The C. elegans Tousled-like kinase contributes to chromosome segregation as a substrate and regulator of the Aurora B kinase

Curr Biol. 2005 May 24;15(10):894-904. doi: 10.1016/j.cub.2005.04.019.

Abstract

Background: The Aurora kinases control multiple aspects of mitosis, among them centrosome maturation, spindle assembly, chromosome segregation, and cytokinesis. Aurora activity is regulated in part by a subset of Aurora substrates that, once phosphorylated, can enhance Aurora kinase activity. Aurora A substrate activators include TPX2 and Ajuba, whereas the only known Aurora B substrate activator is the chromosomal passenger INCENP.

Results: We report that the C. elegans Tousled kinase TLK-1 is a second substrate activator of the Aurora B kinase AIR-2. Tousled kinase (Tlk) expression and activity have been linked to ongoing DNA replication, and Tlk can phosphorylate the chromatin assembly factor Asf. Here, we show that TLK-1 is phosphorylated by AIR-2 during prophase/prometaphase and that phosphorylation increases TLK-1 kinase activity in vitro. Phosphorylated TLK-1 increases AIR-2 kinase activity in a manner that is independent of TLK-1 kinase activity but depends on the presence of ICP-1/INCENP. In vivo, TLK-1 and AIR-2 cooperate to ensure proper mitotic chromosome segregation.

Conclusions: The C. elegans Tousled kinase TLK-1 is a substrate and activator of the Aurora B kinase AIR-2. These results suggest that Tousled kinases have a previously unrecognized role in mitosis and that Aurora B associates with discrete regulatory complexes that may impart distinct substrate specificities and functions to the Aurora B kinase.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aurora Kinase B
  • Blotting, Western
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosome Segregation / physiology*
  • DNA, Complementary / genetics
  • Immunohistochemistry
  • Immunoprecipitation
  • Mitosis / physiology*
  • Phosphorylation
  • Plasmids / genetics
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA Interference
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Analysis, DNA
  • Two-Hybrid System Techniques

Substances

  • Caenorhabditis elegans Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA, Complementary
  • Recombinant Proteins
  • TLK-1 protein, C elegans
  • Aurora Kinase B
  • Protein-Serine-Threonine Kinases
  • air-2 protein, C elegans