The UBXN-2/p37/p47 adaptors of CDC-48/p97 regulate mitosis by limiting the centrosomal recruitment of Aurora A

Elsa Kress; Françoise Schwager; René Holtackers; Jonas Seiler; François Prodon; Esther Zanin; Annika Eiteneuer; Mika Toya; Asako Sugimoto; Hemmo Meyer; Patrick Meraldi; Monica Gotta

doi:10.1083/jcb.201209107

The UBXN-2/p37/p47 adaptors of CDC-48/p97 regulate mitosis by limiting the centrosomal recruitment of Aurora A

J Cell Biol. 2013 May 13;201(4):559-75. doi: 10.1083/jcb.201209107. Epub 2013 May 6.

Authors

Elsa Kress¹, Françoise Schwager, René Holtackers, Jonas Seiler, François Prodon, Esther Zanin, Annika Eiteneuer, Mika Toya, Asako Sugimoto, Hemmo Meyer, Patrick Meraldi, Monica Gotta

Affiliation

¹ Department of Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.

Abstract

Coordination of cell cycle events in space and time is crucial to achieve a successful cell division. Here, we demonstrate that UBXN-2, a substrate adaptor of the AAA ATPase Cdc48/p97, is required to coordinate centrosome maturation timing with mitosis. In UBXN-2-depleted Caenorhabditis elegans embryos, centrosomes recruited more AIR-1 (Aurora A), matured precociously, and alignment of the mitotic spindle with the axis of polarity was impaired. UBXN-2 and CDC-48 coimmunoprecipitated with AIR-1 and the spindle alignment defect was partially rescued by co-depleting AIR-1, indicating that UBXN-2 controls these processes via AIR-1. Similarly, depletion in human cells of the UBXN-2 orthologues p37/p47 resulted in an accumulation of Aurora A at centrosomes and a delay in centrosome separation. The latter defect was also rescued by inhibiting Aurora A. We therefore postulate that the role of this adaptor in cell cycle regulation is conserved.

Publication types

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

MeSH terms

Adaptor Proteins, Signal Transducing / metabolism*
Adaptor Proteins, Signal Transducing / physiology
Adenosine Triphosphatases / metabolism*
Animals
Aurora Kinase A
Aurora Kinases
Caenorhabditis elegans / cytology
Caenorhabditis elegans / genetics
Caenorhabditis elegans Proteins / metabolism*
Caenorhabditis elegans Proteins / physiology
Cell Cycle
Cell Cycle Proteins / metabolism*
Cell Line
Centrosome / metabolism*
Gene Expression Regulation, Developmental
Gene Expression Regulation, Enzymologic
Green Fluorescent Proteins / metabolism
Humans
Mitosis*
Protein Serine-Threonine Kinases / metabolism*
RNA Interference
Valosin Containing Protein

Substances

Adaptor Proteins, Signal Transducing
Caenorhabditis elegans Proteins
Cell Cycle Proteins
UBXN-2 protein, C elegans
p37 protein, human
Green Fluorescent Proteins
Aurora Kinase A
Aurora Kinases
Protein Serine-Threonine Kinases
air-1 protein, C elegans
Adenosine Triphosphatases
Valosin Containing Protein