Sustained Mps1 activity is required in mitosis to recruit O-Mad2 to the Mad1-C-Mad2 core complex.

The Journal of Cell Biology
Laura HewittStephen S Taylor

Abstract

Mps1 is an essential component of the spindle assembly checkpoint. In this study, we describe a novel Mps1 inhibitor, AZ3146, and use it to probe the role of Mps1's catalytic activity during mitosis. When Mps1 is inhibited before mitotic entry, subsequent recruitment of Mad1 and Mad2 to kinetochores is abolished. However, if Mps1 is inhibited after mitotic entry, the Mad1-C-Mad2 core complex remains kinetochore bound, but O-Mad2 is not recruited to the core. Although inhibiting Mps1 also interferes with chromosome alignment, we see no obvious effect on aurora B activity. In contrast, kinetochore recruitment of centromere protein E (CENP-E), a kinesin-related motor protein, is severely impaired. Strikingly, inhibition of Mps1 significantly increases its own abundance at kinetochores. Furthermore, we show that Mps1 can dimerize and transphosphorylate in cells. We propose a model whereby Mps1 transphosphorylation results in its release from kinetochores, thus facilitating recruitment of O-Mad2 and CENP-E and thereby simultaneously promoting checkpoint signaling and chromosome congression.

References

May 15, 2002·Molecular Biology of the Cell·Eunah Chung, Rey-Huei Chen
Apr 11, 2003·Molecular Biology of the Cell·Song-Tao LiuTim J Yen
Apr 30, 2003·The Journal of Cell Biology·Claire DitchfieldStephen S Taylor
Mar 17, 2004·Journal of Cell Science·Victoria L JohnsonStephen S Taylor
Jun 9, 2004·Current Biology : CB·Bonnie J HowellE D Salmon
Jul 28, 2005·Journal of Cell Science·Christopher J MorrowStephen S Taylor
Dec 13, 2005·Molecular & Cellular Proteomics : MCP·Eiji KinoshitaTohru Koike
Jan 21, 2006·Science·Tarun M KapoorAlexey Khodjakov
Apr 25, 2006·Current Biology : CB·Martin VinkAndrea Musacchio
Apr 12, 2007·Nature Reviews. Molecular Cell Biology·Andrea Musacchio, Edward D Salmon
Jul 3, 2007·The Journal of Biological Chemistry·Andrew J HollandStephen S Taylor
Dec 7, 2007·Current Biology : CB·Jean-François MaureTomoyuki U Tanaka
Dec 18, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jungseog KangHongtao Yu
May 16, 2008·The Journal of Biological Chemistry·Matthew L H ChuLydia Tabernero
Jun 11, 2008·The Journal of Cell Biology·Anthony TigheStephen Taylor
Apr 13, 2010·Nature Chemical Biology·Nicholas KwiatkowskiNathanael S Gray

❮ Previous
Next ❯

Citations

Feb 1, 2012·Chromosoma·Bungo Akiyoshi, Sue Biggins
Mar 21, 2013·Chromosoma·Hironori Funabiki, David J Wynne
Jun 19, 2013·Chromosoma·Anna-Leena Salmela, Marko J Kallio
Oct 8, 2013·Nature Cell Biology·Philippe CollinJonathon Pines
May 19, 2011·Nature Communications·Adrian T SaurinGeert J P L Kops
Dec 22, 2012·Nature Reviews. Molecular Cell Biology·Emily A Foley, Tarun M Kapoor
Dec 21, 2011·Proceedings of the National Academy of Sciences of the United States of America·Daisuke ItoTomohiro Matsumoto
Dec 18, 2013·The Journal of Cell Biology·Nina SchweizerHelder Maiato
Mar 11, 2011·Molecular Biology of the Cell·Zuzana StorchováDavid Pellman
May 4, 2012·Molecular Biology of the Cell·Friederike AlthoffChristian F Lehner
Aug 14, 2013·Journal of the National Cancer Institute·Bakhos A TannousThomas Würdinger
Nov 16, 2011·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Andrea Musacchio
Nov 16, 2011·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Jonathon Pines, Iain Hagan
Oct 11, 2011·Cancer Discovery·Rachel BroughAlan Ashworth
Apr 16, 2011·Cell Division·Amanda N Pike, Harold A Fisk
Nov 22, 2011·Journal of Cell Science·Frederick G WesthorpeStephen S Taylor
Feb 19, 2013·Journal of Cell Science·Dileep Varma, E D Salmon
Oct 11, 2012·PloS One·Eduardo Alves Gamosa de OliveiraMarco Antônio Lopes Cruz
Mar 4, 2014·Nature Chemical Biology·Pietro CiceriStefan Knapp
Mar 19, 2014·The Journal of Cell Biology·Ibtissem NabtiJohn Carroll
Mar 19, 2014·The Journal of Cell Biology·Edward R BallisterMichael A Lampson
Apr 10, 2012·Annual Review of Biochemistry·Xuedong Liu, Mark Winey
May 7, 2014·The Journal of Cell Biology·Eleni Petsalaki, George Zachos
Mar 23, 2012·EMBO Molecular Medicine·Mohamed JemaàGuido Kroemer
Sep 24, 2014·The Journal of Cell Biology·Antonio EspertUlrike Gruneberg
Nov 18, 2014·Nature Cell Biology·Wilco NijenhuisAdrian T Saurin
Jul 4, 2012·Cellular and Molecular Life Sciences : CMLS·Kozo Tanaka
Jul 14, 2010·The Journal of Cell Biology·Weijie Lan, Don W Cleveland
Oct 26, 2011·The Journal of Cell Biology·Eleni PetsalakiGeorge Zachos
Oct 13, 2010·The Journal of Cell Biology·Nannette JellumaGeert J P L Kops
Apr 10, 2013·The Journal of Cell Biology·Wilco NijenhuisGeert J P L Kops
Feb 3, 2016·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Tatiana V DenisenkoBoris Zhivotovsky
Aug 5, 2015·Proceedings of the National Academy of Sciences of the United States of America·Zhen DouXuebiao Yao
Aug 26, 2015·Proceedings of the National Academy of Sciences of the United States of America·Mayuko HaraXuelian Luo
Mar 29, 2011·Seminars in Cell & Developmental Biology·Soonjoung Kim, Hongtao Yu
Mar 29, 2011·Seminars in Cell & Developmental Biology·Robin M Ricke, Jan M van Deursen

❮ Previous
Next ❯

Methods Mentioned

BETA
immunoprecipitation
chip
PCR

Software Mentioned

AIDA
Raytest
SoftWorx
SelectScreen
QuickTime
PhotoShop
MetaMorph

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.