MST1 Limits the Kinase Activity of Aurora B to Promote Stable Kinetochore-Microtubule Attachment

Hyun Jung Oh, Mi Ju Kim, Su Jung Song, Tackhoon Kim, Dongjun Lee, Seung Hae Kwon, Eui Ju Choi, Dae Sik Lim

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

The establishment and maintenance of proper attachment of kinetochores to microtubules are required to prevent chromosome missegregation and consequent chromosomal instability and tumorigenesis. Although MST1 (mammalian sterile 20-like kinase 1) has been implicated in many aspects of cell cycle regulation and tumor suppression [1], its precise mechanism of action has remained largely unknown. We now show that MST1 promotes accurate kinetochore-microtubule attachment by modulating the kinase activity of Aurora B. HeLa cells depleted of MST1 failed to develop stable end-on kinetochore-microtubule attachment, giving rise to unaligned mitotic chromosomes. The misaligned chromosomes activated the Mad2- and BubR1-dependent spindle checkpoint response, resulting in a delay in anaphase onset. The kinase activity of Aurora B, which promotes destabilization of kinetochore-microtubule attachment [2-4], was increased in cells depleted of MST1 or NDR1, a downstream kinase of MST1. MST1 and NDR1 associated with Aurora B. Moreover, MST1 directly phosphorylated Aurora B and inhibited its kinase activity in vitro. Depletion of Aurora B restored the stability of kinetochore-microtubule attachment in cells depleted of MST1 or NDR1. MST1 is thus a key regulator of Aurora B activity that ensures mitotic chromosome congression and accurate chromosome segregation.

Original languageEnglish
Pages (from-to)416-422
Number of pages7
JournalCurrent Biology
Volume20
Issue number5
DOIs
Publication statusPublished - 2010 Mar 9

Bibliographical note

Funding Information:
We thank R.H. Medema for GFP-H2B cDNA and E. Nigg for human Aurora B cDNA. This study was supported by the 21st Century Frontier Functional Human Genome Project of Korea Science and Engineering Foundation, the Korea National Cancer Center Control Program, the National Research Laboratory Program of Korea, and the Nuclear Research Program of Korea.

Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.

Keywords

  • CELLBIO

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences

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