Insights into the non-mitotic functions of Aurora kinase A: more than just cell division

Cell Mol Life Sci. 2020 Mar;77(6):1031-1047. doi: 10.1007/s00018-019-03310-2. Epub 2019 Sep 27.

Abstract

AURKA is a serine/threonine kinase overexpressed in several cancers. Originally identified as a protein with multifaceted roles during mitosis, improvements in quantitative microscopy uncovered several non-mitotic roles as well. In physiological conditions, AURKA regulates cilia disassembly, neurite extension, cell motility, DNA replication and senescence programs. In cancer-like contexts, AURKA actively promotes DNA repair, it acts as a transcription factor, promotes cell migration and invasion, and it localises at mitochondria to regulate mitochondrial dynamics and ATP production. Here we review the non-mitotic roles of AURKA, and its partners outside of cell division. In addition, we give an insight into how structural data and quantitative fluorescence microscopy allowed to understand AURKA activation and its interaction with new substrates, highlighting future developments in fluorescence microscopy needed to better understand AURKA functions in vivo. Last, we will recapitulate the most significant AURKA inhibitors currently in clinical trials, and we will explore how the non-mitotic roles of the kinase may provide new insights to ameliorate current pharmacological strategies against AURKA overexpression.

Keywords: AURKA; Cell cycle; FRET; Fluorescence microscopy; Non-mitotic roles; Structural data.

Publication types

  • Review

MeSH terms

  • Animals
  • Aurora Kinase A / analysis
  • Aurora Kinase A / antagonists & inhibitors
  • Aurora Kinase A / metabolism*
  • Cell Cycle / drug effects
  • Cell Movement / drug effects
  • Enzyme Activation / drug effects
  • Humans
  • Microscopy, Fluorescence
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondrial Dynamics / drug effects
  • Mitosis / drug effects
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Protein Kinase Inhibitors / pharmacology
  • Substrate Specificity

Substances

  • Protein Kinase Inhibitors
  • Aurora Kinase A