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AIM-1: a mammalian midbody-associated protein required for cytokinesis
Y Terada1, M Tatsuka, F Suzuki
1Louis Pasteur Center for Medical Research, Department of Molecular Biology, 103-5 Tanaka Monzencho, Sakyo-ku, Kyoto 606. terada@fas.harvard.edu
Abstract:
Mitosis is a highly coordinated process that assures the fidelity of chromosome segregation. Errors in this process result in aneuploidy which can lead to cell death or oncogenesis. In this paper we describe a putative mammalian protein kinase, AIM-1 (Aurora and Ipl1-like midbody-associated protein), related to Drosophila Aurora and Saccharomyces cerevisiae Ipl1, both of which are required for chromosome segregation. AIM-1 message and protein accumulate at G2/M phase. The protein localizes at the equator of central spindles during late anaphase and at the midbody during telophase and cytokinesis. Overexpression of kinase-inactive AIM-1 disrupts cleavage furrow formation without affecting nuclear division. Furthermore, cytokinesis frequently fails, resulting in cell polyploidy and subsequent cell death. These results strongly suggest that AIM-1 is required for proper progression of cytokinesis in mammalian cells.
Insights
A new protein kinase, AIM-1 (Aurora and Ipl1-like midbody-associated protein), is crucial for cell division in mammals. It ensures proper cytokinesis, preventing errors like polyploidy and cell death.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Mitosis ensures accurate chromosome segregation, preventing aneuploidy, cell death, and oncogenesis.
- Protein kinases play vital roles in regulating cell division processes.
Purpose of the Study:
- To identify and characterize a novel mammalian protein kinase involved in mitosis.
- To elucidate the function of AIM-1 in chromosome segregation and cytokinesis.
Main Methods:
- Described a putative mammalian protein kinase, AIM-1.
- Analyzed AIM-1 expression during the cell cycle (G2/M phase).
- Investigated AIM-1 localization during anaphase, telophase, and cytokinesis.
- Studied the effects of overexpressing kinase-inactive AIM-1 on cell division.
Main Results:
- AIM-1 message and protein accumulate during G2/M phase.
- AIM-1 localizes to central spindles and the midbody during late stages of mitosis.
- Overexpression of kinase-inactive AIM-1 disrupts cleavage furrow formation and impairs cytokinesis.
- Failed cytokinesis leads to cell polyploidy and subsequent cell death.
Conclusions:
- AIM-1 is essential for the accurate progression of cytokinesis in mammalian cells.
- Disruption of AIM-1 function leads to polyploidy and cell death, highlighting its critical role in cell division fidelity.