Asano Eri, Hasegawa Hitoki, Hyodo Toshinori, Ito Satoko, Maeda Masao, Chen Dan, Takahashi Masahide, Hamaguchi Michinari, Senga Takeshi
a Division of Cancer Biology ; Nagoya University Graduate School of Medicine ; Nagoya , Japan.
Cell Cycle. 2014;13(17):2744-51. doi: 10.4161/15384101.2015.945840.
The centralspindlin complex, which is composed of MKLP1 and MgcRacGAP, is one of the crucial factors involved in cytokinesis initiation. Centralspindlin is localized at the middle of the central spindle during anaphase and then concentrates at the midbody to control abscission. A number of proteins that associate with centralspindlin have been identified. These associating factors regulate furrowing and abscission in coordination with centralspindlin. A recent study identified a novel centralspindlin partner, called Nessun Dorma, which is essential for germ cell cytokinesis in Drosophila melanogaster. SHCBP1 is a human ortholog of Nessun Dorma that associates with human centralspindlin. In this report, we analyzed the interaction of SHCBP1 with centralspindlin in detail and determined the regions that are required for the interaction. In addition, we demonstrate that the central region is necessary for the SHCBP1 dimerization. Both MgcRacGAP and MKLP1 are degraded once cells exit mitosis. Similarly, endogenous and exogenous SHCBP1 were degraded with mitosis progression. Interestingly, SHCBP1 expression was significantly reduced in the absence of centralspindlin, whereas centralspindlin expression was not affected by SHCBP1 knockdown. Finally, we demonstrate that SHCBP1 depletion promotes midbody structure disruption and inhibits abscission, a final stage of cytokinesis. Our study gives novel insight into the role of SHCBP in cytokinesis completion.
由MKLP1和MgcRacGAP组成的中央纺锤体复合物是参与胞质分裂起始的关键因素之一。中央纺锤体复合物在后期定位于中央纺锤体的中部，然后集中在中体以控制细胞分裂。已经鉴定出许多与中央纺锤体复合物相关的蛋白质。这些相关因子与中央纺锤体复合物协同调节沟裂和细胞分裂。最近的一项研究鉴定出一种名为“Nessun Dorma”的新型中央纺锤体复合物伴侣，它对黑腹果蝇生殖细胞的胞质分裂至关重要。SHCBP1是“Nessun Dorma”在人类中的同源物，与人类中央纺锤体复合物相关。在本报告中，我们详细分析了SHCBP1与中央纺锤体复合物的相互作用，并确定了相互作用所需的区域。此外，我们证明中央区域对于SHCBP1二聚化是必需的。一旦细胞退出有丝分裂，MgcRacGAP和MKLP1都会降解。同样，内源性和外源性SHCBP1也会随着有丝分裂进程而降解。有趣的是，在没有中央纺锤体复合物的情况下，SHCBP1的表达显著降低，而中央纺锤体复合物的表达不受SHCBP1敲低的影响。最后，我们证明SHCBP1的缺失会促进中体结构破坏并抑制细胞分裂的最后阶段——细胞脱离。我们的研究为SHCBP在胞质分裂完成中的作用提供了新的见解。
