Biochemistry and molecular Biology
1989-1993, BSc, Shenyang Pharmaceutical University, China
1997-2000, M.D., Shenyang Pharmaceutical University, China
2000-2003, Ph.D., Beijing Normal University, China
2003-2006, Lecturer, Beijing Normal University, China
2006-2015, Asscociate Professor, Beijing Normal University, China
2010-2011, Visiting Scholar, National Institute of Health, USA
2015-present, Professor, Beijing Normal University, China
Calcineurin (CN) is a serine/threonine phosphatase which is activated by calcium/ calmodulin. It plays critical roles in many biological processes, including the immune response, learning and memory. Upon activation, CN dephosphorylates NFAT, which then translocate to the nucleus. In the nucleus, NFAT regulates gene transcription such as IL-2 which is related to the immune response. Two domains of an NFAT protein that interact with CN have been defined: the PxIxIT motif, situated near the N terminus of the regulatory region of NFAT and the LxVP motif, located near the C terminus. We have studied and reported some PxIxIT-type and LxVP-type motifs, such as NFAT, regulators of calcineurin (RCAN1), transcription factor EB (TFEB) and dynamin-related protein 1 (Drp1). Based on the affinity ability and inhibitory effect of these motifs on CN, we designed some peptide inhibitors against CN/NFAT interaction, which has two binding sites with CN. Those peptides have two docking sites on CN and the most potent inhibitory effect on CN. We plan to use quantitative proteomic analysis to find new substrates and targeting protein of CN. The research on the binding motif of CN and the transcription factor EB related to autophagy is in progress. We are going to improve the active polypeptide and further study its function in vitro and in vivo.
♦ Research Articles
1. Wang L#, Cheng N#, Wang P, Li J, Jia A, Li W, Zhang N, Yin Y, Tong L, Wei Q, Liu G, Li Z*, Luo J*. (2020) A novel peptide exerts more potent immunosuppression by blocking the two-site interaction of NFAT with calcineurin. J. Biol. Chem, 295(9) 2760-2770.
2. Liu Y, Xue X, Zhang H, Che X, Luo J, Wang P, Xu J, Xing Z, Yuan L, Liu Y, Fu X, Su D, Sun S, Zhang H, Wu C and Yang J. (2019) Neuronal-targeted TFEB rescues dysfunction of the autophagy-lysosomal pathway and alleviates ischemic injury in permanent cerebral ischemia. Autophagy. 15, 493-509.
3. Shi X#, Sun Y#, Wang P, Gu L, Wang L, Yang H, Wei Q, Li Z, Luo J*. (2018) The interaction between calcineurin and a-synuclein is regulated by calcium and calmodulin. Biochem. Biophys. Res. Commun. 496, 1109-1114.
4. Song R#, Li J#, Zhang J#, Wang L, Tong L, Wang P, Yang H, Wei Q, Cai H and Luo J*. (2017) Peptides derived from transcription factor EB bind to calcineurin at a similar region as the NFAT-type motif. Biochimie. 142, 158-167.
5. Zhao Y#, Zhang J#, Shi X#, Li J, Wang R, Song R, Wei Q, Cai H, Luo J*. (2016) Quercetin targets the interaction of calcineurin with LxVP-type motifs in immunosuppression. Biochimie. 127, 50-58.
6. Luo J, Sun L, Lin X, Liu G, Yu J, Parisiadou L, Xie C, Ding J, Cai H. (2014) A calcineurin- and NFAT-dependent pathway is involved in a-synuclein-induced degeneration of midbrain dopaminergic neurons. Hum. Mol. Genet. 23, 6567-6574.
7. Ma B, Yu J, Xie C, Sun L, Lin S, Ding J, Luo J, Cai H. (2015) Toll-Like Receptors Promote Mitochondrial Translocation of Nuclear Transcription Factor Nuclear Factor of Activated T-Cells in Prolonged Microglial Activation. J. Neurosci. 35(30), 10799-10814.
8. Liu G, Yu J, Ding J, Xie C, Sun L, Rudenko I, Zheng W, Sastry N, Luo J, Rudow G, Troncoso JC, Cai H. (2014) ALDH1A1 defines and protects subpopulation of nigrostriatal dopaminergic neurons. J. Clin. Invest. 124, 3032-3046.
College of Life Sciences,
Beijing Normal University,
P. R. China
Tel. : +86-10-58808197