Functional involvement of human discs large tumor suppressor in cytokinesis.
Functional involvement of human discs large tumor suppressor in cytokinesis.
复制标题
人类椎间盘大肿瘤抑制因子在胞质分裂中的功能参与。
DOI：
10.1016/j.yexcr.2008.07.032
复制
发表时间：
2008
影响因子：
3.7
通讯作者：
Chishti,AtharH
中科院分区：
文献类型：
--
作者：
Unno,Kenji;Hanada,Toshihiko;Chishti,AtharH
胞质分裂是细胞分裂的最后一步，完成两个子细胞的分离。我们发现人类椎间盘大（hDlg）肿瘤抑制同源物在功能上参与胞质分裂。鸟苷酸激酶（GUK）结构域的hDlg介导的定位hDlg的中间体在胞质分裂，和过表达的GUK结构域在U2 OS和HeLa细胞受损的胞质分裂。来自dlg突变小鼠的小鼠胚胎成纤维细胞（MEFs）含有增加数量的多核细胞，并在培养中表现出增殖减少。驱动蛋白样马达蛋白，GAKIN，它直接结合到GUK结构域的hDlg，表现出类似的细胞内分布模式与hDlg在整个有丝分裂和定位到中间体在胞质分裂。然而，hDlg和GAKIN对中间体的靶向似乎彼此独立。GAKIN的中体定位需要其功能性驱动蛋白-运动域。用hDlg和GAKIN特异性的SiRNA处理细胞会导致多核细胞的形成并延迟胞质分裂。总之，这些结果表明hDlg和GAKIN在胞质分裂期间维持中间体结构中发挥功能作用。
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.