v-Src causes delocalization of Mklp1, Aurora B, and INCENP from the spindle midzone during cytokinesis failure

详细信息    查看全文

• 作者：Shuhei Soeda^a ; Yuji Nakayama^a ; ^b ; ^{nakayama@mb.kyoto-phu.ac.jp} ; Takuya Honda^a ; Azumi Aoki^a ; Naoki Tamura^a ; Kohei Abe^a ; Yasunori Fukumoto^a ; Naoto Yamaguchi^a ; ^{nyama@faculty.chiba-u.jp}
• 关键词：v-Src ; Aurora B ; Mklp1 ; INCENP ; Cytokinesis ; Binucleation
• 刊名：Experimental Cell Research
• 出版年：2013
• 出版时间：10 June, 2013
• 年：2013
• 卷：319
• 期：10
• 页码：1382-1397
• 全文大小：10624 K

文摘

Src-family tyrosine kinases are aberrantly activated in cancers, and this activation is associated with malignant tumor progression. v-Src, encoded by the v-src transforming gene of the Rous sarcoma virus, is a mutant variant of the cellular proto-oncogene c-Src. Although investigations with temperature sensitive mutants of v-Src have shown that v-Src induces many oncogenic processes, the effects on cell division are unknown. Here, we show that v-Src inhibits cellular proliferation of HCT116, HeLa S3 and NIH3T3 cells. Flow cytometry analysis indicated that inducible expression of v-Src results in an accumulation of 4N cells. Time-lapse analysis revealed that binucleation is induced through the inhibition of cytokinesis, a final step of cell division. The localization of Mklp1, which is essential for cytokinesis, to the spindle midzone is inhibited in v-Src-expressing cells. Intriguingly, Aurora B, which regulates Mklp1 localization at the midzone, is delocalized from the spindle midzone and the midbody but not from the metaphase chromosomes upon v-Src expression. Mklp2, which is responsible for the relocation of Aurora B from the metaphase chromosomes to the spindle midzone, is also lost from the spindle midzone. These results suggest that v-Src inhibits cytokinesis through the delocalization of Mklp1 and Aurora B from the spindle midzone, resulting in binucleation.