Therapeutic potential of mitotic interaction between the nucleoporin Tpr and aurora kinase A

Cell Cycle
Akiko KobayashiRichard W Wong

Abstract

Spindle poles are defined by centrosomes; therefore, an abnormal number or defective structural organization of centrosomes can lead to loss of spindle bipolarity and genetic integrity. Previously, we showed that Tpr (translocated promoter region), a component of the nuclear pore complex (NPC), interacts with Mad1 and dynein to promote proper chromosome segregation during mitosis. Tpr also associates with p53 to induce autophagy. Here, we report that Tpr depletion induces mitotic catastrophe and enhances the rate of tetraploidy and polyploidy. Mechanistically, Tpr interacts, via its central domain, with Aurora A but not Aurora B kinase. In Tpr-depleted cells, the expression levels, centrosomal localization and phosphorylation of Aurora A were all reduced. Surprisingly, an Aurora A inhibitor, Alisertib (MLN8237), also disrupted centrosomal localization of Tpr and induced mitotic catastrophe and cell death in a time- and dose-dependent manner. Strikingly, over-expression of Aurora A disrupted Tpr centrosomal localization only in cells with supernumerary centrosomes but not in bipolar cells. Our results highlight the mutual regulation between Tpr and Aurora A and further confirm the importance of nucleoporin function in spindle po...Continue Reading

References

Feb 13, 2002·The Journal of Cell Biology·Phyllis FrosstLarry Gerace
Oct 29, 2003·Molecular Cell·Richard BaylissElena Conti
Apr 13, 2004·Oncogene·Maria CastedoGuido Kroemer
Oct 8, 2004·The Journal of Biological Chemistry·Qiyuan LiuJin Q Cheng
Jun 17, 2006·Cell·Elizabeth J Tran, Susan R Wente
Dec 19, 2006·Proceedings of the National Academy of Sciences of the United States of America·Richard W WongElias Coutavas
Feb 27, 2007·Oncogene·P Peschard, M Park
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Mark G ManfrediChristopher F Claiborne
May 17, 2007·Nature Reviews. Molecular Cell Biology·Mónica Bettencourt-Dias, David M Glover
Mar 19, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Oliver GautschiDavid R Gandara
Aug 19, 2008·Journal of Proteome Research·Patricia AlfonsoJ Ignacio Casal
Oct 4, 2008·Proceedings of the National Academy of Sciences of the United States of America·Richard W Wong, Günter Blobel
Dec 20, 2008·Cell Death and Differentiation·G-H HaC-W Lee
Nov 17, 2009·Cell·Erich A Nigg, Jordan W Raff
May 26, 2010·Molecular Cancer·Chieko HashizumeRichard W Wong
Jun 24, 2010·Nature Reviews. Molecular Cell Biology·Caterina Strambio-De-CastilliaMichael P Rout
Sep 8, 2010·The EMBO Journal·Hannah MüllerBodo M H Lange
Dec 25, 2010·Cell Death and Differentiation·M JiangW Hsu
Jan 29, 2011·Cell Cycle·Hiroshi NakanoRichard W Wong
Feb 8, 2011·Cancer Metastasis Reviews·Tatsuyoshi Funasaka, Richard W Wong
Apr 7, 2011·Cell Cycle·Tatsuyoshi FunasakaRichard W Wong
Jun 21, 2011·Cellular Signalling·Guillaume Chatel, Birthe Fahrenkrog
Oct 22, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mark G ManfrediTodd B Sells
Feb 11, 2012·Current Opinion in Cell Biology·Javier Fernandez-Martinez, Michael P Rout
May 23, 2012·EMBO Reports·Sarah J Pfau, Angelika Amon
Oct 24, 2012·Nature Reviews. Molecular Cell Biology·Marcela Raices, Maximiliano A D'Angelo
Nov 22, 2012·Scientific Reports·Tatsuyoshi FunasakaRichard W Wong
Apr 3, 2013·The Journal of Cell Biology·David ReboutierClaude Prigent
Oct 11, 2013·Cell Cycle·Chieko HashizumeRichard W Wong
Dec 18, 2013·The Journal of Cell Biology·Nina SchweizerHelder Maiato
Feb 25, 2014·Advances in Experimental Medicine and Biology·Dan N Simon, Michael P Rout

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Citations

Jul 31, 2019·Cell Cycle·Suqin ShenMeirong Bai
Aug 8, 2019·Cell Division· HartonoRichard W Wong
Dec 29, 2020·Biochemical and Biophysical Research Communications·Koki KatoRichard W Wong
Feb 15, 2020·Virology·Aditi S KesariDouglas J LaCount
Aug 28, 2021·Cells·Richard W Wong

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Methods Mentioned

BETA
flow cytometry
transfection
immunoprecipitations
immunoprecipitation
pulldown
confocal microscopy
electrophoresis
FACS

Software Mentioned

FACS Diva

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