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PMID:18854144

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Citation

Heallen, TR, Adams, HP, Furuta, T, Verbrugghe, KJ and Schumacher, JM (2008) An Afg2/Spaf-related Cdc48-like AAA ATPase regulates the stability and activity of the C. elegans Aurora B kinase AIR-2. Dev. Cell 15:603-16

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.

Links

PubMed PMC2582393 Online version:10.1016/j.devcel.2008.08.005

Keywords

Adenosine Triphosphatases/genetics; Adenosine Triphosphatases/metabolism; Alleles; Amino Acid Substitution; Animals; 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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:G5EDL3

involved_in

GO:0006468: protein phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:G5EDL3

enables

GO:0004672: protein kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:AIR2

involved_in

GO:0006468: protein phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:AIR2

enables

GO:0004672: protein kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:AIR2

enables

GO:0051117: ATPase binding

ECO:0000353: physical interaction evidence used in manual assertion

WB:WBGene00010562

F

Seeded From UniProt

complete

CAEEL:TERA1

enables

GO:0016887: ATP hydrolysis activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:AFG2H

enables

GO:0019901: protein kinase binding

ECO:0000353: physical interaction evidence used in manual assertion

WB:WBGene00000099

F

Seeded From UniProt

complete

CAEEL:AFG2H

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:AFG2H

involved_in

GO:0006469: negative regulation of protein kinase activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:AFG2H

enables

GO:0016887: ATP hydrolysis activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

CAEEL:AFG2H

enables

GO:0004860: protein kinase inhibitor activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(UniProtKB:O01427)

Seeded From UniProt

complete


See also

References

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