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
e-mail: brumoe00@bf.jcu.cz
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.
Acknowledgement
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.