Ruichuan CHEN, Ph.D.
1983, B.Sc., 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-present, School of Life Sciences, Xiamen.
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.
1. Liu M, Li Y, Chen R*. CaMKII: Do Not Work Too Hard in the Failing Heart. J Pathol. 2015, 235(5): 669-71.
2. Hu X, Lu X, Liu R, Ai N, Cao Z, Li Y, Liu J, Yu B, Liu K, Wang H, Zhou C, Wang Y, Han A, Ding F, Chen R*. Histone Crosstalk Connects Protein Phosphatase 1α (PP1α) and Histone Deacetylase (HDAC) Pathways to Regulate the Functional Transition of Bromodomain-containing 4 (Brd4) for Inducible Gene Expression. J Biol Chem. 2014, 289(33): 23154-67.
3. Wang W, Yao X, Huang Y, Hu X, Liu R, Hou D, Chen R, Wang G. Mediator MED23 regulates basal transcription in vivo via an interaction with P-TEFb.Transcription. 2013, 4(1): 39-51.
4. 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.
5. 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.
6. 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.
7. 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, 15; 22(10):1356-68.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.