title: The tumor suppressor Lats2 is pivotal in Aurora A and Aurora B signaling during mitosis.
abstract: Accurate coordination between chromosome segregation and cytokinesis by various mitotic kinases, such as Aurora, prevent tetraploidization and subsequent tumorigensis. The tumor suppressors Lats1 and Lats2 are serine/threonine kinases that localize to the centrosome and regulate cell cycle progression and apoptosis. In the present study, Aurora A was demonstrated to phosphorylate Lats2 on serine 380 (S380) during mitosis. Immunocytochemical observations revealed that the subcellular localization of Lats2 was distinct during the cell cycle and depended on which site was phosphorylated. Interestingly, the S380-phosphorylated Lats2 protein (pS380) colocalized at the central spindle with Aurora B. Physical interactions were observed between Aurora A, Lats2, Lats1 and Aurora B. The Lats1 kinase was shown to phosphorylate Aurora B. Cells expressing a nonphosphorylated mutant (S380A) of Lats2 caused chromosome missegregation and cytokinesis failure, similar to cells with aberrantly expressed Aurora B. Together, the results suggest that the Aurora A-Lats1/2-Aurora B axis might be a novel pathway that regulates accurate mitotic progression by ensuring the proper mitotic localization of Lats2.
authors.affiliation: Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, Suita City, Osaka, Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Yabuta
authors.forename: Satomi
authors.initials: S
authors.lastname: Mukai
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Okada
authors.forename: Yael
authors.initials: Y
authors.lastname: Aylon
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nojima
mesh_terms: D000818:Animals; D017209:Apoptosis; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002460:Cell Line; D018385:Centrosome / Q000378:metabolism; D020090:Chromosome Segregation; D002875:Chromosomes / Q000378:metabolism; D006801:Humans; D051379:Mice; D008938:Mitosis; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D008941:Spindle Apparatus / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; C092745:LATS1 protein, human; C406449:LATS2 protein, human; C576921:AURKB protein, human; C576918:Aurka protein, mouse; C576924:Aurkb protein, mouse; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases