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

Norikazu Yabuta; Kaori Yoshida; Satomi Mukai; Yorika Kato; Kosuke Torigata; Hiroshi Nojima

doi:10.1016/j.heliyon.2016.e00131

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

Heliyon. 2016 Jul 20;2(7):e00131. doi: 10.1016/j.heliyon.2016.e00131. eCollection 2016 Jul.

Authors

Norikazu Yabuta¹, Kaori Yoshida¹, Satomi Mukai¹, Yorika Kato¹, Kosuke Torigata¹, Hiroshi Nojima¹

Affiliation

¹ Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita City, Osaka 565-0871, Japan.

Abstract

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.

Keywords: Cell biology.