Structural And Functional Characterization Of Human Protein Kinase CKI Epsilon


E. Brumovská1 , P. Houfková1, S. Trantírková1, C. Modak2, T. Doležal1  and L. Trantírek1


1Laboratory Of Structural Biology, Faculty Of Biological Sciences, University Of South Bohemia, Branišovská 31, 370 05 České Budějovice, Czech Republic

2 Developmental Biology Center and Department of Medicine, University of California-Irvine, Irvine, California, USA



Casein kinase I epsilon (CKIe) is one of the crucial components of Wnt signaling pathway that is required for normal development and cell proliferation. However, the role of CKIe in this signaling remains still unclear. It has been shown that mutations in some genes encoding proteins regulating the Wnt cascade (b-catenin, axin, APC) are common in dysregulated development and multiple cancers. Recently, Fuja et al. (2004) identified eleven point mutations in gene for CKIe in human breast cancer cells. In this project, we would like to address the effect of mutations on casein kinase I epsilon 3D structure and its activity. In parallel, we plan to identify proteins, which stably associate with CKIe under in vivo conditions and potentially characterize the topology of the CKIe complex. These investigations will provide a molecular basis for understanding of CKIe function and for design of drugs modulating CKIe activity.




This work was supported by Grant Agency of the Czech Republic (301/07/0814 ).


Fuja TJ, Lin F, Osann KE, Bryant PJ (2004): Somatic mutations and altered expression of the candidate tumor suppressors CSNK1 epsilon, DLG1, and EDD/hHYD in mammary ductal carcinoma. Cancer Res. 64(3):942-51.