期刊
CELLULAR SIGNALLING
卷 30, 期 -, 页码 19-29出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2016.11.014
关键词
v-Src; Tetraploidy checkpoint; Multipolar spindle; YAP
类别
资金
- Japan Society for the Promotion of Science [16K08253, 25460076, 26460081, 26870701]
- Promotion and Mutual Aid Corporation for Private Schools of Japan (Kyoto Pharmaceutical University)
- Promotion and Mutual Aid Corporation for Private Schools of Japan (Chiba University)
- Kyoto Pharmaceutical University Fund for the Promotion of Scientific Research
- MEXT-Supported Program for the Strategic Research Foundation at Private Universities [S1311035]
- Grants-in-Aid for Scientific Research [26460081, 16K08253, 26870701, 15K07922] Funding Source: KAKEN
The protein-tyrosine kinase, c-Src, is involved in a variety of signaling events, including cell division. We have reported that v-Src, which is a mutant variant of the cellular proto-oncogene, c-Src, causes delocalization of Aurora B kinase, resulting in a furrow regression in cytokinesis and the generation of multinucleated cells. However, the effect of v-Src on mitotic spindle formation is unknown. Here we show that v-Src-expressing HCT116 and NIH3T3 cells undergo abnormal cell division, in which cells separate into more than two cells. Upon v-Src expression, the proportion of multinucleated cells is increased in a time-dependent manner. Flow cytometry analysis revealed that v-Src increases the number of cells having a >= 4 N DNA content. Microscopic analysis showed that v-Src induces the formation of multipolar spindles with excess centrosomes. These results suggest that vSrc induces multipolar spindle formation by generating multinucleated cells. Tetraploidy activates the tetraploidy checkpoint, leading to a cell cycle arrest of tetraploid cells at the G1 phase, in which the nuclear exclusion of the transcription co-activator YAP plays a critical role. In multinucleated cells that are induced by cytochalasin B and the Plkl inhibitor, YAP is excluded from the nucleus. However, v-Src prevents this nuclear exclusion of YAP through a decrease in the phosphorylation of YAP at Ser127 in multinucleated cells. Furthermore, v-Src decreases the expression level of p53, which also plays a critical role in the cell cycle arrest of tetraploid cells. These results suggest that v-Src promotes abnormal spindle formation in at least two ways: generation of multinucleated cells and a weakening of the tetraploidy checkpoint. (C) 2016 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据