Complex regulation and nuclear localization of JRK protein.
The mouse jerky gene and its human orthologue, JRK/ JH8, encode a putative DNA-binding protein with homology to the CENP-B (centromere-binding protein B). Disruption of the mouse jerky gene by transgene insertion causes generalized recurrent seizures reminiscent of human idiopathic generalized epilepsy. In addition (and similar to a cenp-b null mouse) jerky null mice exhibit postnatal weight loss and reduced fertility. Using fluorescence confocal microscopy, the cellular localization of a JRK-GFP fusion (where GFP stands for green fluorescent protein) was investigated in HeLa cells. JRK-GFP has a dynamic expression pattern in the interphase nucleus, localizing in a small number of punctate nuclear foci and in the nucleolus. The JRK-GFP foci number changes during the cell cycle, but a distinct pattern of three JRK-GFP foci is observed at G(2). The endogenous protein behaves in a similar manner to the GFP-fusion protein. JRK-GFP was found to co-localize with CREST antigens (which recognize the centromere-binding proteins, CENP-A, -B and -C) through S and G(2) phases of interphase and co-localized completely with a subset of PML nuclear bodies at G(2). We speculate that JRK protein associates with a specific chromosomal centromeric locus in G(2), where it associates fully with PML bodies. Research is underway to identify this locus.[1]References
- Complex regulation and nuclear localization of JRK protein. Waldron, R., Moore, T. Biochem. Soc. Trans. (2004) [Pubmed]
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