调节生物学  Regulatory Biology

简 历: 男，1963年生，博士．1984年毕业于厦门大学生物系．1985年由CUSBEA项目赴美留学．1991年获美国德克萨斯大学西南医学中心生物化学博士．1991～1995年Howard Hughes Institute at UCSD博士后。1995～2001年新加坡国立大学分子与细胞生物研究所实验室主任．2001年至今为厦门大学生命科学学院“长江学者”、博士生导师，现任生命科学学院院长．

1984, B.Sc. Xiamen University; 1991, Ph.D., UT Southwestern Medical Center at Dallas; 1991-1995: Postdoctoral Fellow at the Howard Hughes Medical Institute, UCSD; 1995-2001: Principal Investigator, IMCB, Singapore; 2001-Present: Professor, Cheung Kong Scholar, Xiamen University; 2003 to Present, Dean, School of Life Sciences, Xiamen University.

主要研究领域: 致力于细胞生长发育及调控机理方面的信号转导研究．

研究摘要: 体轴发育抑制因子Axin是Wnt信号途径的负调控子, 其变异可导致复轴及癌症发生．我们实验室发现，Axin是一种可以激活JNK MAP激酶的骨架蛋白，并独家阐明了整个信号通路的分子与生化机理，发现Axin是通过MEKK1/4以及其下游激酶MKK4/7激酶JNK．并发现Axin对JNK激酶的活化可导致细胞程序性死亡，证明Axin是一个抑癌基因．最近，我们又发现它能结合p53及其调节因子结合，增强p53的磷酸化从而激活p53诱导细胞死亡；至此，我们对Axin活化JNK和作为抑癌因子这一系列信号通路的结构基础和分子机制有了系统的研究和成果．

Our research lies in the broad area of the molecular mechanisms that underlie cell proliferation, differentiation, and development. We have delineated a signaling pathway, in that Axin, an axis inhibitor, binds to MEKK1/4 and activates the JNK MAP kinases via MKK4/7. An intriguing aspect of the Axin/JNK pathway is that Axin utilizes multiple domains for JNK activation. More recently, we found that Axin interacts with the nuclear serine/threonine kinase HIPK2 and enhances its kinase activity towards p53, promoting p53-dependent transcriptional activity and apoptosis. Axin is thus a master scaffold for multiple signaling pathways that control body development, and cell proliferation and death.

代表性论文

1.Lin, C.R., Lin, S.-C., Chang, C.P., and Rosenfeld, M.G.  Pit-1-dependent expression of the receptor for growth hormone releasing factor mediates pituitary cell growth.  Nature 360:765-768, 1992.

2.Lin. S.-C., et al.  Molecular basis of the little mouse phenotype and implication for cell type-specific growth (Article).  Nature 364:208-213, 1993.

3.Lin. S.-C., et al. Pituitary ontogeny of the Snell dwarf mouse reveals Pit-1-Independent and Pit-1-dependent origins of thyrotrope.  Development 120:515-522, 1994.

4.Kamei, Y., Xu, L., Heinzel, T., Torchia, J., Kurokawa, R., Gloss, B., Lin, S.-C., Heyman, R.A., Rose, D.W., Glass, C.K., and Rosenfeld, M.G.  A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors.  Cell 85:403-414, 1996.

5.Zhang, Y., Wang, X., Neo, S.Y., Han, J., and Lin, S.-C. Axin forms a complex with MEKK1 and activates c-Jun N-terminal kinase/stress-activated protein kinase through domains distinct from Wnt signaling.  J. Biol. Chem. 274:35247-35254, 1999.

6.Zhang, Y., Qiu, W.J. Chan, S.C., Han, J., He, X., and Lin, S.-C.  Casein kinase I and Casein kinase II Differentially Regulate Axin Function in Wnt and JNK pathways. J. Biol. Chem. 277, 17706-17712, 2002.

7.Rui, H.L., Fong, E., Xu, Z., Zhou, H.M., and Lin, S.C. Sumolyation is required for Axin activation of JNK, but has not effect on Wnt signalling. J. Biol. Chem. 277, 42981-6, 2002

8.Jin, L.H.,  Shao, Q.J., Luo, W., Ye, Z.Y., Li, Q., and Lin, S.C. Detection of Point Mutations of the AXIN1 Gene in Colorectal Cancers. Int. J. Cancer. 107, 696-9, 2003

9.Zhou, Z., Yon, T.S., Chen, Z., Guo, K., Ng, C.P., Ponniah, S., Lin, S.C., Hong, W., Li, P. Cidea-deficient mice have lean phenotype and are resistant to obesity. Nature Genetics 35, 49-56, 2003

10.Luo, W., Ng, W., Jin, L.H., and Ye, Z.Y., and Lin, S.C. Axin utilizes distinct regions for competitive MEKK1 and MEKK4 binding, and JNK activation. J Biol Chem. 278, 37451-8, 2003

课题组成员(Lab. Staff)
    叶志云: 学士，高级工程师．从事生化与分子生物学研究．  
    李勤喜: 博士，讲师．从事细胞信号传导的研究．