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Publication : Functional involvement of human discs large tumor suppressor in cytokinesis.

First Author  Unno K Year  2008
Journal  Exp Cell Res Volume  314
Issue  17 Pages  3118-29
PubMed ID  18760273 Mgi Jnum  J:141197
Mgi Id  MGI:3817395 Doi  10.1016/j.yexcr.2008.07.032
Citation  Unno K, et al. (2008) Functional involvement of human discs large tumor suppressor in cytokinesis. Exp Cell Res 314(17):3118-29
abstractText  Cytokinesis is the final step of cell division that completes the separation of two daughter cells. We found that the human discs large (hDlg) tumor suppressor homologue is functionally involved in cytokinesis. The guanylate kinase (GUK) domain of hDlg mediates the localization of hDlg to the midbody during cytokinesis, and over-expression of the GUK domain in U2OS and HeLa cells impaired cytokinesis. Mouse embryonic fibroblasts (MEFs) derived from dlg mutant mice contained an increased number of multinucleated cells and showed reduced proliferation in culture. A kinesin-like motor protein, GAKIN, which binds directly to the GUK domain of hDlg, exhibited a similar intracellular distribution pattern with hDlg throughout mitosis and localized to the midbody during cytokinesis. However, the targeting of hDlg and GAKIN to the midbody appeared to be independent of each other. The midbody localization of GAKIN required its functional kinesin-motor domain. Treatment of cells with the siRNA specific for hDlg and GAKIN caused formation of multinucleated cells and delayed cytokinesis. Together, these results suggest that hDlg and GAKIN play functional roles in the maintenance of midbody architecture during cytokinesis.
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