Dissecting the role of MPS1 in chromosome biorientation and the spindle checkpoint through the small molecule inhibitor reversine.

The Journal of Cell Biology
Stefano SantaguidaAndrea Musacchio

Abstract

The catalytic activity of the MPS1 kinase is crucial for the spindle assembly checkpoint and for chromosome biorientation on the mitotic spindle. We report that the small molecule reversine is a potent mitotic inhibitor of MPS1. Reversine inhibits the spindle assembly checkpoint in a dose-dependent manner. Its addition to mitotic HeLa cells causes the ejection of Mad1 and the ROD-ZWILCH-ZW10 complex, both of which are important for the spindle checkpoint, from unattached kinetochores. By using reversine, we also demonstrate that MPS1 is required for the correction of improper chromosome-microtubule attachments. We provide evidence that MPS1 acts downstream from the AURORA B kinase, another crucial component of the error correction pathway. Our experiments describe a very useful tool to interfere with MPS1 activity in human cells. They also shed light on the relationship between the error correction pathway and the spindle checkpoint and suggest that these processes are coregulated and are likely to share at least a subset of their catalytic machinery.

References

Apr 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·A HemerlyP Ferreira
Jan 1, 1991·Cold Spring Harbor Symposia on Quantitative Biology·J R McIntosh
Nov 3, 1989·Science·L H Hartwell, T A Weinert
Feb 16, 1995·Nature·X Li, R B Nicklas
Mar 15, 2003·Science·Aaron F StraightTimothy J Mitchison
Apr 30, 2003·The Journal of Cell Biology·Claire DitchfieldStephen S Taylor
Oct 29, 2003·Molecular Cell·Richard BaylissElena Conti
Jan 15, 2004·Journal of the American Chemical Society·Shuibing ChenSheng Ding
Feb 10, 2004·Nature Cell Biology·Michael A LampsonTarun M Kapoor
Feb 13, 2004·Developmental Cell·Paul D AndrewsJason R Swedlow
Jun 9, 2004·Current Biology : CB·Bonnie J HowellE D Salmon
Jul 9, 2004·Developmental Cell·Patrick MeraldiPeter K Sorger
Jul 23, 2004·Molecular Biology of the Cell·Suzanne VigneronThierry Lorca
Jan 26, 2005·Current Biology : CB·Michele H JonesMark Winey
Feb 8, 2005·Current Biology : CB·Anna De AntoniAndrea Musacchio
Aug 9, 2005·Trends in Cell Biology·Benjamin A Pinsky, Sue Biggins
Aug 23, 2005·EMBO Reports·Marc SchmidtRené H Medema
Dec 13, 2005·Molecular & Cellular Proteomics : MCP·Eiji KinoshitaTohru Koike
Aug 8, 2006·Current Biology : CB·Michelle M ShimogawaTrisha N Davis
Sep 5, 2006·Current Biology : CB·Anne Lide KnowltonP Todd Stukenberg
Oct 19, 2006·Current Opinion in Cell Biology·Beth A A Weaver, Don W Cleveland
Feb 13, 2007·Current Biology : CB·Péter LénártJan-Michael Peters
Apr 12, 2007·Nature Reviews. Molecular Cell Biology·Andrea Musacchio, Edward D Salmon
Jun 15, 2007·Proceedings of the National Academy of Sciences of the United States of America·Shuibing ChenPeter G Schultz
Aug 31, 2007·The Journal of Biological Chemistry·Christopher P MattisonMark Winey
Sep 13, 2007·Nature Reviews. Molecular Cell Biology·Sandrine RuchaudWilliam C Earnshaw
Dec 7, 2007·Current Biology : CB·Jean-François MaureTomoyuki U Tanaka
Dec 11, 2007·Current Biology : CB·Jakub K Famulski, Gordon K Chan
Dec 18, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jungseog KangHongtao Yu
Mar 18, 2008·Molecular Cell·Julien EspeutAriane Abrieu
Apr 23, 2008·The Journal of Cell Biology·Michael J EmanueleP Todd Stukenberg

❮ Previous
Next ❯

Citations

Feb 1, 2012·Chromosoma·Bungo Akiyoshi, Sue Biggins
Jun 19, 2013·Chromosoma·Anna-Leena Salmela, Marko J Kallio
Oct 14, 2011·ACS Chemical Biology·Nicholas KwiatkowskiNathanael Gray
May 9, 2012·Nature Cell Biology·Lucy J BockPeter De Wulf
Jun 5, 2012·Nature Cell Biology·Yuya YamagishiYoshinori Watanabe
Oct 8, 2013·Nature Cell Biology·Philippe CollinJonathon Pines
May 19, 2011·Nature Communications·Adrian T SaurinGeert J P L Kops
Apr 30, 2011·Nature Reviews. Molecular Cell Biology·Ilio VitaleGuido Kroemer
Dec 22, 2012·Nature Reviews. Molecular Cell Biology·Emily A Foley, Tarun M Kapoor
Mar 13, 2012·Nature Structural & Molecular Biology·Makoto T HayashiJan Karlseder
Feb 23, 2011·Oncogene·A Janssen, R H Medema
Dec 21, 2011·Proceedings of the National Academy of Sciences of the United States of America·Daisuke ItoTomohiro Matsumoto
May 4, 2012·Proceedings of the National Academy of Sciences of the United States of America·Agnieszka KolanoMarie-Hélène Verlhac
Oct 5, 2010·The Journal of Biological Chemistry·Tingting SunXuedong Liu
Dec 18, 2013·The Journal of Cell Biology·Nina SchweizerHelder Maiato
Mar 11, 2011·Molecular Biology of the Cell·Zuzana StorchováDavid Pellman
Jul 22, 2011·Molecular Biology of the Cell·James M KasuboskiKevin T Vaughan
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
Mar 20, 2012·Genes & Development·Daniel R MatsonDaniel J Burke
Apr 16, 2011·Cell Division·Amanda N Pike, Harold A Fisk
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 13, 2014·The Journal of Cell Biology·Budhaditya BanerjeeP Todd Stukenberg
Apr 10, 2012·Annual Review of Biochemistry·Xuedong Liu, Mark Winey
May 28, 2014·The Journal of Cell Biology·Daniel R Matson, P Todd Stukenberg
May 7, 2014·The Journal of Cell Biology·Eleni Petsalaki, George Zachos
Mar 23, 2012·EMBO Molecular Medicine·Mohamed JemaàGuido Kroemer
Nov 18, 2014·Nature Cell Biology·Wilco NijenhuisAdrian T Saurin
Jul 4, 2012·Cellular and Molecular Life Sciences : CMLS·Kozo Tanaka
Oct 17, 2012·The Journal of Cell Biology·Anna De AntoniStefano Santaguida
Sep 8, 2010·The Journal of Cell Biology·Arsen PetrovicAndrea Musacchio

❮ Previous
Next ❯

Methods Mentioned

BETA
size exclusion chromatography

Software Mentioned

AURORA
ScanR
Leica
Prism
ImageJ
GraphPad
SoftWoRx
Photoshop CS3
LCS 3D

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.