课题组长：陈瑞川
Ruichuan Chen, Ph.D

转录调控与疾病
  Transcription Regulation and Dieases

陈瑞川简历：
    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；2005至今厦门大学生命科学学院副教授。

    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: 2005 to present, School of Life Sciences, Xiamen University, Associate Porfessor.

主要研究领域（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 (positive transcription elongation factor 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。

    The elongation stage of eukaryotic transcription is a highly dynamic and regulated process that couples transcription with other major gene expression events. The studies of elongation have benefited greatly from the analyses of P-TEFb. Consisting of Cdk9 and cyclin T, P-TEFb was first identified as a general transcription factor required for the expression of a vast array of protein-coding genes. It was subsequently found to play a key role in HIV replication. Besides HIV replication, recent studies have also implicated a key role for P-TEFb in promoting the onset and progression of cardiac hypertrophy and probably also breast cancer.
    We have recently identified both positive and negative regulators that can alternately interact with P-TEFb to control its activity and affect transcription. Under normal growth conditions in HeLa cells, about half of nuclear P-TEFb are sequestered in an inactive complex that also contains the 7SK snRNA and the HEXIM1 protein. The other half of nuclear P-TEFb exist in a separate complex with the bromodomain protein Brd4 which can recruit P-TEFb to promoter and enables P-TEFb to stimulate RNA polymerase II mediated transcription. Our studies also revealed that the formation and disruption of inactive complex of P-TEFb is controlled by phosphorylation and de-phosphorylation on P-TEFb. The most recent studies of our lab have revealed that PP2B and PP1 could cooperatively disrupt inactive compled to release P-TEFb for transcription in response to Ca ²⁺ signaling.
    We are currently performing structure-function analyses of the P-TEFb-containing complexes to study the mechanisms by which P-TEFb activity can be positively modulated. We are also trying to identy 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. Ruichuan Chen*#, Min Liu#, Huan Li#, Yuhua Xue, Wanichaya N. Ramey, Nanping Ai, 1Haohong Luo, Ying Zhu, Nan Zhou and Qiang Zhou*. PP2B and PP1 cooperate to dephosphorylate Cdk9 T-loop and release P-TEFb from 7SK snRNP in response to calcium signaling. GENES & DEVELOPMENT. 2008, 22: 1356-1368 (*Co-coresponding author, #Co-first author)
2. 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. NUCLEAR ACID RESEARCH, 2007, 35(6):2003-12
3. 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
4. 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
5. 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
6. 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
7. 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 (#Co-first author)
8. 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.
9. 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. (#Co-first author)

专利
    Qiang Zhou, Jasper H. N. Yik, Ruichuan Chen. HEXIM1 as a Suppressor of HIV Replication and Cardiac Hypertrophy.  (United States Patent, No: 7087433. November 7, 2006)

课题组成员(Lab Associates)

周   强（Qiang Zhou）: 闽江学者讲座教授、博导
个人网页：/teacher/teachersy/2006-09-21/974.html
Prof of Biochemistry, Dept. of Molecular and Cellular Biology, University of Califormia at Berkeley
Page: http://mcb.berkeley.edu/faculty/BMB/zhouq.html

刘润忠 (Runzhong Liu)：副教授 (Associate Professor)
个人网页：/teacher/teachersy/2007-05-09/1374.html
研究兴趣：主要从事神经退行性疾病如Alzheimer’s disease(AD)病理机制以及正性转录延伸因子（P-TEFb）在神经干细胞中的转录调节作用机理研究。特别是HIV-1 Tat蛋白对大脑神经元中P-TEFb的调节对神经退行性疾病的影响。
      Our research focuses on understanding the molecular events that underlie the pathogenesis of neurodegenative diseases such as Alzheimer’s disease (AD) and the mechanism of positive transcriptional elongation factor b(P-TEFb) regulation transcription in neural stem cells. Especially on the mechanism of the HIV-1 Tat protein regulation P-TEFb of neurons for neurodegenative diseases.

转录调控与疾病实验室
厦门大学生命科学学院，生物2馆101室，厦门 361005

Laboratory of
Transcription Regulation and Diease

Rm101, Bld II, School of Life Sciences, Xiamen University, Xiamen 361005, China
Tel：   (0592)-2184533
Email:  chenrc@xmu.edu.cn
        liurz@xmu.edu.cn

本实验室欢迎有志于科学碳素研究的本科生、硕士生、博士生和博士后加盟！