Research Topics
Genomes and GenesSpecies | Geert J P L KopsSummaryAffiliation: University Medical Center Utrecht Country: The Netherlands Publications
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Publications
Connecting up and clearing out: how kinetochore attachment silences the spindle assembly checkpointGeert J P L Kops
Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
Chromosoma 121:509-25. 2012..Future challenges in this area are highlighted towards the goal of building a comprehensive molecular model of this process...
Dividing the goods: co-ordination of chromosome biorientation and mitotic checkpoint signalling by mitotic kinasesGeert J P L Kops
Department of Physiological Chemistry and Cancer Genomics Centre, UMC Utrecht, Utrecht, The Netherlands
Biochem Soc Trans 37:971-5. 2009..A group of unrelated kinases controls various aspects of both processes. The present short review outlines our current understanding of the roles of these kinases in maintaining chromosomal stability...
The kinetochore and spindle checkpoint in mammalsGeert J P L Kops
Department of Physiological Chemistry, UMC Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands
Front Biosci 13:3606-20. 2008..This review focuses on molecular aspects of mitotic checkpoint signaling in mammals, including sensing improper attachments and transducing this information to the cell-cycle machinery...
Finding the middle ground: how kinetochores power chromosome congressionGeert J P L Kops
Department of Physiological Chemistry and Cancer Genomics Centre, University Medical Center Utrecht, Stratenum 3 217, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands
Cell Mol Life Sci 67:2145-61. 2010..Here we review the current knowledge and concepts on the processes that underlie chromosome congression, including initial attachment to spindle microtubules, biorientation, and movements, from the perspective of the kinetochore...
APC16 is a conserved subunit of the anaphase-promoting complex/cyclosomeGeert J P L Kops
Department of Physiological Chemistry and Cancer Genomics Centre, UMC Utrecht, Utrecht, The Netherlands
J Cell Sci 123:1623-33. 2010..rerio gene zgc:110659 are functional equivalents of human APC16. Our findings show that APC/C is composed of previously undescribed subunits, and raise the question of why metazoan APC/C is molecularly different from unicellular APC/C...
Molecular causes for BUBR1 dysfunction in the human cancer predisposition syndrome mosaic variegated aneuploidySaskia J E Suijkerbuijk
Department of Physiological Chemistry and Cancer Genomics Centre, University Medical Center Utrecht, Utrecht, The Netherlands
Cancer Res 70:4891-900. 2010..Our findings provide a molecular explanation for chromosomal instability in patients with biallelic genetic mutations in BUBR1...
Chromosomal instability by inefficient Mps1 auto-activation due to a weakened mitotic checkpoint and lagging chromosomesNannette Jelluma
Department of Physiological Chemistry and Cancer Genomics Centre, UMC Utrecht, Utrecht, The Netherlands
PLoS ONE 3:e2415. 2008..Two of the causes of CIN are weakened mitotic checkpoint signaling and persistent merotelic attachments that result in lagging chromosomes during anaphase...
Release of Mps1 from kinetochores is crucial for timely anaphase onsetNannette Jelluma
Department of Physiological Chemistry and Cancer Genomics Centre, UMC Utrecht, 3584 CG, Utrecht, Netherlands
J Cell Biol 191:281-90. 2010..We propose that release of Mps1 from kinetochores is essential for mitotic checkpoint silencing and a fast metaphase-to-anaphase transition...
Mps1 phosphorylates Borealin to control Aurora B activity and chromosome alignmentNannette Jelluma
Department of Medical Oncology, Laboratory of Experimental Oncology, UMC Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands
Cell 132:233-46. 2008..Mps1 thus coordinates attachment error correction and checkpoint signaling, two crucial responses to unproductive chromosome attachments...
Chromosome segregation errors as a cause of DNA damage and structural chromosome aberrationsAniek Janssen
Department of Medical Oncology and Cancer Genomics Center, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, Netherlands
Science 333:1895-8. 2011..Our data show that segregation errors can cause translocations and provide insights into the role of whole-chromosome instability in tumorigenesis...
Elevating the frequency of chromosome mis-segregation as a strategy to kill tumor cellsAniek Janssen
Department of Medical Oncology, Cancer Genomics Center, UMC Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands
Proc Natl Acad Sci U S A 106:19108-13. 2009..Thus, targeting the mitotic checkpoint and chromosome alignment simultaneously may selectively kill tumor cells by enhancing chromosome mis-segregations...
Aurora B potentiates Mps1 activation to ensure rapid checkpoint establishment at the onset of mitosisAdrian T Saurin
Molecular Cancer Research and Cancer Genomics Centre, University Medical Center Utrecht, Utrecht 3584 CG, The Netherlands
Nat Commun 2:316. 2011..These data demonstrate a direct role for Aurora B in initiating the mitotic checkpoint rapidly at the onset of mitosis...
Integration of kinase and phosphatase activities by BUBR1 ensures formation of stable kinetochore-microtubule attachmentsSaskia J E Suijkerbuijk
Molecular Cancer Research and Cancer Genomics Centre, UMC Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
Dev Cell 23:745-55. 2012..We propose that PLK1 and BUBR1 cooperate to stabilize kinetochore-microtubule interactions by regulating PP2A-B56α-mediated dephosphorylation of Aurora B substrates at the kinetochore-microtubule interface...
Preventing aneuploidy: the contribution of mitotic checkpoint proteinsSaskia J E Suijkerbuijk
Department of Physiological Chemistry, UMC Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
Biochim Biophys Acta 1786:24-31. 2008..We propose that both checkpoint and non-checkpoint functions of these proteins contribute to the wide array of oncogenic phenotypes seen upon their misregulation...
Chemical genetic inhibition of Mps1 in stable human cell lines reveals novel aspects of Mps1 function in mitosisTale Sliedrecht
Department of Physiological Chemistry, Cancer Genomics Centre, University Medical Center Utrecht, Utrecht, The Netherlands
PLoS ONE 5:e10251. 2010..Proper functioning of the attachment and checkpoint processes is thus important to prevent chromosomal instability. Both processes rely on the mitotic kinase Mps1...
Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stressGeert J P L Kops
Department of Physiological Chemistry, University Medical Center Utrecht and Center for Biomedical Genetics, 3584 CG Utrecht, The Netherlands
Nature 419:316-21. 2002..The model of Forkhead involvement in regulating longevity stems from genetic analysis in Caenorhabditis elegans, and we conclude that this model also extends to mammalian systems...
Mps1 promotes rapid centromere accumulation of Aurora BMaike S van der Waal
Department of Medical Oncology, University Medical Center Utrecht, Universiteitsweg 100, STR 2 129, 3584 CG Utrecht, The Netherlands
EMBO Rep 13:847-54. 2012....
A phospho/methyl switch at histone H3 regulates TFIID association with mitotic chromosomesRadhika A Varier
Department of Physiological Chemistry and Netherlands Proteomics Center, University Medical Centre Utrecht, Utrecht, The Netherlands
EMBO J 29:3967-78. 2010..Based on our observations, we propose that a histone H3 phospho-methyl switch regulates TFIID-mediated transcription during mitotic progression of the cell cycle...
The vertebrate mitotic checkpoint protein BUBR1 is an unusual pseudokinaseSaskia J E Suijkerbuijk
Molecular Cancer Research and Cancer Genomics Centre, Department of Medical Oncology, UMC Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
Dev Cell 22:1321-9. 2012..We propose that parallel evolution of BUBR1 orthologs rendered its kinase function dispensable in vertebrates, producing an unusual, triad-containing pseudokinase...
Evolution and function of the mitotic checkpointMathijs Vleugel
Department of Medical Oncology, Department of Molecular Cancer Research and Cancer Genomics Centre, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands
Dev Cell 23:239-50. 2012....
Control of cell cycle exit and entry by protein kinase B-regulated forkhead transcription factorsGeert J P L Kops
Department of Physiological Chemistry, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands
Mol Cell Biol 22:2025-36. 2002..We therefore propose that Forkhead inactivation by PKB signaling in quiescent cells is a crucial step in cell cycle reentry and contributes to the processes of transformation and regeneration...
On the road to cancer: aneuploidy and the mitotic checkpointGeert J P L Kops
Laboratory of Experimental Oncology, Department of Medical Oncology, University Medical Center, Utrecht, 3584 CG, The Netherlands
Nat Rev Cancer 5:773-85. 2005..Defects in the mitotic checkpoint generate aneuploidy and might facilitate tumorigenesis, but more severe disabling of checkpoint signalling is a possible anticancer strategy...
Centromere-associated protein-E is essential for the mammalian mitotic checkpoint to prevent aneuploidy due to single chromosome lossBeth A A Weaver
Ludwig Institute for Cancer Research, 3080 CMM East, 9500 Gilman Drive, La Jolla, CA 92093 0670, USA
J Cell Biol 162:551-63. 2003..Thus, CENP-E is required for enhancing recruitment of its binding partner BubR1 to each unattached kinetochore and for stimulating BubR1 kinase activity, implicating it as an essential amplifier of a basal mitotic checkpoint signal...
ZW10 links mitotic checkpoint signaling to the structural kinetochoreGeert J P L Kops
Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA
J Cell Biol 169:49-60. 2005..Thus, ZW10 functions as a linker between the core structural elements of the outer kinetochore and components that catalyze generation of the mitotic checkpoint-derived "stop anaphase" inhibitor...
Lethality to human cancer cells through massive chromosome loss by inhibition of the mitotic checkpointGeert J P L Kops
Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093-0670, USA
Proc Natl Acad Sci U S A 101:8699-704. 2004..Thus, suppression of mitotic checkpoint signaling is invariably lethal as the consequence of massive chromosome loss, findings that have implications for inhibiting proliferation of tumor cells...
The forkhead transcription factor FoxO regulates transcription of p27Kip1 and Bim in response to IL-2Marie Stahl
Department of Molecular Biology H8, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
J Immunol 168:5024-31. 2002..Thus, we propose that inactivation of FoxO transcription factors by IL-2 plays a critical role in T cell proliferation and survival...
Cell cycle inhibition by FoxO forkhead transcription factors involves downregulation of cyclin DMarc Schmidt
Division of Molecular Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
Mol Cell Biol 22:7842-52. 2002..Ectopic expression of cyclin D1 can partially overcome FoxO factor-induced cell cycle arrest, demonstrating that downregulation of D-type cyclins represents a physiologically relevant mechanism of FoxO-induced cell cycle inhibition...
