Aurora- and Ipl1-like midbody-associated protein (AIM-1) is a serine/threonine kinase that is structurally related to Drosophila aurora and Saccharomyces cerevisiae Ipl1, both of which are required for chromosome segregation. A kinase-negative form of AIM-1 inhibits the formation of cleavage furrow without affecting nuclear division, indicating that the gene controls entry into cytokinesis during M phase in mammalian cells. A human gene that encodes the protein AIM-1 was overexpressed in colorectal and other tumor cell lines. The regulation of AIM-1 expression was cell cycle dependent in normal and tumor cells, and the maximum accumulation was observed at G2-M. Exogenous overexpression of wild-type AIM-1 produced multinuclearity in human cells, suggesting that the excess amount of AIM-1 had a dominant-negative effect on the overexpressing cells. In long-term culture of AIM-1-overexpressing cells, multiple nuclei in a cell were occasionally fused, and then an increased ploidy and aneuploidy were induced. Thus, the overexpression of AIM-1 in colorectal tumor cell lines is thought to have a causal relationship with multinuclearity and increased ploidy. Cytokinesis error caused by AIM-1 overexpression is a major factor in the predisposition of tumor cells to the perturbation of chromosomal integrity that is commonly observed in human neoplasia. Thus, defects of pathways essential for mitotic regulation are important during human cancer development.


This work was supported by Grants-in-Aid for Scientific Research 10151234, 10480135, and 10680672 from the Ministry of Education, Science, Sports and Culture of Japan (to M. T. and F. S.), a grant from the Japan Atomic Energy Research Institute under contract to the Nuclear Safety Research Association (to F. S. and M. T.), a grant from the Electric Technology Research Foundation of Chugoku in Japan (to F. S. and M. T.), and a grant from the Kanazawa Medical University High-Technology Center (to T. O.).

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