|Budget Amount *help
¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 1999 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 1998 : ¥2,000,000 (Direct Cost : ¥2,000,000)
In eukaryotic cell cycle, mitosis is tightly coordinated and is regulated both temporally and spatially with dynamic mophological changes. To ensure this, cell must disassemble nuclear envelope and cytoskeleton, physically segregate the sister chromatid which is duplicated during S phase to opposite poles of mitotic spindle, reassemble two nuclei, and undergo cytokinesis to divide organelles, cytoplasm, and other cell contents into two daughter cells. Accurate segregation or distribution of chromosomes is critical for cell viability and normal cellular function, and missegregation and unequal distribution can result in aneuploidy which has been associated with tumorigenesis in multicellular oraganisms. Therefore, it is important to elucidate how complex mitotic progression is regulated and which molecules are involved.
In this research project, the findings are as follows :
1. A new mammalian kianse gene family belonging to A-kinase was identified. These kianses, AIM-1 and its related kinases, are structually related to yeast Ipl1 and Drosophila Aurora.
2. The family genes include the genes expressed in mitotic cells and in non-dividing human heart tissue.
3. A kinase -inactive AIM-1 induced multinuclear cells in normal diploid fibroblasts and the AIM-1 expression was downregulated during multinuclear formation processes of the megakaryocytic differentiation in human leukemic cells. Thus, AIM-1 was suggested to play an important role in a certain aspect of ploidy maidenance of mammalian cells.
4. AIM-2/STK15 was found to be another kianse localized in spindle pole suggesting certain function during spindle pole separation in mitosis.
5. AIM-1 and AIM-2/STK15 were found to be overexpressed in human colorectal cancer.