An Afg2/Spaf-related Cdc48-like AAA ATPase regulates the stability and activity of the C. elegans Aurora B kinase AIR-2.
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.
Department of Genetics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Todd R
TR
Heallen
Henry P
HP
Adams
Tokiko
T
Furuta
Koen J
KJ
Verbrugghe
Jill M
JM
Schumacher
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000483:Alleles; D019943:Amino Acid Substitution; D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008938:Mitosis; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D011994:Recombinant Proteins / Q000378:metabolism; D013696:Temperature; D000074405:Valosin Containing Protein
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D011994:Recombinant Proteins; D005982:Glutathione Transferase; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; C491506:air-2 protein, C elegans; D000251:Adenosine Triphosphatases; C406634:spermatogenesis associated factor; D000074405:Valosin Containing Protein; D008239:Lysine