The UBXN-2/p37/p47 Adaptors of CDC-48/p97 Regulate Mitosis by Limiting the Centrosomal Recruitment of Aurora A

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2013 May 8

PMID 23649807

Citations 16

Authors

Elsa Kress

Francoise Schwager

Rene Holtackers

Jonas Seiler

Francois Prodon

Esther Zanin

Annika Eiteneuer

Mika Toya

Asako Sugimoto

Hemmo Meyer

Patrick Meraldi

Monica Gotta

Affiliations

Soon will be listed here.

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.

Citing Articles

Asymmetry in centrosome maturation revealed through AIR-1 dynamics in the early Caenorhabditis elegans embryo.

Plourde S, Kravtsova N, Dawes A Sci Rep. 2025; 15(1):8667.

PMID: 40082489 PMC: 11906807. DOI: 10.1038/s41598-025-86548-0.

Identification of Genes Associated with Familial Focal Segmental Glomerulosclerosis Through Transcriptomics and In Silico Analysis, Including , , and .

Mahmoud A, Alhamidi R, Ilce B, Hamad A, Ali N, Mahasneh A Int J Mol Sci. 2024; 25(21).

PMID: 39519211 PMC: 11546068. DOI: 10.3390/ijms252111659.

Valosin containing protein (VCP): initiator, modifier, and potential drug target for neurodegenerative diseases.

Chu S, Xie X, Payan C, Stochaj U Mol Neurodegener. 2023; 18(1):52.

PMID: 37545006 PMC: 10405438. DOI: 10.1186/s13024-023-00639-y.

EMC3 regulates mesenchymal cell survival via control of the mitotic spindle assembly.

Tang X, Wei W, Snowball J, Nakayasu E, Bell S, Ansong C iScience. 2023; 26(1):105667.

PMID: 36624844 PMC: 9823123. DOI: 10.1016/j.isci.2022.105667.

The phosphorylation and dephosphorylation switch of VCP/p97 regulates the architecture of centrosome and spindle.

Zhu K, Cai Y, Si X, Ye Z, Gao Y, Liu C Cell Death Differ. 2022; 29(10):2070-2088.

PMID: 35430615 PMC: 9525716. DOI: 10.1038/s41418-022-01000-4.

References

Hannak E, Kirkham M, Hyman A, Oegema K . Aurora-A kinase is required for centrosome maturation in Caenorhabditis elegans. J Cell Biol. 2001; 155(7):1109-16. PMC: 2199344. DOI: 10.1083/jcb.200108051. View

Aratyn Y, Schaus T, Taylor E, Borisy G . Intrinsic dynamic behavior of fascin in filopodia. Mol Biol Cell. 2007; 18(10):3928-40. PMC: 1995713. DOI: 10.1091/mbc.e07-04-0346. View

DeBella L, Hayashi A, Rose L . LET-711, the Caenorhabditis elegans NOT1 ortholog, is required for spindle positioning and regulation of microtubule length in embryos. Mol Biol Cell. 2006; 17(11):4911-24. PMC: 1635396. DOI: 10.1091/mbc.e06-02-0107. View

Kaneko Y, Tamura K, Totsukawa G, Kondo H . Phosphorylation of p37 is important for Golgi disassembly at mitosis. Biochem Biophys Res Commun. 2010; 402(1):37-41. DOI: 10.1016/j.bbrc.2010.09.097. View

Uchiyama K, Kondo H . p97/p47-Mediated biogenesis of Golgi and ER. J Biochem. 2005; 137(2):115-9. DOI: 10.1093/jb/mvi028. View

Mains P . Localization of the mei-1 gene product of Caenorhaditis elegans, a meiotic-specific spindle component. J Cell Biol. 1994; 126(1):199-209. PMC: 2120096. DOI: 10.1083/jcb.126.1.199. View

Kloppsteck P, Ewens C, Forster A, Zhang X, Freemont P . Regulation of p97 in the ubiquitin-proteasome system by the UBX protein-family. Biochim Biophys Acta. 2011; 1823(1):125-9. DOI: 10.1016/j.bbamcr.2011.09.006. View

Sasagawa Y, Yamanaka K, Saito-Sasagawa Y, Ogura T . Caenorhabditis elegans UBX cofactors for CDC-48/p97 control spermatogenesis. Genes Cells. 2010; 15(12):1201-15. DOI: 10.1111/j.1365-2443.2010.01454.x. View

Cheng Y, Chen R . The AAA-ATPase Cdc48 and cofactor Shp1 promote chromosome bi-orientation by balancing Aurora B activity. J Cell Sci. 2010; 123(Pt 12):2025-34. DOI: 10.1242/jcs.066043. View

10.

Colanzi A, Suetterlin C, Malhotra V . Cell-cycle-specific Golgi fragmentation: how and why?. Curr Opin Cell Biol. 2003; 15(4):462-7. DOI: 10.1016/s0955-0674(03)00067-x. View

11.

Santaguida S, Vernieri C, Villa F, Ciliberto A, Musacchio A . Evidence that Aurora B is implicated in spindle checkpoint signalling independently of error correction. EMBO J. 2011; 30(8):1508-19. PMC: 3102279. DOI: 10.1038/emboj.2011.70. View

12.

Franz A, Orth M, Pirson P, Sonneville R, Blow J, Gartner A . CDC-48/p97 coordinates CDT-1 degradation with GINS chromatin dissociation to ensure faithful DNA replication. Mol Cell. 2011; 44(1):85-96. PMC: 3428722. DOI: 10.1016/j.molcel.2011.08.028. View

13.

Srayko M, Quintin S, Schwager A, Hyman A . Caenorhabditis elegans TAC-1 and ZYG-9 form a complex that is essential for long astral and spindle microtubules. Curr Biol. 2003; 13(17):1506-11. DOI: 10.1016/s0960-9822(03)00597-9. View

14.

Persico A, Cervigni R, Barretta M, Corda D, Colanzi A . Golgi partitioning controls mitotic entry through Aurora-A kinase. Mol Biol Cell. 2010; 21(21):3708-21. PMC: 2965687. DOI: 10.1091/mbc.E10-03-0243. View

15.

Bastiaens P, Pepperkok R . Observing proteins in their natural habitat: the living cell. Trends Biochem Sci. 2000; 25(12):631-7. DOI: 10.1016/s0968-0004(00)01714-x. View

16.

Steigemann P, Wurzenberger C, Schmitz M, Held M, Guizetti J, Maar S . Aurora B-mediated abscission checkpoint protects against tetraploidization. Cell. 2009; 136(3):473-84. DOI: 10.1016/j.cell.2008.12.020. View

17.

Jaensch S, Decker M, Hyman A, Myers E . Automated tracking and analysis of centrosomes in early Caenorhabditis elegans embryos. Bioinformatics. 2010; 26(12):i13-20. PMC: 2881375. DOI: 10.1093/bioinformatics/btq190. View

18.

Gonczy P, Bellanger J, Kirkham M, Pozniakowski A, Baumer K, Phillips J . zyg-8, a gene required for spindle positioning in C. elegans, encodes a doublecortin-related kinase that promotes microtubule assembly. Dev Cell. 2001; 1(3):363-75. DOI: 10.1016/s1534-5807(01)00046-6. View

19.

OConnell K, MAXWELL K, White J . The spd-2 gene is required for polarization of the anteroposterior axis and formation of the sperm asters in the Caenorhabditis elegans zygote. Dev Biol. 2000; 222(1):55-70. DOI: 10.1006/dbio.2000.9714. View

20.

Song M, Aravind L, Muller-Reichert T, OConnell K . The conserved protein SZY-20 opposes the Plk4-related kinase ZYG-1 to limit centrosome size. Dev Cell. 2008; 15(6):901-12. PMC: 2829447. DOI: 10.1016/j.devcel.2008.09.018. View