title: v-Src causes delocalization of Mklp1, Aurora B, and INCENP from the spindle midzone during cytokinesis failure.
abstract: 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.
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Soeda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Takuya
authors.initials: T
authors.lastname: Honda
authors.forename: Azumi
authors.initials: A
authors.lastname: Aoki
authors.forename: Naoki
authors.initials: N
authors.lastname: Tamura
authors.forename: Kohei
authors.initials: K
authors.lastname: Abe
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Fukumoto
authors.forename: Naoto
authors.initials: N
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002467:Cell Nucleus / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism; D048749:Cytokinesis; D005434:Flow Cytometry; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D008677:Metaphase; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008940:Mitotic Index; D041681:NIH 3T3 Cells; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D000090063:Proto-Oncogene Mas; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*; D059008:Time-Lapse Imaging
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C083767:INCENP protein, human; C410089:KIF20A protein, human; C092935:KIF23 protein, human; C000715470:MAS1 protein, human; D008869:Microtubule-Associated Proteins; D000090063:Proto-Oncogene Mas; D015688:Oncogene Protein pp60(v-src); C576921:AURKB protein, human; C576924:Aurkb protein, mouse; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D016547:Kinesins