ATM-mediated Mad1 Serine 214 phosphorylation regulates Mad1 dimerization and the spindle assembly checkpoint

Chunying Yang, Jianwei Hao, Dejuan Kong, Xiaoli Cui, Wei Zhang, Haibo Wang, Xiaojing Guo, Shumei Ma, Xiaodong Liu, Peiyu Pu, Bo Xu

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The spindle assembly checkpoint (SAC), which blocks anaphase onset until all chromosomes have bi-oriented, is one of the key selfmonitoring systems of the eukaryotic cell cycle for genome stability. The mitotic arrest-deficient protein 1 (Mad1), a critical component of the SAC, is hyperphosphorylated in mitosis. However, the kinases responsible for Mad1 phosphorylation and its functional significance are not fully understood. Here we report that Mad1 is phosphorylated on Serine 214 by the Ataxia-Telangiectasia Mutated (ATM) kinase, a critical DNA damage response protein also activated in mitosis and required for the SAC. We demonstrate that Mad1 Serine 214 phosphorylation promotes the formation of homodimerization of Mad1 and its heterodimerization with Mad2. Further we show that Mad1 Serine 214 phosphorylation contribute to activation of the SAC and the maintenance of chromosomal stability. Together, these findings reveal an important role of ATMmediated Mad1 Serine 214 phosphorylation in mitosis.

Original languageEnglish (US)
Article numberbgu087
Pages (from-to)2007-2013
Number of pages7
JournalCarcinogenesis
Volume35
Issue number9
DOIs
StatePublished - Sep 2014

ASJC Scopus subject areas

  • Cancer Research

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