An Afg2/Spaf-related Cdc48-like AAA ATPase regulates the stability and activity of the C. elegans Aurora B kinase AIR-2

Dev Cell. 2008 Oct;15(4):603-16. doi: 10.1016/j.devcel.2008.08.005.

Abstract

The Aurora B kinase is the enzymatic core of the chromosomal passenger complex, which is a critical regulator of mitosis. To identify novel regulators of Aurora B, we performed a genome-wide screen for suppressors of a temperature-sensitive lethal allele of the C. elegans Aurora B kinase AIR-2. This screen uncovered a member of the Afg2/Spaf subfamily of Cdc48-like AAA ATPases as an essential inhibitor of AIR-2 stability and activity. Depletion of CDC-48.3 restores viability to air-2 mutant embryos and leads to abnormally high AIR-2 levels at the late telophase/G1 transition. Furthermore, CDC-48.3 binds directly to AIR-2 and inhibits its kinase activity from metaphase through telophase. While canonical p97/Cdc48 proteins have been assigned contradictory roles in the regulation of Aurora B, our results identify a member of the Afg2/Spaf AAA ATPases as a critical in vivo inhibitor of this kinase during embryonic development.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Alleles
  • Amino Acid Substitution
  • Animals
  • Aurora Kinase B
  • Aurora Kinases
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / antagonists & inhibitors*
  • Caenorhabditis elegans Proteins / genetics
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Glutathione Transferase / metabolism
  • Lysine / metabolism
  • Mitosis
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein-Serine-Threonine Kinases / genetics
  • RNA Interference
  • Recombinant Proteins / metabolism
  • Temperature
  • Valosin Containing Protein

Substances

  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • Recombinant Proteins
  • Glutathione Transferase
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • air-2 protein, C elegans
  • Adenosine Triphosphatases
  • spermatogenesis associated factor
  • Valosin Containing Protein
  • Lysine