Experts and Doctors on cell cycle proteins in Utrecht, Netherlands


Locale: Utrecht, Netherlands
Topic: cell cycle proteins

Top Publications

  1. Kops G, van der Voet M, van der Voet M, Manak M, van Osch M, Naini S, et al. APC16 is a conserved subunit of the anaphase-promoting complex/cyclosome. J Cell Sci. 2010;123:1623-33 pubmed publisher
    ..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. ..
  2. Medema R, Kops G, Bos J, Burgering B. AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature. 2000;404:782-7 pubmed
    ..We conclude that AFX-like proteins are involved in cell-cycle regulation and that inactivation of these proteins is an important step in oncogenic transformation. ..
  3. Macurek L, Lindqvist A, Voets O, Kool J, Vos H, Medema R. Wip1 phosphatase is associated with chromatin and dephosphorylates gammaH2AX to promote checkpoint inhibition. Oncogene. 2010;29:2281-91 pubmed publisher
    ..Taken together, our data show that Wip1 has an essential role in dephosphorylation of gamma-H2AX to silence the checkpoint and restore chromatin structure once DNA damage is repaired. ..
  4. Janssen A, van der Burg M, Szuhai K, Kops G, Medema R. Chromosome segregation errors as a cause of DNA damage and structural chromosome aberrations. Science. 2011;333:1895-8 pubmed publisher
    ..Our data show that segregation errors can cause translocations and provide insights into the role of whole-chromosome instability in tumorigenesis...
  5. Janssen A, Kops G, Medema R. Elevating the frequency of chromosome mis-segregation as a strategy to kill tumor cells. Proc Natl Acad Sci U S A. 2009;106:19108-13 pubmed publisher
    ..Thus, targeting the mitotic checkpoint and chromosome alignment simultaneously may selectively kill tumor cells by enhancing chromosome mis-segregations. ..
  6. Ratheesh A, Gomez G, Priya R, Verma S, Kovacs E, Jiang K, et al. Centralspindlin and α-catenin regulate Rho signalling at the epithelial zonula adherens. Nat Cell Biol. 2012;14:818-828 pubmed publisher
    ..Thus, a conserved molecular ensemble that governs Rho activation during cytokinesis is used in interphase cells to control the Rho GTPase cycle at the zonula adherens. ..
  7. Macurek L, Lindqvist A, Medema R. Aurora-A and hBora join the game of Polo. Cancer Res. 2009;69:4555-8 pubmed publisher
    ..Such insight is important for the expected utility of small-molecule inhibitors targeting Plk1 or Aurora-A, and it might help us to improve their application. ..
  8. van Nuland R, Smits A, Pallaki P, Jansen P, Vermeulen M, Timmers H. Quantitative dissection and stoichiometry determination of the human SET1/MLL histone methyltransferase complexes. Mol Cell Biol. 2013;33:2067-77 pubmed publisher
    ..Our findings provide a molecular framework for understanding the diversity and abundance of the different SET1/MLL complexes, which together establish the H3K4 methylation landscape in human cells. ..
  9. Jelluma N, Brenkman A, McLeod I, Yates J, Cleveland D, Medema R, et al. Chromosomal instability by inefficient Mps1 auto-activation due to a weakened mitotic checkpoint and lagging chromosomes. PLoS ONE. 2008;3:e2415 pubmed publisher
    ..Two of the causes of CIN are weakened mitotic checkpoint signaling and persistent merotelic attachments that result in lagging chromosomes during anaphase...

More Information


  1. van Balkom B, de Jong O, Smits M, Brummelman J, Den Ouden K, de Bree P, et al. Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells. Blood. 2013;121:3997-4006, S1-15 pubmed publisher
    ..Collectively, our data indicate that endothelial cells release miR-214-containing exosomes to stimulate angiogenesis through the silencing of ataxia telangiectasia mutated in neighboring target cells. ..
  2. Blanco I, Kuchenbaecker K, Cuadras D, Wang X, Barrowdale D, de Garibay G, et al. Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers. PLoS ONE. 2015;10:e0120020 pubmed publisher
    ..Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers. ..
  3. Serralbo O, Perez Perez J, Heidstra R, Scheres B. Non-cell-autonomous rescue of anaphase-promoting complex function revealed by mosaic analysis of HOBBIT, an Arabidopsis CDC27 homolog. Proc Natl Acad Sci U S A. 2006;103:13250-5 pubmed
  4. Hennrich M, Marino F, Groenewold V, Kops G, Mohammed S, Heck A. Universal quantitative kinase assay based on diagonal SCX chromatography and stable isotope dimethyl labeling provides high-definition kinase consensus motifs for PKA and human Mps1. J Proteome Res. 2013;12:2214-24 pubmed publisher
    ..Our generic method, which makes use of proteolytic cell lysates as a source for peptide-substrate libraries, can be implemented for any kinase present in the kinome. ..
  5. Nijboer C, Heijnen C, Groenendaal F, van Bel F, Kavelaars A. Alternate pathways preserve tumor necrosis factor-alpha production after nuclear factor-kappaB inhibition in neonatal cerebral hypoxia-ischemia. Stroke. 2009;40:3362-8 pubmed publisher
    ..Our data indicate that the switch to JNK/AP-1 activation preserves HI-induced TNF-alpha expression and thereby might contribute to the neuroprotective effect of TAT-NBD possibly through a TNF-R2 dependent mechanism. ..
  6. Lindqvist A, de Bruijn M, Macurek L, Bras A, Mensinga A, Bruinsma W, et al. Wip1 confers G2 checkpoint recovery competence by counteracting p53-dependent transcriptional repression. EMBO J. 2009;28:3196-206 pubmed publisher
    ..Our findings uncover Wip1 as a first in class recovery competence gene, and suggest that the principal function of Wip1 in cellular transformation is to retain proliferative capacity in the face of oncogene-induced stress. ..
  7. Kops G. Dividing the goods: co-ordination of chromosome biorientation and mitotic checkpoint signalling by mitotic kinases. Biochem Soc Trans. 2009;37:971-5 pubmed publisher
    ..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. ..
  8. Horree N, van Diest P, van der Groep P, Sie Go D, Heintz A. Progressive derailment of cell cycle regulators in endometrial carcinogenesis. J Clin Pathol. 2008;61:36-42 pubmed
  9. Wolters V, Alizadeh B, Weijerman M, Zhernakova A, van Hoogstraten I, Mearin M, et al. Intestinal barrier gene variants may not explain the increased levels of antigliadin antibodies, suggesting other mechanisms than altered permeability. Hum Immunol. 2010;71:392-6 pubmed publisher
    ..Thus, other immunologic phenomena play a role in the increased prevalence of elevated AGA in patients with Down syndrome, possibly involving altered induction and/or maintenance of tolerance. ..
  10. Winkler G, Mulder K, Bardwell V, Kalkhoven E, Timmers H. Human Ccr4-Not complex is a ligand-dependent repressor of nuclear receptor-mediated transcription. EMBO J. 2006;25:3089-99 pubmed
    ..These findings define a function for the human Ccr4-Not complex as a transcriptional repressor of nuclear receptor signalling that is relevant for the understanding of molecular pathways involved in cancer. ..
  11. Sliedrecht T, Zhang C, Shokat K, Kops G. Chemical genetic inhibition of Mps1 in stable human cell lines reveals novel aspects of Mps1 function in mitosis. PLoS ONE. 2010;5:e10251 pubmed publisher
    ..These cell lines present the best cellular model system to date for investigations into Mps1 biology and the effects of penetrance and duration of Mps1 inhibition on cell viability. ..
  12. Milne A, Leguit R, Corver W, Morsink F, Polak M, de Leng W, et al. Loss of CDC4/FBXW7 in gastric carcinoma. Cell Oncol. 2010;32:347-59 pubmed publisher
    ..Mutations in colonic adenomas, and the frequent losses on 4q described in gastric cancer prompt speculation about the role of CDC4/FBXW7 in gastric carcinogenesis...
  13. Blokhuis A, Groen E, Koppers M, van den Berg L, Pasterkamp R. Protein aggregation in amyotrophic lateral sclerosis. Acta Neuropathol. 2013;125:777-94 pubmed publisher
    ..Further insight into protein aggregation will not only deepen our understanding of ALS pathogenesis but also may provide novel avenues for therapeutic intervention. ..
  14. Schmidt R, Fielmich L, Grigoriev I, Katrukha E, Akhmanova A, van den Heuvel S. Two populations of cytoplasmic dynein contribute to spindle positioning in C. elegans embryos. J Cell Biol. 2017;216:2777-2793 pubmed publisher
  15. Van Wolfswinkel J, Claycomb J, Batista P, Mello C, Berezikov E, Ketting R. CDE-1 affects chromosome segregation through uridylation of CSR-1-bound siRNAs. Cell. 2009;139:135-48 pubmed publisher
    ..The conserved nature of CDE-1 suggests that similar sorting mechanisms may operate in other animals, including mammals. ..
  16. Laoukili J, Stahl M, Medema R. FoxM1: at the crossroads of ageing and cancer. Biochim Biophys Acta. 2007;1775:92-102 pubmed
    ..In this review, several aspects of FoxM1 function will be discussed, as well as their implication in tumorigenesis. ..
  17. van de Weerdt B, Medema R. Polo-like kinases: a team in control of the division. Cell Cycle. 2006;5:853-64 pubmed
    ..In this review, we will focus our attention on human Plk1 and its family members Plk2-4 and the many roles they play during mitosis. Furthermore, we will describe the currently knowledge of the regulation of these functions...
  18. Korzelius J, The I, Ruijtenberg S, Portegijs V, Xu H, Horvitz H, et al. C. elegans MCM-4 is a general DNA replication and checkpoint component with an epidermis-specific requirement for growth and viability. Dev Biol. 2011;350:358-69 pubmed publisher
    ..Thus, C. elegans mcm-4 has conserved functions in DNA replication and replication checkpoint control but also shows unexpected tissue-specific requirements. ..
  19. Avo Santos M, van de Werken C, de Vries M, Jahr H, Vromans M, Laven J, et al. A role for Aurora C in the chromosomal passenger complex during human preimplantation embryo development. Hum Reprod. 2011;26:1868-81 pubmed publisher
    ..Although, the presence of Aurora C in itself may not explain the high chromosome segregation error rate, the data presented here provide novel information regarding possible mechanisms. ..
  20. Jelluma N, Brenkman A, van den Broek N, Cruijsen C, van Osch M, Lens S, et al. Mps1 phosphorylates Borealin to control Aurora B activity and chromosome alignment. Cell. 2008;132:233-46 pubmed publisher
    ..Mps1 thus coordinates attachment error correction and checkpoint signaling, two crucial responses to unproductive chromosome attachments...
  21. Janssen A, Kops G, Medema R. Targeting the mitotic checkpoint to kill tumor cells. Horm Cancer. 2011;2:113-6 pubmed publisher
    ..We demonstrate that increased cell death is associated with a dramatic increase in segregation errors. This suggests that inhibition of the mitotic checkpoint might represent a useful anti-cancer strategy. ..
  22. Jelluma N, Dansen T, Sliedrecht T, Kwiatkowski N, Kops G. Release of Mps1 from kinetochores is crucial for timely anaphase onset. J Cell Biol. 2010;191:281-90 pubmed publisher
    ..We propose that release of Mps1 from kinetochores is essential for mitotic checkpoint silencing and a fast metaphase-to-anaphase transition. ..
  23. Koppers M, van Blitterswijk M, Vlam L, Rowicka P, Van Vught P, Groen E, et al. VCP mutations in familial and sporadic amyotrophic lateral sclerosis. Neurobiol Aging. 2012;33:837.e7-13 pubmed publisher
    ..I114V mutation to be a rare benign polymorphism. VCP mutations are a rare cause of familial ALS. The role of VCP mutations in sporadic ALS, if present, appears limited. ..
  24. Ping Z, Lim R, Bashir T, Pagano M, Guardavaccaro D. APC/C (Cdh1) controls the proteasome-mediated degradation of E2F3 during cell cycle exit. Cell Cycle. 2012;11:1999-2005 pubmed publisher
    ..These findings indicate that the APC/C (Cdh1) ubiquitin ligase targets E2F3 for proteasome-dependent degradation during cell cycle exit and neuronal differentiation. ..
  25. van Leuken R, Clijsters L, van Zon W, Lim D, Yao X, Wolthuis R, et al. Polo-like kinase-1 controls Aurora A destruction by activating APC/C-Cdh1. PLoS ONE. 2009;4:e5282 pubmed publisher
    ..We conclude that Plk1 facilitates efficient Aurora A degradation through APC/C-Cdh1 activation after mitosis, with a potential role for hCdc14A. ..
  26. Van Beekum O, Kalkhoven E. Aberrant forms of histone acetyltransferases in human disease. Subcell Biochem. 2007;41:233-62 pubmed
    ..This seems particularly relevant given the wide range of diseases in which acetyltransferases have been implicated and may help to open up new therapeutic avenues...
  27. Pérez Pérez J, Serralbo O, Vanstraelen M, Gonzalez C, Criqui M, Genschik P, et al. Specialization of CDC27 function in the Arabidopsis thaliana anaphase-promoting complex (APC/C). Plant J. 2008;53:78-89 pubmed
    ..Loss-of-function analysis, as well as cyclin B reporter protein accumulation, indicates a conserved role for the plant APC/C in controlling mitotic progression and cell differentiation during the entire life cycle. ..