Functional involvement of human discs large tumor suppressor in cytokinesis

Kenji Unno, Toshihiko Hanada, Athar H. Chishti*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3118-3129
Number of pages12
JournalExperimental Cell Research
Volume314
Issue number17
DOIs
StatePublished - Oct 15 2008

Keywords

  • Cytokinesis
  • Fibroblasts
  • GAKIN
  • HeLa cells
  • MAGUK
  • Midbody
  • hDlg

ASJC Scopus subject areas

  • Cell Biology

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