陈瑞川

陈瑞川 CHEN Ruichuan, Ph.D.

教授，博士生导师，课题组组长

课题组：转录调控与疾病

(Transcription Regulation and Dieases)

电  话：+86- 592-2184533+86- 592-2184533

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。

1983-2002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 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至今厦门大学生命科学学院教授。

1983, BS, East China University of Science and Technology;

2000, Ph.D, Xiamen University;

2002-2005, Dept. of Molecular and Cellular Biology, University of California at Berkeley, Visiting Scholar;

2008 to present, School of Life Sciences, Xiame

研究领域（Research Area）

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。

Consisting of Cdk9 and cycling 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.

代表性论文(Selected Publications)

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 RESSEARCH, 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 RESSEARCH, 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. and Qiang Zhou. A capping independent function of MePCE in stabilizing 7SK snRNA and facilitating the assembly of 7SK snRNP. NUCLEIC ACIDS RESSEARCH, 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, 2006). Gene Expression and Regulation, Chapter 14; HEPC and Springer Press, 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）

主持在研基金项目(Ongoing grants)

1、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

2、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

3、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