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Large tumor suppressors 1 and 2 regulate Aurora-B through phosphorylation of INCENP to ensure completion of cytokinesis

The tumor suppressor kinases LATS1 and LATS2 (LATS1/2) regulate not only organ size through the Hippo signaling pathway, but also cell-cycle checkpoints and apoptosis via other signaling cascades. We previously reported that LATS1/2 localize to the mitotic apparatus, where they are involved in the p...

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Autores principales: Yabuta, Norikazu, Yoshida, Kaori, Mukai, Satomi, Kato, Yorika, Torigata, Kosuke, Nojima, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971130/
https://www.ncbi.nlm.nih.gov/pubmed/27512725
http://dx.doi.org/10.1016/j.heliyon.2016.e00131
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author Yabuta, Norikazu
Yoshida, Kaori
Mukai, Satomi
Kato, Yorika
Torigata, Kosuke
Nojima, Hiroshi
author_facet Yabuta, Norikazu
Yoshida, Kaori
Mukai, Satomi
Kato, Yorika
Torigata, Kosuke
Nojima, Hiroshi
author_sort Yabuta, Norikazu
collection PubMed
description The tumor suppressor kinases LATS1 and LATS2 (LATS1/2) regulate not only organ size through the Hippo signaling pathway, but also cell-cycle checkpoints and apoptosis via other signaling cascades. We previously reported that LATS1/2 localize to the mitotic apparatus, where they are involved in the phosphorylation and activation of the mitotic kinase Aurora-B; however, the detailed mechanism of LATS1/2 action remains obscure. The activity of Aurora-B is stringently regulated by formation of the chromosomal passenger complex containing the inner centromere protein (INCENP), which leads to appropriate activation of Aurora-B during mitosis and cytokinesis. In this study, we found that LATS1/2 phosphorylated INCENP at S894 in the Thr-Ser-Ser motif. Moreover, the LATS-mediated phosphorylation of S894 was necessary and sufficient for the activation of Aurora-B, which is required for completion of cytokinesis in cells engaged in multipolar division. We propose a novel mechanism for regulation of Aurora-B via INCENP phosphorylation by LATS1/2 during cytokinesis.
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spelling pubmed-49711302016-08-10 Large tumor suppressors 1 and 2 regulate Aurora-B through phosphorylation of INCENP to ensure completion of cytokinesis Yabuta, Norikazu Yoshida, Kaori Mukai, Satomi Kato, Yorika Torigata, Kosuke Nojima, Hiroshi Heliyon Article The tumor suppressor kinases LATS1 and LATS2 (LATS1/2) regulate not only organ size through the Hippo signaling pathway, but also cell-cycle checkpoints and apoptosis via other signaling cascades. We previously reported that LATS1/2 localize to the mitotic apparatus, where they are involved in the phosphorylation and activation of the mitotic kinase Aurora-B; however, the detailed mechanism of LATS1/2 action remains obscure. The activity of Aurora-B is stringently regulated by formation of the chromosomal passenger complex containing the inner centromere protein (INCENP), which leads to appropriate activation of Aurora-B during mitosis and cytokinesis. In this study, we found that LATS1/2 phosphorylated INCENP at S894 in the Thr-Ser-Ser motif. Moreover, the LATS-mediated phosphorylation of S894 was necessary and sufficient for the activation of Aurora-B, which is required for completion of cytokinesis in cells engaged in multipolar division. We propose a novel mechanism for regulation of Aurora-B via INCENP phosphorylation by LATS1/2 during cytokinesis. Elsevier 2016-07-20 /pmc/articles/PMC4971130/ /pubmed/27512725 http://dx.doi.org/10.1016/j.heliyon.2016.e00131 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Yabuta, Norikazu
Yoshida, Kaori
Mukai, Satomi
Kato, Yorika
Torigata, Kosuke
Nojima, Hiroshi
Large tumor suppressors 1 and 2 regulate Aurora-B through phosphorylation of INCENP to ensure completion of cytokinesis
title Large tumor suppressors 1 and 2 regulate Aurora-B through phosphorylation of INCENP to ensure completion of cytokinesis
title_full Large tumor suppressors 1 and 2 regulate Aurora-B through phosphorylation of INCENP to ensure completion of cytokinesis
title_fullStr Large tumor suppressors 1 and 2 regulate Aurora-B through phosphorylation of INCENP to ensure completion of cytokinesis
title_full_unstemmed Large tumor suppressors 1 and 2 regulate Aurora-B through phosphorylation of INCENP to ensure completion of cytokinesis
title_short Large tumor suppressors 1 and 2 regulate Aurora-B through phosphorylation of INCENP to ensure completion of cytokinesis
title_sort large tumor suppressors 1 and 2 regulate aurora-b through phosphorylation of incenp to ensure completion of cytokinesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971130/
https://www.ncbi.nlm.nih.gov/pubmed/27512725
http://dx.doi.org/10.1016/j.heliyon.2016.e00131
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