cdc2 protein kinase

Summary

Summary: Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.

Top Publications

  1. pmc Global analysis of Cdk1 substrate phosphorylation sites provides insights into evolution
    Liam J Holt
    Departments of Physiology and Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA
    Science 325:1682-6. 2009
  2. ncbi Regulation of the G2/M transition by p53
    W R Taylor
    Department of Molecular Biology, Lerner Research Insititute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Oncogene 20:1803-15. 2001
  3. ncbi Mitotic kinases as regulators of cell division and its checkpoints
    E A Nigg
    Max Planck Institute for Biochemistry, Department of Cell Biology, Am Klopferspitz 18a, D 82152 Martinsried, Germany
    Nat Rev Mol Cell Biol 2:21-32. 2001
  4. pmc Progressive activation of CyclinB1-Cdk1 coordinates entry to mitosis
    Olivier Gavet
    The Gurdon Institute and Department of Zoology, Tennis Court Road, CB2 1QN Cambridge, UK
    Dev Cell 18:533-43. 2010
  5. pmc The decision to enter mitosis: feedback and redundancy in the mitotic entry network
    Arne Lindqvist
    Department of Medical Oncology, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands
    J Cell Biol 185:193-202. 2009
  6. pmc Selective small-molecule inhibitor reveals critical mitotic functions of human CDK1
    Lyubomir T Vassilev
    Departments of Discovery Oncology and Discovery Chemistry, Roche Research Center, Hoffmann La Roche, Inc, Nutley, NJ 07110, USA
    Proc Natl Acad Sci U S A 103:10660-5. 2006
  7. ncbi Greatwall phosphorylates an inhibitor of protein phosphatase 2A that is essential for mitosis
    Satoru Mochida
    Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK
    Science 330:1670-3. 2010
  8. ncbi Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms
    A Satyanarayana
    Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute Frederick, Frederick, MD 21702 1201, USA
    Oncogene 28:2925-39. 2009
  9. ncbi Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5
    L Meijer
    CNRS, Station Biologique, Roscoff, France
    Eur J Biochem 243:527-36. 1997
  10. ncbi Aurora-A and an interacting activator, the LIM protein Ajuba, are required for mitotic commitment in human cells
    Toru Hirota
    Department of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University, Japan
    Cell 114:585-98. 2003

Research Grants

  1. Role of the Y-Located TSPY Gene in Human Oncogenesis
    Yun Fai Chris Lau; Fiscal Year: 2013
  2. Herpesvirus protein kinases: Substrate recognition and pathway targeting.
    S Diane Hayward; Fiscal Year: 2013
  3. The Role of Cks Proteins in Mammalian Meiosis
    Charles H Spruck; Fiscal Year: 2010
  4. G2 Role For Cdk2 in Human Cells
    Gregory Enders; Fiscal Year: 2007
  5. Pathways of Therapy-induced Senescence in Cancer
    Daniel Y Wu; Fiscal Year: 2010
  6. CONTROL OF CELL DIVISION IN FISSION YEAST
    David Beach; Fiscal Year: 1993
  7. CELL CYCLE CONTROL BY THE CAMP PKA SIGNAL TRANSDUCTION P
    Jean Gautier; Fiscal Year: 2002
  8. FUNCTIONS OF SRY AND SRY INTERACTIVE PROTEIN GENES
    Yun Fai Chris Lau; Fiscal Year: 2004
  9. Proteolytic Control of Early Events in Mitosis
    JAMES FERRELL; Fiscal Year: 2008
  10. Effects of Ethanol on Pancreas Regeneration
    Dahn Clemens; Fiscal Year: 2008

Detail Information

Publications315 found, 100 shown here

  1. pmc Global analysis of Cdk1 substrate phosphorylation sites provides insights into evolution
    Liam J Holt
    Departments of Physiology and Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA
    Science 325:1682-6. 2009
    ..The gain or loss of phosphorylation sites in rapidly evolving regions could facilitate the evolution of kinase-signaling circuits...
  2. ncbi Regulation of the G2/M transition by p53
    W R Taylor
    Department of Molecular Biology, Lerner Research Insititute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Oncogene 20:1803-15. 2001
    ..In summary, multiple overlapping p53-dependent and p53-independent pathways regulate the G2/M transition in response to genotoxic stress...
  3. ncbi Mitotic kinases as regulators of cell division and its checkpoints
    E A Nigg
    Max Planck Institute for Biochemistry, Department of Cell Biology, Am Klopferspitz 18a, D 82152 Martinsried, Germany
    Nat Rev Mol Cell Biol 2:21-32. 2001
    ..Here, I give an overview of the many mitotic kinases that regulate cell division and the fidelity of chromosome transmission...
  4. pmc Progressive activation of CyclinB1-Cdk1 coordinates entry to mitosis
    Olivier Gavet
    The Gurdon Institute and Department of Zoology, Tennis Court Road, CB2 1QN Cambridge, UK
    Dev Cell 18:533-43. 2010
    ....
  5. pmc The decision to enter mitosis: feedback and redundancy in the mitotic entry network
    Arne Lindqvist
    Department of Medical Oncology, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands
    J Cell Biol 185:193-202. 2009
    ....
  6. pmc Selective small-molecule inhibitor reveals critical mitotic functions of human CDK1
    Lyubomir T Vassilev
    Departments of Discovery Oncology and Discovery Chemistry, Roche Research Center, Hoffmann La Roche, Inc, Nutley, NJ 07110, USA
    Proc Natl Acad Sci U S A 103:10660-5. 2006
    ..Although CDK1 inhibition for up to 24 h is well tolerated, longer exposure to the inhibitor induces apoptosis in tumor cells, suggesting that selective CDK1 inhibitors may have utility in cancer therapy...
  7. ncbi Greatwall phosphorylates an inhibitor of protein phosphatase 2A that is essential for mitosis
    Satoru Mochida
    Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK
    Science 330:1670-3. 2010
    ..This converts Ensa into a potent and specific inhibitor of PP2A-B55δ. This pathway represents a previously unknown element in the control of mitosis...
  8. ncbi Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms
    A Satyanarayana
    Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute Frederick, Frederick, MD 21702 1201, USA
    Oncogene 28:2925-39. 2009
    ..Nevertheless, cell-cycle-independent functions of Cdks and cyclins such as in DNA damage repair are still under investigation. Here we review the compensatory mechanisms among major cyclins and Cdks in mammalian cell-cycle regulation...
  9. ncbi Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5
    L Meijer
    CNRS, Station Biologique, Roscoff, France
    Eur J Biochem 243:527-36. 1997
    ..Through its unique selectivity for some cyclin-dependent kinases, roscovitine provides a useful antimitotic reagent for cell cycle studies and may prove interesting to control cells with deregulated cdc2, cdk2 or cdk5 kinase activities...
  10. ncbi Aurora-A and an interacting activator, the LIM protein Ajuba, are required for mitotic commitment in human cells
    Toru Hirota
    Department of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University, Japan
    Cell 114:585-98. 2003
    ..Depletion of Ajuba prevented activation of Aurora-A at centrosomes in late G2 phase and inhibited mitotic entry. Overall, our data suggest that Ajuba is an essential activator of Aurora-A in mitotic commitment...
  11. ncbi Substrate competition as a source of ultrasensitivity in the inactivation of Wee1
    Sun Young Kim
    Department of Chemical and Systems Biology, Stanford University School of Medicine, Center for Clinical Sciences Research, Stanford, CA 94305 5174, USA
    Cell 128:1133-45. 2007
    ..Based on these findings, we were able to reconstitute a highly ultrasensitive Wee1 response with purified components. Competition provides a simple way of generating the equivalent of a highly cooperative allosteric response...
  12. ncbi Phosphatases: providing safe passage through mitotic exit
    Claudia Wurzenberger
    Institute of Biochemistry, Department of Biology, Swiss Federal Institute of Technology Zurich ETHZ, HPM D11 3, Schafmattstrasse 18, 8093 Zurich, Switzerland
    Nat Rev Mol Cell Biol 12:469-82. 2011
    ..The key mitotic exit phosphatase in budding yeast, Cdc14, is now well understood. By contrast, in animal cells, it is now emerging that mitotic exit relies on distinct regulatory networks, including the protein phosphatases PP1 and PP2A...
  13. ncbi Cdk1 is sufficient to drive the mammalian cell cycle
    David Santamaria
    Molecular Oncology Programme, Centro Nacional de Investigaciones Oncologicas, E 28029 Madrid, Spain
    Nature 448:811-5. 2007
    ..These results indicate that Cdk1 is the only essential cell cycle Cdk. Moreover, they show that in the absence of interphase Cdks, Cdk1 can execute all the events that are required to drive cell division...
  14. pmc CDK1-dependent phosphorylation of EZH2 suppresses methylation of H3K27 and promotes osteogenic differentiation of human mesenchymal stem cells
    Yongkun Wei
    Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Nat Cell Biol 13:87-94. 2011
    ..These findings define a signalling link between CDK1 and EZH2 that may have an important role in diverse biological processes, including cancer-cell invasion and osteogenic differentiation of mesenchymal stem cells...
  15. ncbi Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis
    H Zou
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Science 285:418-22. 1999
    ..The oncogenic nature of increased expression of vSecurin may result from chromosome gain or loss, produced by errors in chromatid separation...
  16. pmc Bora and the kinase Aurora a cooperatively activate the kinase Plk1 and control mitotic entry
    Akiko Seki
    Department of Biological Sciences, Stanford University, Stanford, CA 94305 5020, USA
    Science 320:1655-8. 2008
    ..Thus, Bora and Aur-A control mitotic entry, which provides a mechanism for one of the most important yet ill-defined events in the cell cycle...
  17. ncbi Identification of essential genes in cultured mammalian cells using small interfering RNAs
    J Harborth
    Department of Biochemistry and Cell Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, , Germany
    J Cell Sci 114:4557-65. 2001
    ..Interestingly the inner nuclear membrane protein emerin, thought to be a ligand of lamin A/C, is also a nonessential protein in tissue culture cells...
  18. ncbi Myt1: a membrane-associated inhibitory kinase that phosphorylates Cdc2 on both threonine-14 and tyrosine-15
    P R Mueller
    Division of Biology 216 76, Howard Hughes Medical Institute, California Institute of Technology, Pasadena 91125, USA
    Science 270:86-90. 1995
    ..Myt1 activity is highly regulated during the cell cycle, suggesting that this relative of Wee1 plays a role in mitotic control...
  19. ncbi MASTL is the human orthologue of Greatwall kinase that facilitates mitotic entry, anaphase and cytokinesis
    Erik Voets
    Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Cell Cycle 9:3591-601. 2010
    ..We propose that MASTL enhances cyclin B1-Cdk1-dependent mitotic phosphorylation events, directing mitotic entry, anaphase and cytokinesis in human cells...
  20. pmc Phosphorylation of Mcl-1 by CDK1-cyclin B1 initiates its Cdc20-dependent destruction during mitotic arrest
    Margaret E Harley
    Biomedical Research Institute, School of Medicine, College of Medicine, Dentistry and Nursing, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, UK
    EMBO J 29:2407-20. 2010
    ..Regulation of apoptosis, therefore, is linked intrinsically to progression through mitosis and is governed by a temporal mechanism that distinguishes between normal mitosis and prolonged mitotic arrest...
  21. pmc The overlooked greatwall: a new perspective on mitotic control
    David M Glover
    Department of Genetics, University of Cambridge, Downing Street, Cambridge CB3 9JW, UK
    Open Biol 2:120023. 2012
    ..I discuss how these alternating states of preferential PP2A-B55 or Cdk1-CycB activity can have an impact upon the regulation of Polo kinase and its ability to bind different partner proteins as mitosis progresses...
  22. ncbi Dual inhibition of sister chromatid separation at metaphase
    O Stemmann
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 107:715-26. 2001
    ..We propose that separase activation at the metaphase-anaphase transition requires the removal of both securin and an inhibitory phosphate...
  23. pmc Cyclin A is required at two points in the human cell cycle
    M Pagano
    Differentiation, Programme European Molecular Biology Laboratory, Heidelberg, Germany
    EMBO J 11:961-71. 1992
    ..Cyclin A binds both cdk2 and cdc2, giving two distinct cyclin A kinase activities, one appearing in S phase, the other in G2. These results suggest that cyclin A defines novel control points of the human cell cycle...
  24. pmc Human cyclins A and B1 are differentially located in the cell and undergo cell cycle-dependent nuclear transport
    J Pines
    Molecular Biology and Virology Laboratory, Salk Institute for Biological Studies, San Diego, California 92186 5800
    J Cell Biol 115:1-17. 1991
    ....
  25. pmc A mitotic phosphorylation feedback network connects Cdk1, Plk1, 53BP1, and Chk2 to inactivate the G(2)/M DNA damage checkpoint
    Marcel A T M van Vugt
    David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    PLoS Biol 8:e1000287. 2010
    ....
  26. ncbi Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability
    James E Ferrell
    Department of Molecular Pharmacology, CCSR, 269 Campus Drive, Stanford University School of Medicine, Stanford, CA 94305 5174, USA
    Curr Opin Cell Biol 14:140-8. 2002
    ..Here we review the basic properties of bistable circuits, the requirements for construction of a satisfactory bistable switch, and the recent progress towards constructing and analysing bistable signaling systems...
  27. pmc Rereplication by depletion of geminin is seen regardless of p53 status and activates a G2/M checkpoint
    Wenge Zhu
    Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
    Mol Cell Biol 24:7140-50. 2004
    ..From these results, we conclude that geminin is required for suppressing overreplication in human cells and that a G(2)/M checkpoint restricts the proliferation of cells with overreplicated DNA...
  28. ncbi Phosphorylation of the CPC by Cdk1 promotes chromosome bi-orientation
    Tatsuya Tsukahara
    Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113 0032, Japan
    Nature 467:719-23. 2010
    ..In human cells, the phosphorylation of Borealin has a comparable role. Thus, our study resolves the conserved mechanisms of CPC targeting to centromeres, highlighting a key role of Cdk1-cyclin B in chromosome bi-orientation...
  29. pmc Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis
    David T Terrano
    Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 7199, USA
    Mol Cell Biol 30:640-56. 2010
    ..Thus, phosphorylation of antiapoptotic Bcl-2 proteins acts as a sensor for CDK1 signal duration and as a functional link coupling mitotic arrest to apoptosis...
  30. ncbi Targeting mitotic exit leads to tumor regression in vivo: Modulation by Cdk1, Mastl, and the PP2A/B55α,δ phosphatase
    Eusebio Manchado
    Spanish National Cancer Research Centre, Madrid, Spain
    Cancer Cell 18:641-54. 2010
    ..These data illustrate the relevance of critical players of mitotic exit in mammals and their implications in the balance between cell death and mitotic exit in tumor cells...
  31. ncbi From Cdc2 to Cdk1: when did the cell cycle kinase join its cyclin partner?
    Marcel Doree
    CRBM, UPR 1086 CNRS, 1919 Route de Mende, 34293 Montpellier Cedex 5, France
    J Cell Sci 115:2461-4. 2002
    ..When this fundamental discovery was confirmed in vertebrates and mammalian members of the Cdc2 family were also shown to bind cyclins, Cdc2 became Cdk1, the first cyclin-dependent protein kinase...
  32. ncbi Phosphorylation of Nup98 by multiple kinases is crucial for NPC disassembly during mitotic entry
    Eva Laurell
    Institute of Biochemistry, ETH Zurich, Switzerland
    Cell 144:539-50. 2011
    ..Together, our data provide evidence for a phosphorylation-dependent mechanism underlying disintegration of NPCs during prophase. Moreover, we identify mitotic phosphorylation of Nup98 as a rate-limiting step in mitotic NPC disassembly...
  33. ncbi Partial nuclear pore complex disassembly during closed mitosis in Aspergillus nidulans
    Colin P C De Souza
    Department of Molecular Genetics, Ohio State University, Columbus, Ohio 43210, USA
    Curr Biol 14:1973-84. 2004
    ..Therefore, we wished to define the mechanism by which the NPC is regulated during A. nidulans' closed mitosis...
  34. ncbi TOR signalling regulates mitotic commitment through the stress MAP kinase pathway and the Polo and Cdc2 kinases
    Janni Petersen
    The Rockefeller University, Box 5, 1230 York Avenue, New York, NY 10021, USA
    Nat Cell Biol 9:1263-72. 2007
    ..Therefore, TOR signalling modulates mitotic onset through the stress MAPK pathway via the Pyp2 phosphatase...
  35. ncbi Distinct roles for cyclin-dependent kinases in cell cycle control
    S van den Heuvel
    Massachusetts General Hospital Cancer Center, Charlestown 02129
    Science 262:2050-4. 1993
    ..The mutant phenotypes were specifically rescued by the corresponding wild-type kinases. These data reveal that Cdk3, in addition to Cdc2 and Cdk2, executes a distinct and essential function in the mammalian cell cycle...
  36. ncbi Systems-level dissection of the cell-cycle oscillator: bypassing positive feedback produces damped oscillations
    Joseph R Pomerening
    Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305, USA
    Cell 122:565-78. 2005
    ..This work also underscores the fundamental similarity of cell-cycle oscillations in embryos to repetitive action potentials in pacemaker neurons, with both systems relying on a combination of negative and positive-feedback loops...
  37. pmc Switches and latches: a biochemical tug-of-war between the kinases and phosphatases that control mitosis
    Maria Rosa Domingo-Sananes
    Department of Biochemistry, Oxford Centre for Integrative Systems Biology, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
    Philos Trans R Soc Lond B Biol Sci 366:3584-94. 2011
    ..The bistable character of the switch implies the existence of a CycB threshold for entry into mitosis. The end of G2 phase is determined by the point where CycB level crosses the CycB threshold for Cdk1 activation...
  38. pmc Differential control of Eg5-dependent centrosome separation by Plk1 and Cdk1
    Ewan Smith
    Genome Damage and Stability Centre, University of Sussex, Brighton, UK
    EMBO J 30:2233-45. 2011
    ..Conversely, MT stabilization in mitosis slows down Cdk1-dependent centrosome movement. Our findings implicate the modulation of MT stability in G2 and M phase as a regulatory element in the control of centrosome separation...
  39. pmc Quantitative phosphoproteomics identifies substrates and functional modules of Aurora and Polo-like kinase activities in mitotic cells
    Arminja N Kettenbach
    Department of Genetics, Dartmouth Medical School, Lebanon, NH 03756, USA
    Sci Signal 4:rs5. 2011
    ....
  40. pmc Mitotic progression becomes irreversible in prometaphase and collapses when Wee1 and Cdc25 are inhibited
    Tamara A Potapova
    Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
    Mol Biol Cell 22:1191-206. 2011
    ..These findings suggest that the positive feedback in Cdk activation serves to overcome the activity of Cdk-opposing phosphatases and thus sustains forward progression in mitosis...
  41. ncbi CDK1 inhibitors antagonize the immediate apoptosis triggered by spindle disruption but promote apoptosis following the subsequent rereplication and abnormal mitosis
    Ying Wai Chan
    Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong
    Cell Cycle 7:1449-61. 2008
    ..These data underscore the essential role of cyclin B1-CDK1 as the basis of apoptosis during mitotic arrest, and the role of mitotic slippage and abnormal mitosis for apoptosis at later stages...
  42. ncbi Greatwall kinase participates in the Cdc2 autoregulatory loop in Xenopus egg extracts
    Jiangtao Yu
    Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA
    Mol Cell 22:83-91. 2006
    ..These results demonstrate that Greatwall participates in an autoregulatory loop that generates and maintains sufficiently high MPF activity levels to support mitosis...
  43. pmc Systematic discovery of in vivo phosphorylation networks
    Rune Linding
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada
    Cell 129:1415-26. 2007
    ..Applying this approach to DNA damage signaling, we show that 53BP1 and Rad50 are phosphorylated by CDK1 and ATM, respectively. We describe a scalable strategy to evaluate predictions, which suggests that BCLAF1 is a GSK-3 substrate...
  44. ncbi Isolation of a human cyclin cDNA: evidence for cyclin mRNA and protein regulation in the cell cycle and for interaction with p34cdc2
    J Pines
    Molecular Biology and Virology Laboratory, Salk Institute for Biological Studies, San Diego, California 92138
    Cell 58:833-46. 1989
    ..In G2/M phase, cyclin is associated with p34cdc2, the human homolog of the fission yeast gene cdc2+, and this complex has histone H1 kinase activity...
  45. pmc Covalent capture of kinase-specific phosphopeptides reveals Cdk1-cyclin B substrates
    Justin D Blethrow
    Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA
    Proc Natl Acad Sci U S A 105:1442-7. 2008
    ..This approach has the potential to expand our understanding of kinase-substrate connections in signaling networks...
  46. ncbi Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis
    K L Gould
    Department of Biochemistry, University of Oxford, UK
    Nature 342:39-45. 1989
    ..Substitution of this tyrosine by phenylalanine advances cells prematurely into mitosis, establishing that tyrosine phosphorylation/dephosphorylation directly regulates pp34 function...
  47. pmc Fine tuning the cell cycle: activation of the Cdk1 inhibitory phosphorylation pathway during mitotic exit
    Tamara A Potapova
    Cell Cycle and Cancer Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
    Mol Biol Cell 20:1737-48. 2009
    ..This late Cdk1 reactivation often results in caspase-dependent cell death. Thus, in G1, the Cdk inhibitory phosphorylation pathway is functional and can lock Cdk1 in the inactive state...
  48. pmc Forkhead box M1B transcriptional activity requires binding of Cdk-cyclin complexes for phosphorylation-dependent recruitment of p300/CBP coactivators
    Michael L Major
    Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    Mol Cell Biol 24:2649-61. 2004
    ....
  49. ncbi Cdk1 negatively regulates midzone localization of the mitotic kinesin Mklp2 and the chromosomal passenger complex
    Stefan Hümmer
    Department of Biology and Konstanz Research School Chemical Biology, University of Konstanz, 78457 Konstanz, Germany
    Curr Biol 19:607-12. 2009
    ..Collectively, our data suggest that anaphase onset triggers the association between the CPC and Mklp2 and that this association targets the CPC-Mklp2 complex to the ends of stable microtubules in the spindle midzone...
  50. ncbi Constant regulation of both the MPF amplification loop and the Greatwall-PP2A pathway is required for metaphase II arrest and correct entry into the first embryonic cell cycle
    Thierry Lorca
    Universités Montpellier 2 et 1, Centre de Recherche de Biochimie Macromoleculaire, CNRS UMR 5237, IFR 122, 1919 Route de Mende, 34293 Montpellier Cedex 5, France
    J Cell Sci 123:2281-91. 2010
    ....
  51. pmc Cell cycle-dependent dynamics and regulation of mitotic kinesins in Drosophila S2 cells
    Gohta Goshima
    The Howard Hughes Medical Institute and the Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94107, USA
    Mol Biol Cell 16:3896-907. 2005
    ..These results reveal a diverse spectrum of regulatory mechanisms for controlling the localization and function of five mitotic kinesins at different stages of the cell cycle...
  52. pmc Robust, tunable biological oscillations from interlinked positive and negative feedback loops
    Tony Yu Chen Tsai
    Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305 5174, USA
    Science 321:126-9. 2008
    ..Positive-plus-negative oscillators also appear to be more robust and easier to evolve, rationalizing why they are found in contexts where an adjustable frequency is unimportant...
  53. pmc A phosphatase threshold sets the level of Cdk1 activity in early mitosis in budding yeast
    Stacy L Harvey
    Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
    Mol Biol Cell 22:3595-608. 2011
    ..These results define a new role for PP2A(Cdc55) and reveal a systems-level mechanism by which dynamically opposed kinase and phosphatase activities can modulate signal strength...
  54. pmc p107wee1 is a dual-specificity kinase that phosphorylates p34cdc2 on tyrosine 15
    L L Parker
    Department of Physiology, Tufts University School of Medicine, Boston, MA 02111
    Proc Natl Acad Sci U S A 89:2917-21. 1992
    ..These results indicate that p107wee1 functions as a mitotic inhibitor by directly phosphorylating p34cdc2 on Tyr-15 and that the preferred substrate for phosphorylation is the p34cdc2/cyclin complex...
  55. ncbi Radiosensitization of p53 mutant cells by PD0166285, a novel G(2) checkpoint abrogator
    Y Wang
    Department of Cancer Molecular Sciences, Pfizer Global Research and Development, Ann Arbor Laboratories, 2800 Plymouth Road, Ann Arbor, MI 48105, USA
    Cancer Res 61:8211-7. 2001
    ..Thus, G(2) checkpoint abrogators represent a novel class of anticancer drugs that enhance cell killing of conventional cancer therapy through the induction of premature mitosis...
  56. pmc Spatial positive feedback at the onset of mitosis
    Silvia D M Santos
    Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305 5174, USA
    Cell 149:1500-13. 2012
    ..We propose that spatial positive feedback ensures a rapid, complete, robust, and irreversible transition from interphase to mitosis and suggest that bistable spatiotemporal switches may be widespread in biological regulation...
  57. pmc Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2
    Shuai Chen
    Masonic Cancer Center, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, USA
    Nat Cell Biol 12:1108-14. 2010
    ..These results demonstrate that CDK-mediated phosphorylation is a key mechanism governing EZH2 function and that there is a link between the cell-cycle machinery and epigenetic gene silencing...
  58. ncbi Cdc2 phosphorylation of BAD links the cell cycle to the cell death machinery
    Yoshiyuki Konishi
    Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Mol Cell 9:1005-16. 2002
    ..Our results suggest that a critical component of the cell cycle couples an apoptotic signal to the cell death machinery via a phosphorylation-dependent mechanism that may generally modulate protein-protein interactions...
  59. ncbi Stable association of mitotic cyclin B/Cdc2 to replication origins prevents endoreduplication
    Jérôme Wuarin
    Division of Yeast Genetics, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom
    Cell 111:419-31. 2002
    ..Thus, ORC bound mitotic Cyclin B/Cdc2 kinase imposes the dependency of S phase on an intervening mitosis but not the temporal licensing of replication origins between each S phase...
  60. pmc Budding yeast greatwall and endosulfines control activity and spatial regulation of PP2A(Cdc55) for timely mitotic progression
    María Angeles Juanes
    Centre de Recherche en Biochimie Macromoleculaire, Montpellier, France
    PLoS Genet 9:e1003575. 2013
    ..However, this conserved module is adapted to account for differences in the regulation of mitotic entry in different organisms. ..
  61. ncbi Analysis of the early embryonic cell cycles of Xenopus; regulation of cell cycle length by Xe-wee1 and Mos
    M S Murakami
    ABL Basic Research Program, NCI Frederick Cancer Research and Development Center, MD 21702, USA
    Development 125:237-48. 1998
    ..Our experiments indicate that Mos/MAPK can also contribute to cell cycle length...
  62. pmc The BEG (PP2A-B55/ENSA/Greatwall) pathway ensures cytokinesis follows chromosome separation
    Michael J Cundell
    University of Oxford, Department of Biochemistry, South Parks Road, Oxford OX1 3QU, UK
    Mol Cell 52:393-405. 2013
    ..Therefore, temporal order during mitotic exit is promoted by the metazoan BEG pathway. ..
  63. pmc Laser microsurgery provides evidence for merotelic kinetochore attachments in fission yeast cells lacking Pcs1 or Clr4
    Cornelia Rumpf
    Max F Perutz Laboratories, University of Vienna, Vienna, Austria
    Cell Cycle 9:3997-4004. 2010
    ..Finally, we show that Pcs1/Mde4 complex shares similar features with the conserved kinetochore complex Spc24/Spc25 suggesting that these two complexes may occupy a similar functional niche...
  64. ncbi Dephosphorylation and activation of a p34cdc2/cyclin B complex in vitro by human CDC25 protein
    U Strausfeld
    CNRS and INSERM, BP 5051, Montpellier, France
    Nature 351:242-5. 1991
    ..We propose that the cdc25+ gene product directly activates the p34cdc2-cyclin B complex...
  65. pmc A novel role for greatwall kinase in recovery from DNA damage
    Aimin Peng
    Howard Hughes Medical Institute, Department of Pharmacology, University of Colorado School of Medicine, Aurora, USA
    Cell Cycle 9:4364-9. 2010
    ..Moreover, activation of Cdk1 after the removal of damaged DNA is regulated by Gwl. Collectively, these results defines Gwl as a new regulator of the DDR, which plays an important role in recovery from DNA damage...
  66. pmc Cell cycle regulation of a Xenopus Wee1-like kinase
    P R Mueller
    Division of Biology 216 76, Howard Hughes Medical Institute, California Institute of Technology, Pasadena 91125, USA
    Mol Biol Cell 6:119-34. 1995
    ..These studies indicate that the down-regulation of Wee1-like kinase activity at mitosis is a multistep process that occurs after other biochemical reactions have signaled the successful completion of S phase...
  67. pmc Killing cells by targeting mitosis
    E Manchado
    Cell Division and Cancer Group, Spanish National Cancer Research Center, Madrid, Spain
    Cell Death Differ 19:369-77. 2012
    ..As the efficacy of cell-cycle targeting approaches has been limited so far, further understanding of the molecular pathways modulating mitotic cell death will be required to move forward these new proposals to the clinic...
  68. pmc Differential phosphorylation of vertebrate p34cdc2 kinase at the G1/S and G2/M transitions of the cell cycle: identification of major phosphorylation sites
    W Krek
    Swiss Institute for Experimental Cancer Research, ISREC, Epalinges
    EMBO J 10:305-16. 1991
    ....
  69. ncbi Polo-like kinases: a team that plays throughout mitosis
    D M Glover
    Department of Anatomy and Physiology, Medical Sciences Institute, University of Dundee, UK
    Genes Dev 12:3777-87. 1998
  70. ncbi Asymmetric recruitment of dynein to spindle poles and microtubules promotes proper spindle orientation in yeast
    Sandrine Grava
    Institute of Biochemistry, Biology Department, Swiss Federal Institute of Technology, ETH Zurich, 8093 Zurich, Switzerland
    Dev Cell 10:425-39. 2006
    ..Together, our data indicate that proper orientation of the spindle requires dynein to act on a single spindle pole...
  71. ncbi Cyclin B1 and CDK1: nuclear localization and upstream regulators
    Lisa A Porter
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093 0367, USA
    Prog Cell Cycle Res 5:335-47. 2003
    ..Elucidating the role of mediators controlling cyclin B1-CDK1 translocation at the onset of mitosis is essential in developing drug targets for cell cycle control...
  72. pmc A novel p34(cdc2)-binding and activating protein that is necessary and sufficient to trigger G(2)/M progression in Xenopus oocytes
    I Ferby
    European Molecular Biology Laboratory, 69117 Heidelberg, Germany
    Genes Dev 13:2177-89. 1999
    ..Our results identify a novel p34(cdc2) binding and activating protein that regulates the G(2)/M transition during oocyte maturation...
  73. ncbi Mitotic phosphatases: from entry guards to exit guides
    Mathieu Bollen
    Laboratory of Biosignaling and Therapeutics, Department of Molecular Cell Biology, University of Leuven, B 3000 Leuven, Belgium
    Trends Cell Biol 19:531-41. 2009
    ..These new findings show that protein phosphatases regulate every step of mitosis and provide novel insights into the dynamic and versatile nature of mitotic phosphoregulation...
  74. pmc Control of cell proliferation, organ growth, and DNA damage response operate independently of dephosphorylation of the Arabidopsis Cdk1 homolog CDKA;1
    Nico Dissmeyer
    Unigruppe am Max Planck Institut für Züchtungsforschung, Max Delbrück Laboratorium, Lehrstuhl für Botanik III, Universitat zu Koln, Koln, Germany
    Plant Cell 21:3641-54. 2009
    ..Based on biomathematical simulations, we propose a plant-specific model of how progression through the cell cycle could be wired in Arabidopsis...
  75. ncbi Activation of FOXO1 by Cdk1 in cycling cells and postmitotic neurons
    Zengqiang Yuan
    Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Science 319:1665-8. 2008
    ..These findings define a conserved signaling link between Cdk1 and FOXO1 that may have a key role in diverse biological processes, including the degeneration of postmitotic neurons...
  76. ncbi Identification of nuclear beta II protein kinase C as a mitotic lamin kinase
    V L Goss
    Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106
    J Biol Chem 269:19074-80. 1994
    ....
  77. ncbi Chromosome condensation by a human condensin complex in Xenopus egg extracts
    K Kimura
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    J Biol Chem 276:5417-20. 2001
    ..Thus, the structure and function of the condensin complex are highly conserved between Xenopus and humans, underscoring its fundamental importance in mitotic chromosome dynamics in eukaryotic cells...
  78. ncbi Cyclin B1 depletion inhibits proliferation and induces apoptosis in human tumor cells
    Juping Yuan
    Department of Gynaecology and Obstetrics, Medical School, JW Goethe University, Theodor Stern Kai 7, D 60590 Frankfurt, Germany
    Oncogene 23:5843-52. 2004
    ..These results indicate that siRNAs against cyclin B1 could become a powerful antiproliferative tool in future antitumor therapy...
  79. pmc Activation of Cdc2/cyclin B and inhibition of centrosome amplification in cells depleted of Plk1 by siRNA
    Xiaoqi Liu
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 99:8672-6. 2002
    ..We find that Plk1 depletion results in elevated Cdc2 protein kinase activity and thus attenuates cell-cycle progression...
  80. ncbi The cdc25 protein contains an intrinsic phosphatase activity
    W G Dunphy
    Division of Biology, California Institute of Technology, Pasadena 91125
    Cell 67:189-96. 1991
    ..that the cdc25 protein controls the entry into mitosis by triggering tyrosine dephosphorylation of the cdc2 protein kinase. We show that the isolated cdc25 protein can catalyze dephosphorylation of several model phosphatase ..
  81. pmc A single fission yeast mitotic cyclin B p34cdc2 kinase promotes both S-phase and mitosis in the absence of G1 cyclins
    D L Fisher
    Cell Cycle Laboratory, Imperial Cancer Research Fund, London, UK
    EMBO J 15:850-60. 1996
    ....
  82. ncbi Inhibition of CDK1 as a potential therapy for tumors over-expressing MYC
    Andrei Goga
    Department of Medicine, Division of Hematology Oncology, University of California, San Francisco, San Francisco, California 94143 0552, USA
    Nat Med 13:820-7. 2007
    ..As there are no effective small-molecule inhibitors that selectively target the MYC pathway, we propose that CDK1 inhibition might therefore be useful in the treatment of human malignancies that overexpress MYC...
  83. ncbi Activation of cdc2 protein kinase during mitosis in human cells: cell cycle-dependent phosphorylation and subunit rearrangement
    G Draetta
    Cold Spring Harbor Laboratory, New York 11724
    Cell 54:17-26. 1988
    ..p34 may act to regulate the G2/M transition in HeLa cells...
  84. ncbi Regulation of yeast forkhead transcription factors and FoxM1 by cyclin-dependent and polo-like kinases
    Hiroshi Murakami
    Department of Biochemistry and Cell Biology, Graduate School of Medicine, Nagoya City University, Nagoya, Japan
    Cell Cycle 9:3233-42. 2010
    ....
  85. ncbi Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase
    L L Parker
    Department of Physiology, Tufts University School of Medicine, Boston, MA 02111
    Science 257:1955-7. 1992
    ..These results indicate that the product of the WEE1Hu gene directly regulates the p34cdc2-cyclin B complex in human cells and that a kinase other than that encoded by WEE1Hu phosphorylates p34cdc2 on threonine 14...
  86. ncbi Akt inhibits Myt1 in the signalling pathway that leads to meiotic G2/M-phase transition
    Eiichi Okumura
    Laboratory of Cell and Developmental Biology, Graduate School of Bioscience, Tokyo Institute of Technology, Nagatsuta, Midoriku, Yokohama 226 8501, Japan
    Nat Cell Biol 4:111-6. 2002
    ..These findings identify Myt1 as a new target of Akt, and demonstrate that Akt functions as an M-phase initiator...
  87. ncbi Identification of plectin as a substrate of p34cdc2 kinase and mapping of a single phosphorylation site
    N Malecz
    Institute of Biochemistry and Molecular Cell Biology, University of Vienna, Biocenter, Dr Bohrgasse 9, A 1030 Vienna, Austria
    J Biol Chem 271:8203-8. 1996
    ..Protein kinase A, phosphorylating plectin also within repeat 6, targeted sites that were clearly different from those of p34cdc2 kinase...
  88. pmc Dynamics of Cdk1 substrate specificity during the cell cycle
    Mardo Kõivomägi
    Institute of Technology, University of Tartu, Tartu 50411, Estonia
    Mol Cell 42:610-23. 2011
    ..Finally, we identified several Cln2-, Clb3-, and Clb2-specific Cdk1 targets. We propose that robust timing and ordering of cell cycle events depend on gradual changes in the substrate specificity of Cdk1...
  89. ncbi The Cdk1 complex plays a prime role in regulating N-myc phosphorylation and turnover in neural precursors
    Sarah K Sjostrom
    Department of Pediatric Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA
    Dev Cell 9:327-38. 2005
    ..These findings provide a mechanism for promoting growth arrest in the final cycle of neural precursor proliferation competency, or for resetting the cell cycle in the G1 phase, by destabilizing N-myc in mitosis...
  90. ncbi Apigenin inhibits growth and induces G2/M arrest by modulating cyclin-CDK regulators and ERK MAP kinase activation in breast carcinoma cells
    F Yin
    Division of Endocrinology, UCLA School of Medicine, Los Angeles, California 90024, USA
    Anticancer Res 21:413-20. 2001
    ..These results suggest that apigenin is a promising antibreast cancer agent and its growth inhibitory effects are mediated by targeting different signal transduction pathways in MCF-7 and MDA-MB-468 breast carcinoma cells...
  91. ncbi Identification and comparative analysis of multiple mammalian Speedy/Ringo proteins
    Aiyang Cheng
    Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut, USA
    Cell Cycle 4:155-65. 2005
    ..The existence of this growing family of CDK activators suggests that Speedy/Ringo proteins may play as complex a role in cell cycle control as the diverse family of cyclins...
  92. pmc Interaction of Sororin protein with polo-like kinase 1 mediates resolution of chromosomal arm cohesion
    Nenggang Zhang
    Texas Children s Cancer and Hematology Center, Department of Pediatric Hematology Oncology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 286:41826-37. 2011
    ....
  93. pmc The initial phase of chromosome condensation requires Cdk1-mediated phosphorylation of the CAP-D3 subunit of condensin II
    Satoshi Abe
    Cancer Institute, Japanese Foundation for Cancer Research JFCR, Tokyo 135 8550, Japan
    Genes Dev 25:863-74. 2011
    ..These observations provide an explanation for how Cdk1 induces chromosome assembly in cells entering mitosis, and underscore the significance of the cooperative action of Plk1 with Cdk1...
  94. ncbi Ionizing radiation induces rapid tyrosine phosphorylation of p34cdc2
    S Kharbanda
    Division of Cancer Pharmacology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115
    Cancer Res 54:1412-4. 1994
    ..Since p34cdc2 is required for entry into mitosis, these findings support the posttranslational modification of a cell cycle regulatory protein in the response to ionizing radiation...
  95. ncbi Regulation of mitotic function of Chk1 through phosphorylation at novel sites by cyclin-dependent kinase 1 (Cdk1)
    Takashi Shiromizu
    Division of Biochemistry, Aichi Cancer Center Research Institute, Nagoya, Aichi 464 8681, Japan
    Genes Cells 11:477-85. 2006
    ..These observations imply the regulation of mitotic Chk1 function through Chk1 phosphorylation at novel sites by Cdk1...
  96. pmc Cell cycle regulation of human WEE1
    C H McGowan
    Department of Molecular, Scripps Research Institute, La Jolla, CA 92037, USA
    EMBO J 14:2166-75. 1995
    ..M phase WEE1 is re-activated in samples prepared in the absence of protein phosphatase inhibitors, demonstrating that WEE1 is inhibited by a mechanism that requires protein phosphorylation...
  97. ncbi Purified maturation-promoting factor contains the product of a Xenopus homolog of the fission yeast cell cycle control gene cdc2+
    J Gautier
    Department of Pharmacology, University of Colorado School of Medicine, Denver 80262
    Cell 54:433-9. 1988
    ..These findings indicate that a Xenopus p34cdc2 homolog is present in purified MPF and suggest that p34cdc2 is a component of the control mechanism initiating mitosis generally in eukaryotic cells...
  98. pmc The localization and phosphorylation of p47 are important for Golgi disassembly-assembly during the cell cycle
    Keiji Uchiyama
    Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY, UK
    J Cell Biol 161:1067-79. 2003
    ....
  99. pmc Role for non-proteolytic control of M-phase-promoting factor activity at M-phase exit
    Vincenzo D'Angiolella
    Faculty of Biotechnological Sciences and Dipartimento di Biologia e Patologia Cellulare e Molecolare L Califano, University of Napoli Federico II, Italy
    PLoS ONE 2:e247. 2007
    ..Thus, timely M-phase exit requires a tight coupling of proteolysis-dependent and proteolysis-independent mechanisms of MPF inactivation...
  100. ncbi Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo
    A Blangy
    Swiss Institute for Experimental Cancer Research, Epalinges, Switzerland
    Cell 83:1159-69. 1995
    ..These results indicate that HsEg5 is required for establishing a bipolar spindle and that p34cdc2 protein kinase directly regulates its localization...
  101. pmc Distinct activities of the related protein kinases Cdk1 and Ime2
    Kara E Sawarynski
    Barbara Ann Karmanos Cancer Institute and Department of Pathology, Wayne State University School of Medicine, 3114 Prentis Center, 110 E Warren Ave, Detroit, MI 48201, USA
    Biochim Biophys Acta 1773:450-6. 2007
    ..Examination of other substrates both in vitro and in vivo also revealed differing specificities. These results indicate that Ime2 does not simply replace G1 cyclin-CDK complexes in promoting Sic1 degradation during meiosis...

Research Grants59

  1. Role of the Y-Located TSPY Gene in Human Oncogenesis
    Yun Fai Chris Lau; Fiscal Year: 2013
    ..This project will shed important insights on how the Y-oncogene and X-tumor suppressor operate and how one can interfere or boost their actions respectively to treat prostate cancer. ..
  2. Herpesvirus protein kinases: Substrate recognition and pathway targeting.
    S Diane Hayward; Fiscal Year: 2013
    ..Selected targets will be validated and the effect of their knockdown on virus replication determined. These experiments will uncover additional cell proteins or networks that could be targets for anti-viral therapeutic strategies. ..
  3. The Role of Cks Proteins in Mammalian Meiosis
    Charles H Spruck; Fiscal Year: 2010
    ..Uncovering the function(s) of Cks2 in mammalian meiosis could lead to a better understanding about how Ml is regulated, and help to define the underlying causes of infertility and birth defects in humans. ..
  4. G2 Role For Cdk2 in Human Cells
    Gregory Enders; Fiscal Year: 2007
    ..We believe that deregulation of Cdk2, a frequent event in cancer, may contribute to genetic instability and neoplastic progression through deregulation of these functions. ..
  5. Pathways of Therapy-induced Senescence in Cancer
    Daniel Y Wu; Fiscal Year: 2010
    ..These studies should yield the clinical relevance, novel markers and new mechanistic insights of accelerated cellular senescence in human cancers. ..
  6. CONTROL OF CELL DIVISION IN FISSION YEAST
    David Beach; Fiscal Year: 1993
    The cdc2 protein kinase of fission yeast plays a critical role in regulation of the cell cycle and appears to have a homolog in all eukaryotes...
  7. CELL CYCLE CONTROL BY THE CAMP PKA SIGNAL TRANSDUCTION P
    Jean Gautier; Fiscal Year: 2002
    ..We will determine how cdc2 protein kinase increases cAMP levels and why this is blocked at the mitosis exit checkpoint...
  8. FUNCTIONS OF SRY AND SRY INTERACTIVE PROTEIN GENES
    Yun Fai Chris Lau; Fiscal Year: 2004
    ..Understanding the mechanisms of sex determination in mouse may shed insights on those in humans, and eventually may lead to developments of clinical diagnosis and treatment of gonadal dysgenesis and infertility. ..
  9. Proteolytic Control of Early Events in Mitosis
    JAMES FERRELL; Fiscal Year: 2008
    ..abstract_text> ..
  10. Effects of Ethanol on Pancreas Regeneration
    Dahn Clemens; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  11. Bistability and Biological Oscillations
    JAMES FERRELL; Fiscal Year: 2009
    ..abstract_text> ..
  12. Problem Solving Environment for Modeling the Cell Cycle
    John Tyson; Fiscal Year: 2002
    ..and some outstanding collaborators (Sible and Cross, experimental cell cycle research; Kitano and Bolouri, software development for molecular cell biology; and Kohn, bioinformatics of mammalian cell cycle controls). ..
  13. Experimental and Computational Studies of Exit from Mitosis in Budding Yeast
    John J Tyson; Fiscal Year: 2010
    ..g., embryonic development, tissue regeneration, wound healing, and carcinogenesis. ..
  14. ETHANOL OXIDATION EFFECTS ON EGF SIGNAL TRANSDUCTION
    Dahn Clemens; Fiscal Year: 2001
    ....
  15. FUNCTIONS FOR HERPES SIMPLEX VIRUS ICP22 AND US1.5
    Bernard Roizman; Fiscal Year: 2009
    ..In all instances a key question to be resolved is the contribution of each of these functions of ICP22 to the biology of the virus in the experimental animal host. ..
  16. DISSECTION OF THE FUNCTIONS OF HERPES SIMPLEX VIRUS ICPO
    Bernard Roizman; Fiscal Year: 2002
    ..The experimental design includes identification of the products of alternative splicing and characterization of the role of the ligands in infection. ..
  17. MAP Kinase and AKT Signaling in Congestive Heart Failure
    ANTHONY MUSLIN; Fiscal Year: 2009
    ..Our findings will help to identify specific signaling mechanisms involved in the regulation of cardiac myocyte growth and metabolism. ..
  18. Analysis of Suppressors of nimXcdc2 Mutations
    Sarah McGuire; Fiscal Year: 2003
    ..abstract_text> ..
  19. MyD118, CR6 and GADD45 in Genotoxic Stress
    Dan Liebermann; Fiscal Year: 2003
    ....
  20. An in vivo Screen for Radiation Sensitizers
    Tin Tin Su; Fiscal Year: 2008
    ..Successful completion of this project would establish a novel, rapid and effective primary screen in vivo for radiosensitizers with potential therapeutic value. [unreadable] [unreadable] [unreadable]..
  21. RGS PROTEIN FUNCTION IN CARDIAC PHYSIOLOGY
    ANTHONY MUSLIN; Fiscal Year: 2008
    ..These experiments will help define the role of RGS proteins in the pathogenesis of cardiac hypertrophy and contractile dysfunction and may provide important information for the development of novel therapeutic agents. ..
  22. IMMUNOTOXIC PROPERTIES OF MERCURIC COMPOUNDS
    BRUCE SHENKER; Fiscal Year: 2003
    ..The goal of this application is to better understand the pathways responsible for mercury toxicity, as well as health implications associated with exposure to mercury-containing compounds. ..
  23. NITRIC OXIDE AND RESPONSES TO HYPOXIA IN DROSOPHILA
    PATRICK O FARRELL; Fiscal Year: 2003
    ..Similar tools will be developed to dissect the signal transduction pathway that provokes adaptive changes in behavior and cell cycle progression in response to reduced oxygen. ..
  24. Phenolic component of tobacco smoke as tumor promoter
    JAGAT MUKHERJEE; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  25. DEVELOPMENTAL PROGRAMS OF CELL CYCLE CONTROL
    PATRICK O FARRELL; Fiscal Year: 2009
    ..Using real-time visualization of tagged proteins and RNAi we are detailing the interactions between cyclin:Cdk and the cytokinetic machinery. ..
  26. RNAi in DNA Sequence Elimination in Tetrahymena
    Martin A Gorovsky; Fiscal Year: 2010
    ..These studies should shed light on other RNAi- like processes that are important for normal development and maintenance of genome stability in multicellular organisms. ..
  27. Purchase of Leica TCS SP2 Confocal Microscope
    Patricia Wadsworth; Fiscal Year: 2002
    ....
  28. 14-3-3 PROTEIN FUNCTION IN CELL GROWTH AND MOTILITY
    ANTHONY MUSLIN; Fiscal Year: 2001
    ..The expectation is that the results of these experiments will establish the importance of the 14-3-3 signaling molecules in cell growth regulation and development. ..
  29. Mechanisms of Microtubule Dynamic Turnover
    Patricia Wadsworth; Fiscal Year: 2009
    ..Learning how normal cells construct a mitotic spindle is an important first step towards understanding defective cell division in cancer. ..
  30. Identification and Analysis of Flavivirus Protease and RNA Helicase Inhibitors
    Radhakrishnan Padmanabhan; Fiscal Year: 2009
    ....
  31. Gadd 45 in the Response of Hematopoietic Cells to Stress
    Dan A Liebermann; Fiscal Year: 2010
    ....
  32. Post-translational Modifications of High-mobility Group Proteins
    Yinsheng Wang; Fiscal Year: 2009
    ..In addition, the outcome of proposed studies may provide important molecular biomarkers for cancer diagnosis and prognosis. ..
  33. Alcohol Injury Healing, Cytoprotection and Survivin
    Michael Jones; Fiscal Year: 2009
    ..Information gained from these studies will lead to better understanding of the mechanisms underlying ETOH-induced injury and will provide for the development of better therapeutics for treating ETOH-induced injury. ..
  34. Repeated Genes: Organization, Evolution, and Function
    MARTIN GOROVSKY; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  35. REGULATION OF THE ONSET OF ANAPHASE
    Tomohiro Matsumoto; Fiscal Year: 2001
    ....
  36. Bioactive Food Comoponents, Alternative Medicine and Cancer Chemoprevention: Rece
    Shivendra Singh; Fiscal Year: 2007
    ..The theme of our symposium is highly focused and attracts leaders and highly accomplished scientists to discuss promises and challenges in cancer chemoprevention research. [unreadable] [unreadable] [unreadable] [unreadable]..
  37. Calcium Dependent Protein Kinase Autophosphorylation
    Adrian Hegeman; Fiscal Year: 2004
    ..The autophosphorylation sites will be altered by site directed mutagenesis, and the effects of these changes will be evaluated in vitro and in vivo. ..
  38. Cell Cycle G2/M Pathway Modulated by Viral Protein R
    Richard Zhao; Fiscal Year: 2006
    ..These proposed studies will provide a comprehensive framework for this new cell cycle control pathway and provide insights into fundamental aspects of this new G2/M surveillance system of eukaryotic cells. ..
  39. Early Stage Training in the Neurosciences
    Peter Hitchcock; Fiscal Year: 2005
    ..During the second year students take elective neuroscience courses, participate in an intensive neuroscience seminar course, complete their lab rotations and begin the initial work on the doctoral thesis. ..
  40. CONTROL OF GENE ACTIVITY AND ORGANELLE BIOGENESIS
    MARTIN GOROVSKY; Fiscal Year: 2006
    ..abstract_text> ..
  41. Immunosuppressive Proteins Produced by Oral Pathogens
    BRUCE SHENKER; Fiscal Year: 2006
    ....
  42. Cell Cycle Regulation by Checkpoints in Drosophila
    Tin Tin Su; Fiscal Year: 2006
    ..Aim 4) We will screen through existing mutagensensitive Drosophila mutants for their ability to regulate mitosis, S phase and cell death after irradiation, in order to uncover novel genes needed for proper response to DNA damage. ..
  43. TLS and TLS Fusion Proteins in Leukemia
    Liu Yang; Fiscal Year: 2005
    ..It is envisioned that successful completion of this project will unveil potential therapeutic targets in the treatment of human leukemias characterized by the t(16;21) translocation. ..
  44. Metabolism of Carcinogens and Drugs by Human P450s
    F Guengerich; Fiscal Year: 2005
    ..Successful completion of these collective studies should provide better understanding of the ways in which human P450s catalyze oxidation of carcinogens and drugs and the significance of variations in these enzymes. ..
  45. Mechanism of Meclp in the Checkpoint Response
    GEORGE BRUSH; Fiscal Year: 2006
    ..It is expected that these studies will provide significant insight into the molecular mechanisms underlying maintenance of the non-cancerous state under genotoxic conditions. ..
  46. Vasculature is a determinant of epithelial morphogenesis
    MARGARET SCHWARZ; Fiscal Year: 2006
    ..Thus, identifying the factors responsible for coordinating vascular formation and distal lung morphogenesis will provide insight into the determinants by which their balance can affect lung development. ..
  47. MECHANISMS OF NUCLEAR ENVELOPE BREAKDOWN
    Mark Terasaki; Fiscal Year: 2004
    ..These studies should provide information about the fundamental question of the regulation of the cell cycle. ..
  48. Chk1 signaling in the G2 DNA damage checkpoint
    MATTHEW O CONNELL; Fiscal Year: 2007
    ..The study will yield data that will be important in terms of both the basic biology of the cell cycle and stability of the genome and also in the testing of new approaches and new targets for cancer therapy. [unreadable] [unreadable]..
  49. MyD118/CR6/GADD45 in Hematopoietic Homeostasis
    Dan Liebermann; Fiscal Year: 2005
    ....
  50. NITRIC OXIDE AND RESPONSES TO HYPOXIA IN DROSOPHILA
    PATRICK O FARRELL; Fiscal Year: 2007
    ..These studies will provide new models for the action of signals central to human physiology and health. [unreadable] [unreadable] [unreadable]..
  51. EMAP II Regulation of Pulmonary Cell Proliferation
    MARGARET SCHWARZ; Fiscal Year: 2007
    ..abstract_text> ..
  52. FUNCTIONAL ANALYSIS OF DENGUE VIRUS ANTIGENS NS3 AND NS5
    Radhakrishnan Padmanabhan; Fiscal Year: 2003
    ..4. NS3/NS5 interaction is regulated by phosphorylation and subcellular location of NS5. The PI proposes to test the hypothesis that the nuclear NS5 regulates the expression of cellular gene(s) in response to viral infection. ..
  53. Cell Growth and Radiation Survival in Drosophila
    Tin Tin Su; Fiscal Year: 2007
    ..Understanding radiation survival in a multicellular context could help identify potential therapies for when we do not want cells to survive irradiation, such as in the treatment of cancer. ..
  54. CHONDROGENESIS AND HISTONE MODIFICATION ENZYMES
    Liu Yang; Fiscal Year: 2007
    ....
  55. T lymphocyte growth regulation by prointerleukin-16
    Kevin Wilson; Fiscal Year: 2005
    ..Such an environment maximizes the potential for the principle investigator to establish a scientific niche from which an academic career can be constructed. ..
  56. Dengue and West Nile Viral Protease Inhibitors
    Radhakrishnan Padmanabhan; Fiscal Year: 2005
    ..Since there is no effective vaccine available for either DEN or WNV, this antiviral strategy is likely to yield lead inhibitors useful as therapeutic agents in the control of these lethal pathogens. ..
  57. ROS-induced Nucleic Acid Damage
    Yinsheng Wang; Fiscal Year: 2006
    ..The outcome of the research proposed here will provide better understanding of the biological consequences of oxidative damage on nucleic acids by ROS and their implications in human health. ..
  58. MOLECULAR MECHANISMS OF RETINA-SPECIFIC GENE EXPRESSION
    Peter Hitchcock; Fiscal Year: 2008
    ..A better understanding of transcriptional regulatory pathways may allow us to experimentally manipulate the expression of specific target gene(s) to correct a disease phenotype. [unreadable] [unreadable] [unreadable]..
  59. Effect of HIV-1 Vpr on Basic Cellular Functions (II)
    Richard Zhao; Fiscal Year: 2007
    ..abstract_text> ..