MPS1

Summary

Gene Symbol: MPS1
Description: serine/threonine/tyrosine protein kinase MPS1
Alias: PAC8, RPK1, serine/threonine/tyrosine protein kinase MPS1
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Keck J, Jones M, Wong C, Binkley J, Chen D, Jaspersen S, et al. A cell cycle phosphoproteome of the yeast centrosome. Science. 2011;332:1557-61 pubmed publisher
    ..Our work establishes the extent and complexity of this prominent posttranslational modification in centrosome biology and provides specific examples of phosphorylation control in centrosome function. ..
  2. Lauzé E, Stoelcker B, Luca F, Weiss E, Schutz A, Winey M. Yeast spindle pole body duplication gene MPS1 encodes an essential dual specificity protein kinase. EMBO J. 1995;14:1655-63 pubmed
    The MPS1 gene has been previously identified by a mutant allele that shows defects in spindle pole body (SPB) duplication and cell cycle control...
  3. Kemmler S, Stach M, Knapp M, Ortiz J, Pfannstiel J, Ruppert T, et al. Mimicking Ndc80 phosphorylation triggers spindle assembly checkpoint signalling. EMBO J. 2009;28:1099-110 pubmed publisher
    The protein kinase Mps1 is, among others, essential for the spindle assembly checkpoint (SAC)...
  4. Holinger E, Old W, Giddings T, Wong C, Yates J, Winey M. Budding yeast centrosome duplication requires stabilization of Spc29 via Mps1-mediated phosphorylation. J Biol Chem. 2009;284:12949-55 pubmed publisher
    ..of Thr(240) was found to promote the stability of the protein in vivo and is catalyzed in vitro by the Mps1 kinase...
  5. Maure J, Kitamura E, Tanaka T. Mps1 kinase promotes sister-kinetochore bi-orientation by a tension-dependent mechanism. Curr Biol. 2007;17:2175-82 pubmed
    ..b>Mps1 is another evolutionarily conserved protein kinase, required for spindle-assembly checkpoint and, in some organisms,..
  6. Shimogawa M, Graczyk B, Gardner M, Francis S, White E, Ess M, et al. Mps1 phosphorylation of Dam1 couples kinetochores to microtubule plus ends at metaphase. Curr Biol. 2006;16:1489-501 pubmed
    ..We show that S221 is one of six Dam1 serines (S13, S49, S217, S218, S221, and S232) phosphorylated by Mps1 in vitro...
  7. Dorer R, Zhong S, Tallarico J, Wong W, Mitchison T, Murray A. A small-molecule inhibitor of Mps1 blocks the spindle-checkpoint response to a lack of tension on mitotic chromosomes. Curr Biol. 2005;15:1070-6 pubmed
    ..gene-deletion strains and traditional genetic and biochemical analysis to show that the target of cincreasin is Mps1, a protein kinase required for checkpoint function [8]...
  8. Jones M, Huneycutt B, Pearson C, Zhang C, Morgan G, Shokat K, et al. Chemical genetics reveals a role for Mps1 kinase in kinetochore attachment during mitosis. Curr Biol. 2005;15:160-5 pubmed
    ..In the budding yeast, Saccharomyces cerevisiae, the highly conserved protein kinase Mps1 has well-characterized roles in spindle pole body (SPB, yeast centrosome equivalent) duplication and the mitotic ..
  9. Rudner A, Hardwick K, Murray A. Cdc28 activates exit from mitosis in budding yeast. J Cell Biol. 2000;149:1361-76 pubmed
    ..The defects of CDC28-VF suggest that Cdc28 activity is required to induce the metaphase to anaphase transition and initiate the transition from anaphase to G1 in budding yeast...

More Information

Publications57

  1. Rudner A, Murray A. Phosphorylation by Cdc28 activates the Cdc20-dependent activity of the anaphase-promoting complex. J Cell Biol. 2000;149:1377-90 pubmed
    ..We show that, like cdc28 mutants, cdc5 mutants affect APC phosphorylation in vivo. However, although Cdc5 can phosphorylate Cdc16 and Cdc27 in vitro, this in vitro phosphorylation does not occur on in vivo sites of phosphorylation. ..
  2. Castillo A, Meehl J, Morgan G, Schutz Geschwender A, Winey M. The yeast protein kinase Mps1p is required for assembly of the integral spindle pole body component Spc42p. J Cell Biol. 2002;156:453-65 pubmed
    Saccharomyces cerevisiae MPS1 encodes an essential protein kinase that has roles in spindle pole body (SPB) duplication and the spindle checkpoint...
  3. Palframan W, Meehl J, Jaspersen S, Winey M, Murray A. Anaphase inactivation of the spindle checkpoint. Science. 2006;313:680-4 pubmed
    ..We demonstrate that, in budding yeast, mutual inhibition between the anaphase-promoting complex (APC) and Mps1, an essential component of the checkpoint, leads to sustained inactivation of the spindle checkpoint...
  4. Jaspersen S, Huneycutt B, Giddings T, Resing K, Ahn N, Winey M. Cdc28/Cdk1 regulates spindle pole body duplication through phosphorylation of Spc42 and Mps1. Dev Cell. 2004;7:263-74 pubmed
    ..The Mps1 kinase, previously shown to regulate Spc42 phosphorylation and assembly, is also a Cdc28 substrate, and Cdc28 ..
  5. Jaspersen S, Giddings T, Winey M. Mps3p is a novel component of the yeast spindle pole body that interacts with the yeast centrin homologue Cdc31p. J Cell Biol. 2002;159:945-56 pubmed
  6. Weiss E, Winey M. The Saccharomyces cerevisiae spindle pole body duplication gene MPS1 is part of a mitotic checkpoint. J Cell Biol. 1996;132:111-23 pubmed
    ..Here we show that the Saccharomyces cerevisiae MPS1 gene product, an essential protein kinase required for spindle pole body (SPB) duplication (Winey et al...
  7. Jones M, Bachant J, Castillo A, Giddings T, Winey M. Yeast Dam1p is required to maintain spindle integrity during mitosis and interacts with the Mps1p kinase. Mol Biol Cell. 1999;10:2377-91 pubmed
    ..We have identified a mutant allele of the DAM1 gene in a screen for mutations that are lethal in combination with the mps1-1 mutation...
  8. Friedman D, Kern J, Huneycutt B, Vinh D, Crawford D, Steiner E, et al. Yeast Mps1p phosphorylates the spindle pole component Spc110p in the N-terminal domain. J Biol Chem. 2001;276:17958-67 pubmed
    ..Sites of Mps1p phosphorylation and Ser(36) are located within the N-terminal globular domain of Spc110p, which resides at the inner plaque of the SPB and binds the Tub4p complex. ..
  9. Biggins S, Murray A. The budding yeast protein kinase Ipl1/Aurora allows the absence of tension to activate the spindle checkpoint. Genes Dev. 2001;15:3118-29 pubmed
    ..Ipl1p is required to maintain the spindle checkpoint that is induced by overexpression of the protein kinase Mps1. Inactivating Ipl1p allows cells overexpressing Mps1p to escape from mitosis and segregate their chromosomes ..
  10. Warren C, Brady D, Johnston R, Hanna J, Hardwick K, Spencer F. Distinct chromosome segregation roles for spindle checkpoint proteins. Mol Biol Cell. 2002;13:3029-41 pubmed
    ..Analysis of this activity indicates that the Bub3p-binding domain of Bub1p contributes to this phenotype through disruption of checkpoint activity as well as through introduction of kinetochore or spindle damage. ..
  11. Snead J, Sullivan M, Lowery D, Cohen M, Zhang C, Randle D, et al. A coupled chemical-genetic and bioinformatic approach to Polo-like kinase pathway exploration. Chem Biol. 2007;14:1261-72 pubmed
    ..Finally, an examination of Cdc5 binding by SPB-localized proteins expanded our knowledge of Cdc5 function at the SPB. ..
  12. Geiser J, Schott E, Kingsbury T, Cole N, Totis L, Bhattacharyya G, et al. Saccharomyces cerevisiae genes required in the absence of the CIN8-encoded spindle motor act in functionally diverse mitotic pathways. Mol Biol Cell. 1997;8:1035-50 pubmed
    ..These findings illustrate the complex cellular interactions exhibited by Cin8p, a member of a conserved spindle motor family. ..
  13. Schutz A, Giddings T, Steiner E, Winey M. The yeast CDC37 gene interacts with MPS1 and is required for proper execution of spindle pole body duplication. J Cell Biol. 1997;136:969-82 pubmed
    The MPS1 gene from Saccharomyces cerevisiae encodes an essential protein kinase required for spindle pole body (SPB) duplication and for the mitotic spindle assembly checkpoint...
  14. Hardwick K, Weiss E, Luca F, Winey M, Murray A. Activation of the budding yeast spindle assembly checkpoint without mitotic spindle disruption. Science. 1996;273:953-6 pubmed
    ..The protein kinase Mps1 phosphorylates the yeast protein Mad1p when this checkpoint is activated, and the overexpression of Mps1p induces ..
  15. Winey M, Goetsch L, Baum P, Byers B. MPS1 and MPS2: novel yeast genes defining distinct steps of spindle pole body duplication. J Cell Biol. 1991;114:745-54 pubmed
    ..Newly isolated mutations described here (mps1 and mps2, for monopolar spindle) similarly cause monopolar mitosis but their underlying effects on SPB duplication ..
  16. London N, Biggins S. Mad1 kinetochore recruitment by Mps1-mediated phosphorylation of Bub1 signals the spindle checkpoint. Genes Dev. 2014;28:140-52 pubmed publisher
    ..yeast is mediated by phosphorylation of a region within the Bub1 checkpoint protein by the conserved protein kinase Mps1. Tethering this region of Bub1 to kinetochores bypasses the checkpoint requirement for Mps1-mediated kinetochore ..
  17. Araki Y, Lau C, Maekawa H, Jaspersen S, Giddings T, Schiebel E, et al. The Saccharomyces cerevisiae spindle pole body (SPB) component Nbp1p is required for SPB membrane insertion and interacts with the integral membrane proteins Ndc1p and Mps2p. Mol Biol Cell. 2006;17:1959-70 pubmed
    ..These results demonstrate that Nbp1p is a SPB component that acts in SPB duplication at the point of SPB insertion into the nuclear envelope. ..
  18. Liu C, van Dyk D, Choe V, Yan J, Majumder S, Costanzo M, et al. Ubiquitin ligase Ufd2 is required for efficient degradation of Mps1 kinase. J Biol Chem. 2011;286:43660-7 pubmed publisher
    ..Here, we show that ubiquitylation and degradation of the cell cycle kinase Mps1, a known target of the anaphase-promoting complex E3, require Ufd2 enzyme...
  19. Araki Y, Gombos L, Migueleti S, Sivashanmugam L, Antony C, Schiebel E. N-terminal regions of Mps1 kinase determine functional bifurcation. J Cell Biol. 2010;189:41-56 pubmed publisher
    b>Mps1 is a conserved kinase that in budding yeast functions in duplication of the spindle pole body (SPB), spindle checkpoint activation, and kinetochore biorientation...
  20. Ostapenko D, Burton J, Solomon M. Identification of anaphase promoting complex substrates in S. cerevisiae. PLoS ONE. 2012;7:e45895 pubmed publisher
    ..the transcription factors Tos4 and Pdr3; the mRNA processing factor Fir1; the spindle checkpoint protein kinase Mps1; and a protein of unknown function, Ybr138C...
  21. Makhnevych T, Wong P, Pogoutse O, Vizeacoumar F, Greenblatt J, Emili A, et al. Hsp110 is required for spindle length control. J Cell Biol. 2012;198:623-36 pubmed publisher
    ..These data suggest a model whereby the Hsp70-Hsp110 chaperone complex antagonizes Cin8 plus-end motility and prevents premature spindle elongation in S phase. ..
  22. Luca F, Winey M. MOB1, an essential yeast gene required for completion of mitosis and maintenance of ploidy. Mol Biol Cell. 1998;9:29-46 pubmed
    ..The mechanism for the increase in ploidy may occur through MPS1 function...
  23. Ólafsson G, Thorpe P. Synthetic Physical Interactions Map Kinetochore-Checkpoint Activation Regions. G3 (Bethesda). 2016;6:2531-42 pubmed publisher
    ..This recruitment is coordinated by the SAC kinase Mps1, which phosphorylates residues at the kinetochore to facilitate binding of Bub1, Bub3, Mad1, and Mad2...
  24. Abruzzi K, Magendantz M, Solomon F. An alpha-tubulin mutant demonstrates distinguishable functions among the spindle assembly checkpoint genes in Saccharomyces cerevisiae. Genetics. 2002;161:983-94 pubmed
    ..sensitivity of tub1-729 is suppressed by extra copies of a subset of the mitotic checkpoint genes BUB1, BUB3, and MPS1, but not MAD1, MAD2, and MAD3...
  25. Alimova I, Ng J, Harris P, Birks D, Donson A, Taylor M, et al. MPS1 kinase as a potential therapeutic target in medulloblastoma. Oncol Rep. 2016;36:2633-2640 pubmed publisher
    ..Gene expression profiling has revealed that monopolar spindle 1 (MPS1) (TTK1) is highly expressed in medulloblastoma patient samples compared to that noted in normal cerebellum...
  26. Faisal A, Mak G, Gurden M, Xavier C, Anderhub S, Innocenti P, et al. Characterisation of CCT271850, a selective, oral and potent MPS1 inhibitor, used to directly measure in vivo MPS1 inhibition vs therapeutic efficacy. Br J Cancer. 2017;116:1166-1176 pubmed publisher
    ..b>MPS1 kinase activity is essential for the activation of the spindle assembly checkpoint and has been shown to be ..
  27. Komarnitsky S, Chiang Y, Luca F, Chen J, Toyn J, Winey M, et al. DBF2 protein kinase binds to and acts through the cell cycle-regulated MOB1 protein. Mol Cell Biol. 1998;18:2100-7 pubmed
    ..We discuss models concerning the role of DBF2 and MOB1 in controlling the telophase/G1 transition. ..
  28. Schott E, Hoyt M. Dominant alleles of Saccharomyces cerevisiae CDC20 reveal its role in promoting anaphase. Genetics. 1998;148:599-610 pubmed
    ..defect, causing bypass of the preanaphase arrest produced by either microtubule-depolymerizing compounds or MPS1 overexpression...
  29. Lai L, Morabito L, Holloway S. A novel yeast mutant that is defective in regulation of the Anaphase-Promoting Complex by the spindle damage checkpoint. Mol Genet Genomics. 2003;270:156-64 pubmed
    ..Our results suggest that the cdc16-183 mutant may have a novel APC/C defect(s) that mimics or activates the spindle checkpoint pathway. ..
  30. Thapa K, Oldani A, Pagliuca C, De Wulf P, Hazbun T. The Mps1 kinase modulates the recruitment and activity of Cnn1(CENP-T) at Saccharomyces cerevisiae kinetochores. Genetics. 2015;200:79-90 pubmed publisher
    ..Cnn1 localization was proposed to depend on Mps1 kinase activity at Cnn1-S74, based on in vitro experiments demonstrating the Cnn1-Ndc80 complex interaction...
  31. Han X, Wang Y, Aslanian A, Fonslow B, Graczyk B, Davis T, et al. In-line separation by capillary electrophoresis prior to analysis by top-down mass spectrometry enables sensitive characterization of protein complexes. J Proteome Res. 2014;13:6078-86 pubmed publisher
    ..5 ng (12 amol). N-terminal processing forms of individual subunits of the Dam1 complex were observed as well as their phosphorylation stoichiometry upon Mps1p kinase treatment. ..
  32. Lin T, Neuner A, Schlosser Y, Scharf A, Weber L, Schiebel E. Cell-cycle dependent phosphorylation of yeast pericentrin regulates ?-TuSC-mediated microtubule nucleation. elife. 2014;3:e02208 pubmed publisher
    ..Here we show that Spc110 phosphorylated by Mps1 and Cdk1 activates ?-TuSC oligomerization and MT nucleation in a cell cycle dependent manner...
  33. Malvezzi F, Litos G, Schleiffer A, Heuck A, Mechtler K, Clausen T, et al. A structural basis for kinetochore recruitment of the Ndc80 complex via two distinct centromere receptors. EMBO J. 2013;32:409-23 pubmed publisher
    ..Together, our data provide structural insights into the modular binding mechanism of the Ndc80 complex to its centromere recruiters...
  34. Valerio Santiago M, de Los Santos Velázquez A, Monje Casas F. Inhibition of the mitotic exit network in response to damaged telomeres. PLoS Genet. 2013;9:e1003859 pubmed publisher
  35. Lim G, Huh W. Rad52 phosphorylation by Ipl1 and Mps1 contributes to Mps1 kinetochore localization and spindle assembly checkpoint regulation. Proc Natl Acad Sci U S A. 2017;114:E9261-E9270 pubmed publisher
    ..unrelated to homologous recombination in Saccharomyces cerevisiae; it plays a role in the recruitment of Mps1 to the kinetochores and the maintenance of spindle assembly checkpoint (SAC) activity...
  36. Bock L, Pagliuca C, Kobayashi N, Grove R, Oku Y, Shrestha K, et al. Cnn1 inhibits the interactions between the KMN complexes of the yeast kinetochore. Nat Cell Biol. 2012;14:614-24 pubmed publisher
    ..KMN-spindle attachment is regulated by the Aurora B(Ipl1) and MPS1(Mps1) kinases. It is unclear whether other mechanisms exist that support KMN activity during the cell cycle...
  37. London N, Ceto S, Ranish J, Biggins S. Phosphoregulation of Spc105 by Mps1 and PP1 regulates Bub1 localization to kinetochores. Curr Biol. 2012;22:900-6 pubmed publisher
    ..Checkpoint activity is correlated with the recruitment of checkpoint proteins to the kinetochore. Mps1 is a conserved protein kinase that regulates segregation and the spindle checkpoint, but few of the targets that ..
  38. Storchova Z, Becker J, Talarek N, Kögelsberger S, Pellman D. Bub1, Sgo1, and Mps1 mediate a distinct pathway for chromosome biorientation in budding yeast. Mol Biol Cell. 2011;22:1473-85 pubmed publisher
    ..Instead we identify Sgo1 as a possible partner of Mps1, a mitotic kinase suggested to have an Aurora B-independent function in establishment of biorientation...
  39. Hwang H, Song K. IBD2 encodes a novel component of the Bub2p-dependent spindle checkpoint in the budding yeast Saccharomyces cerevisiae. Genetics. 2002;161:595-609 pubmed
    ..as well as in bub2Delta, suggesting that IBD2 encodes a novel component of the spindle checkpoint downstream of MPS1. Overexpression of Ibd2p induced mitotic arrest with increased levels of Clb2p in wild type and mad2Delta, but not ..
  40. Fonslow B, Kang S, Gestaut D, Graczyk B, Davis T, Sabatini D, et al. Native capillary isoelectric focusing for the separation of protein complex isoforms and subcomplexes. Anal Chem. 2010;82:6643-51 pubmed publisher
    ..of two different phosphorylation states of the Dam1 complex, generated from an in vitro kinase assay with Mps1 kinase, was straightforward due to the large pI shift upon multiple phosphorylation events...
  41. Bandhakavi S, McCann R, Hanna D, Glover C. A positive feedback loop between protein kinase CKII and Cdc37 promotes the activity of multiple protein kinases. J Biol Chem. 2003;278:2829-36 pubmed
    ..Collectively, these data define a positive feedback loop between CKII and Cdc37. Additional genetic assays demonstrate that this CKII/Cdc37 interaction positively regulates the activity of multiple protein kinases in addition to CKII. ..
  42. Mort Bontemps Soret M, Facca C, Faye G. Physical interaction of Cdc28 with Cdc37 in Saccharomyces cerevisiae. Mol Genet Genomics. 2002;267:447-58 pubmed
    ..This was not the case for the full-length Cdc28 protein. We present models to explain these results. ..
  43. Cheeseman I, Enquist Newman M, MULLER REICHERT T, Drubin D, Barnes G. Mitotic spindle integrity and kinetochore function linked by the Duo1p/Dam1p complex. J Cell Biol. 2001;152:197-212 pubmed
    ..In addition, Duo1p and Dam1p localize to kinetochores in chromosome spreads, suggesting that this complex may serve as a link between the kinetochore and the mitotic spindle. ..
  44. Meyer R, Kim S, Obeso D, Straight P, Winey M, Dawson D. Mps1 and Ipl1/Aurora B act sequentially to correctly orient chromosomes on the meiotic spindle of budding yeast. Science. 2013;339:1071-4 pubmed publisher
    The conserved kinases Mps1 and Ipl1/Aurora B are critical for enabling chromosomes to attach to microtubules so that partner chromosomes will be segregated correctly from each other, but the precise roles of these kinases have been ..
  45. Pinsky B, Nelson C, Biggins S. Protein phosphatase 1 regulates exit from the spindle checkpoint in budding yeast. Curr Biol. 2009;19:1182-7 pubmed publisher
    ..We therefore propose that PP1 activity silences the checkpoint by reversing key phosphorylation events. ..
  46. Chiroli E, Rancati G, Catusi I, Lucchini G, Piatti S. Cdc14 inhibition by the spindle assembly checkpoint prevents unscheduled centrosome separation in budding yeast. Mol Biol Cell. 2009;20:2626-37 pubmed publisher
    ..We propose that, besides inhibiting sister chromatid separation, the SAC preserves the accurate transmission of chromosomes also by preventing SPBs to migrate far apart until the conditions to assemble a bipolar spindle are satisfied. ..
  47. Bekier M, Mazur T, Rashid M, Taylor W. Borealin dimerization mediates optimal CPC checkpoint function by enhancing localization to centromeres and kinetochores. Nat Commun. 2015;6:6775 pubmed publisher
    ..Finally, Haspin kinase plays a key role in maintaining the slowly exchanging centromere Borealin pool, while Aurora B and Mps1 play minimal roles in maintaining CPC localization once cells are in mitosis.
  48. Smith J, Rose M. Kel1p Mediates Yeast Cell Fusion Through a Fus2p- and Cdc42p-Dependent Mechanism. Genetics. 2016;202:1421-35 pubmed publisher