Aurora A activation in mitosis promoted by BuGZ

J Cell Biol. 2018 Jan 2;217(1):107-116. doi: 10.1083/jcb.201706103. Epub 2017 Oct 26.

Abstract

Protein phase separation or coacervation has emerged as a potential mechanism to regulate biological functions. We have shown that coacervation of a mostly unstructured protein, BuGZ, promotes assembly of spindle and its matrix. BuGZ in the spindle matrix binds and concentrates tubulin to promote microtubule (MT) assembly. It remains unclear, however, whether BuGZ could regulate additional proteins to promote spindle assembly. In this study, we report that BuGZ promotes Aurora A (AurA) activation in vitro. Depletion of BuGZ in cells reduces the amount of phosphorylated AurA on spindle MTs. BuGZ also enhances MCAK phosphorylation. The two zinc fingers in BuGZ directly bind to the kinase domain of AurA, which allows AurA to incorporate into the coacervates formed by BuGZ in vitro. Importantly, mutant BuGZ that disrupts the coacervation activity in vitro fails to promote AurA phosphorylation in Xenopus laevis egg extracts. These results suggest that BuGZ coacervation promotes AurA activation in mitosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aurora Kinase A / antagonists & inhibitors
  • Aurora Kinase A / metabolism*
  • Azepines / pharmacology
  • Cell Cycle Proteins / genetics
  • Cell Line, Tumor
  • HeLa Cells
  • Humans
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Microtubule-Associated Proteins / physiology*
  • Microtubules / metabolism
  • Mitosis / physiology*
  • Nuclear Proteins / genetics
  • Phosphorylation
  • Protein Binding
  • Protein Domains
  • Pyrimidines / pharmacology
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Spindle Apparatus / metabolism*
  • Xenopus laevis / embryology

Substances

  • Azepines
  • Cell Cycle Proteins
  • MLN 8237
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • Pyrimidines
  • RNA, Small Interfering
  • TPX2 protein, human
  • ZNF207 protein, human
  • AURKA protein, human
  • Aurora Kinase A