Mio depletion links mTOR regulation to Aurora A and Plk1 activation at mitotic centrosomes

Melpomeni Platani, Laura Trinkle-Mulcahy, Michael Porter, Arockia Arulanandam, William C Earnshaw

Research output: Contribution to journalArticlepeer-review

Abstract

Coordination of cell growth and proliferation in response to nutrient supply is mediated by mammalian target of rapamycin (mTOR) signaling. In this study, we report that Mio, a highly conserved member of the SEACAT/GATOR2 complex necessary for the activation of mTORC1 kinase, plays a critical role in mitotic spindle formation and subsequent chromosome segregation by regulating the proper concentration of active key mitotic kinases Plk1 and Aurora A at centrosomes and spindle poles. Mio-depleted cells showed reduced activation of Plk1 and Aurora A kinase at spindle poles and an impaired localization of MCAK and HURP, two key regulators of mitotic spindle formation and known substrates of Aurora A kinase, resulting in spindle assembly and cytokinesis defects. Our results indicate that a major function of Mio in mitosis is to regulate the activation/deactivation of Plk1 and Aurora A, possibly by linking them to mTOR signaling in a pathway to promote faithful mitotic progression.

Original languageEnglish
Pages (from-to)45-62
Number of pages18
JournalJournal of Cell Biology
Volume210
Issue number1
DOIs
Publication statusPublished - 6 Jul 2015

Keywords

  • Amino Acid Sequence
  • Aurora Kinase A
  • Cell Cycle Proteins
  • Centrosome
  • Enzyme Activation
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • Kinesin
  • Mitosis
  • Molecular Sequence Data
  • Neoplasm Proteins
  • Nuclear Pore Complex Proteins
  • Protein Structure, Tertiary
  • Protein Transport
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins
  • Spindle Apparatus
  • TOR Serine-Threonine Kinases

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