-76.
10. Zhiyuan Yang, Jasper H. N. Yik, Ruichuan Chen, Moon Kyoo Jang, Keiko Ozato, and Qiang Zhou. Recruitment of P-TEFb for stimulation of transcriptional elongation by bromodomain protein Brd4. Molecular Cell, 2005, 19(4):535-545.
11. Ruichuan Chen, Zhiyuan Yang, and Qiang Zhou. Phosphorylated P-TEFb is tagged for inhibition through association with 7SK snRNA. Journal of Biological Chemistry, 2004;279(6), 4153-4160.
12. Jasper H. N. Yik, Ruichuan Chen, Andrea C. Pezda, Craig S. Samford, and Qiang Zhou. A human immunodeficiency virus type 1 Tat-like arginine-rich RNA-binding domain is essential for HEXIM1 to inhibit RNA polymerase II transcription through 7SK snRNA-mediated inactivation of P-TEFb. Molecular and Cellular Biology, 2004; 24 (12): 5094-5105 (共同第一作者).
13. Jasper H. N. Yik, Ruichuan Chen, Rieko Nishimura, Jennifer L. Jennings, Andrew J. Link and Qiang Zhou. Inhibition of P-TEFb (CDK9/cyclin T) kinase and RNA polymerase II transcription by the coordinated actions of HEXIM1 and 7SK snRNA. Molecular Cell, 2003;12(4), 971-982 (共同第一作者).

• 国家基金重点项目：P-TEFb重活化调控机制及其对细胞周期的影响（项目编号：30930046；经费总额：165万元）
• 国家基金面上项目：Brd4应激活化的调控机制及其意义（项目编号：31270809；经费总额：80万元）
• 973项目子课题：基因转录延伸及终止因子对APA的调节作用和机制（课题编号：2013CB917802；经费总额：241万元）

• Hu X, Lu X, Ding F, et al. Histone crosstalk between H3S10ph and H4K5ac/K8ac regulates Brd4 activation for inducible gene expression. Nucleic Acids Res, 2013 (in revision).
• Ai N, Hu X, Ding F, et al. Signal-induced Brd4 release from chromatin is essential for its role transition from chromatin-targeting to transcriptional regulation. Nucleic Acids Res, 2011;39(22):9592-9604.
• Chen R, Liu M, Zhang K, Zhou Q. Isolation and functional characterization of P-TEFb-associated factors that control general and HIV-1 transcriptional elongation. Methods, 2011;53(1):85-90.
• Xue Y, Yang Z, Chen R, Zhou Q. A capping independent function of MePCE in stabilizing 7SK snRNA and facilitating the assembly of 7SK snRNP. Nucleic Acids Res, 2010;38(2):360-369.
• Chen R, Liu M, Li H, et al. PP2B and PP1alpha cooperatively disrupt 7SK snRNP to release P-TEFb for transcription in response to Ca2+ signaling. Genes Dev, 2008;22(10):1356-1368.
• Barboric M, Yik JHN, Czudnochowski N, et al. Tat competes with HEXIM1 to increase the active pool of P-TEFb for HIV-1 transcription. Nucleic Acids Res, 2007;35(6):2003-2012.
• Chen R, Zhou Q. HIV Tat and the control of transcriptional elongation. In: Gene Expression and Regulation. HEPC and Springer Press, 2006:239-256.
• He WJ, Chen R, Yang Z, Zhou Q. Regulation of two key nuclear enzymatic activities by the 7SK small nuclear RNA. Cold Spring Harb Symp Quant Biol, 2006;71:301-311.
• Yik JHN, Chen R, Pezda AC, Zhou Q. Compensatory contributions of HEXIM1 and HEXIM2 in maintaining the balance of active and inactive P-TEFb complexes for control of transcription. J Biol Chem, 2005;280(16):16368-16376.
• Yang Z, Yik JHN, Chen R, et al. Recruitment of P-TEFb for stimulation of transcriptional elongation by bromodomain protein Brd4. Mol Cell, 2005;19(4):535-545.
• Chen R, Yang Z, Zhou Q. Phosphorylated P-TEFb is tagged for inhibition through association with 7SK snRNA. J Biol Chem, 2004;279(6):4153-4160.
• Yik JHN, Chen R, Pezda AC, et al. A human immunodeficiency virus type 1 Tat-like arginine-rich RNA-binding domain is essential for HEXIM1 to inhibit RNA polymerase II transcription through 7SK snRNA-mediated inactivation of P-TEFb. Mol Cell Biol, 2004;24(12):5094-5105.
• Yik JHN, Chen R, Nishimura R, et al. Inhibition of P-TEFb (CDK9/cyclin T) kinase and RNA polymerase II transcription by the coordinated actions of HEXIM1 and 7SK snRNA. Mol Cell, 2003;12(4):971-982.
• Zhou Q, Yik JHN. The Yin and Yang of P-TEFb regulation: implications for human immunodeficiency virus gene expression and global control of cell growth and differentiation. Microbiol Mol Biol Rev, 2006;70(3):646-659.
• Peterlin BM, Price DH. Controlling the elongation phase of transcription with P-TEFb. Mol Cell, 2006;23(3):297-305.
• 陈瑞川, 周强. 转录延伸因子P-TEFb的调控机制. 中国生物化学与分子生物学报, 2005;21(6):707-712.
• 刘敏, 陈瑞川. Brd4在转录调控和疾病中的作用. 生命科学, 2012;24(4):360-366.