The C. elegans Tousled-like kinase contributes to chromosome segregation as a substrate and regulator of the Aurora B kinase.
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.
Han
Zhenbo
Z
Department of Molecular Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Riefler
Gary M
GM
Saam
Jennifer R
JR
Mango
Susan E
SE
Schumacher
Jill M
JM
D000818:Animals; D064107:Aurora Kinase B; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000378:metabolism / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D020090:Chromosome Segregation / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008938:Mitosis / Q000502:physiology*; D010766:Phosphorylation; D010957:Plasmids / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D020798:Two-Hybrid System Techniques
D029742:Caenorhabditis elegans Proteins; D002868:Chromosomal Proteins, Non-Histone; D018076:DNA, Complementary; D011994:Recombinant Proteins; C498928:TLK-1 protein, C elegans; D064107:Aurora Kinase B; D017346:Protein Serine-Threonine Kinases; C491506:air-2 protein, C elegans