cyclin dependent kinases

Summary

Summary: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.

Top Publications

  1. ncbi Cancer cell cycles
    C J Sherr
    Howard Hughes Medical Institute, Department of Tumor Cell Biology, St Jude Children s Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA
    Science 274:1672-7. 1996
  2. ncbi A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4
    M Serrano
    Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724
    Nature 366:704-7. 1993
  3. ncbi SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27
    A C Carrano
    Department of Pathology, New York University Medical Center, New York 10016, USA
    Nat Cell Biol 1:193-9. 1999
  4. 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
  5. ncbi p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21
    H Toyoshima
    Molecular Biology and Virology Laboratory, Salk Institute, La Jolla, California 92037
    Cell 78:67-74. 1994
  6. ncbi To cycle or not to cycle: a critical decision in cancer
    M Malumbres
    Molecular Oncology Program, Centro Nacional de Investigaciones Oncologicas, Madrid, Spain
    Nat Rev Cancer 1:222-31. 2001
  7. ncbi Cyclin E-CDK2 is a regulator of p27Kip1
    R J Sheaff
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center FHCRC, Seattle, Washington 98104, USA
    Genes Dev 11:1464-78. 1997
  8. ncbi Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex
    P D Jeffrey
    Cellular Biochemistry and Biophysics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Nature 376:313-20. 1995
  9. ncbi New functional activities for the p21 family of CDK inhibitors
    J LaBaer
    Massachusetts General Hospital Cancer Center, Charlestown 02129, USA
    Genes Dev 11:847-62. 1997
  10. ncbi CDK activity antagonizes Whi5, an inhibitor of G1/S transcription in yeast
    Michael Costanzo
    Department of Medical Genetics and Microbiology, University of Toronto, 1 King s College Circle, Toronto, M5S 1A8, Canada
    Cell 117:899-913. 2004

Detail Information

Publications385 found, 100 shown here

  1. ncbi Cancer cell cycles
    C J Sherr
    Howard Hughes Medical Institute, Department of Tumor Cell Biology, St Jude Children s Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA
    Science 274:1672-7. 1996
    ..Like the tumor suppressor protein p53, components of this "RB pathway," although not essential for the cell cycle per se, may participate in checkpoint functions that regulate homeostatic tissue renewal throughout life...
  2. ncbi A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4
    M Serrano
    Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724
    Nature 366:704-7. 1993
    ..p16 seems to act in a regulatory feedback circuit with CDK4, D-type cyclins and retinoblastoma protein...
  3. ncbi SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27
    A C Carrano
    Department of Pathology, New York University Medical Center, New York 10016, USA
    Nat Cell Biol 1:193-9. 1999
    ..Thus, p27 degradation is subject to dual control by the accumulation of both SKP2 and cyclins following mitogenic stimulation...
  4. 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...
  5. ncbi p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21
    H Toyoshima
    Molecular Biology and Virology Laboratory, Salk Institute, La Jolla, California 92037
    Cell 78:67-74. 1994
    ..p27 is identical to p27Kip1, a cyclin-Cdk inhibitor present in TGF beta-treated cells. p27 has the hallmarks of a negative regulator of G1 progression and may mediate TGF beta-induced G1 arrest...
  6. ncbi To cycle or not to cycle: a critical decision in cancer
    M Malumbres
    Molecular Oncology Program, Centro Nacional de Investigaciones Oncologicas, Madrid, Spain
    Nat Rev Cancer 1:222-31. 2001
    ..Understanding the molecular mechanisms that underlie this commitment should provide important insights into how normal cells become tumorigenic and how new anticancer strategies can be devised...
  7. ncbi Cyclin E-CDK2 is a regulator of p27Kip1
    R J Sheaff
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center FHCRC, Seattle, Washington 98104, USA
    Genes Dev 11:1464-78. 1997
    ....
  8. ncbi Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex
    P D Jeffrey
    Cellular Biochemistry and Biophysics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Nature 376:313-20. 1995
    ..These changes activate the kinase by realigning active site residues and relieving the steric blockade at the entrance of the catalytic cleft...
  9. ncbi New functional activities for the p21 family of CDK inhibitors
    J LaBaer
    Massachusetts General Hospital Cancer Center, Charlestown 02129, USA
    Genes Dev 11:847-62. 1997
    ..We suggest that in addition to their roles as inhibitors, the p21 family of proteins, originally identified as inhibitors, may also have roles as adaptor proteins that assemble and program kinase complexes for specific functions...
  10. ncbi CDK activity antagonizes Whi5, an inhibitor of G1/S transcription in yeast
    Michael Costanzo
    Department of Medical Genetics and Microbiology, University of Toronto, 1 King s College Circle, Toronto, M5S 1A8, Canada
    Cell 117:899-913. 2004
    ..Elimination of CDK activity at the end of mitosis allows Whi5 to reenter the nucleus to again repress G1/S transcription. These findings harmonize G1/S control in eukaryotes...
  11. ncbi A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA
    P Wei
    Regulatory Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037 1099, USA
    Cell 92:451-62. 1998
    ..Moreover, overexpression of human cyclin T rescues Tat activity in nonpermissive rodent cells. We propose that Tat directs cyclin T-CDK9 to RNAPII through cooperative binding to TAR RNA...
  12. ncbi The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases
    J W Harper
    Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030
    Cell 75:805-16. 1993
    ..Cotransfection experiments indicate that CIP1 and SV40 T antigen function in a mutually antagonistic manner to control cell cycle progression...
  13. ncbi The Pezcoller lecture: cancer cell cycles revisited
    C J Sherr
    Howard Hughes Medical Institute and Department of Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Cancer Res 60:3689-95. 2000
    ..Lesions in the p16--cyclin D-CDK4--Rb and ARF--Mdm2--p53 pathways occur so frequently in cancer, regardless of patient age or tumor type, that they appear to be part of the life history of most, if not all, cancer cells...
  14. ncbi Mammalian cyclin-dependent kinases
    Marcos Malumbres
    Molecular Oncology Programme, Centro Nacional de Investigaciones Oncologicas, Melchor Fernandez Almagro 3, E 28029 Madrid, Spain
    Trends Biochem Sci 30:630-41. 2005
    ..These findings have important implications both for our current understanding of the role of Cdks in regulating the mammalian cell cycle and for their potential use as therapeutic targets in cancer...
  15. ncbi How proteolysis drives the cell cycle
    R W King
    Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA
    Science 274:1652-9. 1996
    ..Proteolysis therefore drives cell cycle progression not only by regulating CDK activity, but by directly influencing chromosome and spindle dynamics...
  16. ncbi Dissecting the regulatory circuitry of a eukaryotic genome
    F C Holstege
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    Cell 95:717-28. 1998
    ....
  17. ncbi Cell cycle, CDKs and cancer: a changing paradigm
    Marcos Malumbres
    Cell Division and Cancer Group, Molecular Oncology Programme, Centro Nacional de Investigaciones Oncologicas CNIO, 28029 Madrid, Spain
    Nat Rev Cancer 9:153-66. 2009
    ..Emerging evidence suggests that tumour cells may also require specific interphase CDKs for proliferation. Thus, selective CDK inhibition may provide therapeutic benefit against certain human neoplasias...
  18. 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...
  19. ncbi Translational control of p27Kip1 accumulation during the cell cycle
    L Hengst
    Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037, USA
    Science 271:1861-4. 1996
    ....
  20. pmc Negative regulation of Gcn4 and Msn2 transcription factors by Srb10 cyclin-dependent kinase
    Y Chi
    Division of Biology, California Institute of Technology, Pasadena 91125, USA
    Genes Dev 15:1078-92. 2001
    ..Simultaneous down-regulation of both transcriptional regulatory proteins and RNA polymerase may enhance the potency and specificity of transcriptional inhibition by Srb10...
  21. ncbi ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks
    Ali Jazayeri
    The Wellcome Trust and Cancer Research UK Gurdon Institute, and Department of Zoology, Cambridge University, Tennis Court Road, Cambridge, CB2 1QN, UK
    Nat Cell Biol 8:37-45. 2006
    ..Thus, in response to DSBs, ATR activation is regulated by ATM in a cell-cycle dependent manner...
  22. ncbi Temporal regulation of RNA polymerase II by Srb10 and Kin28 cyclin-dependent kinases
    C J Hengartner
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    Mol Cell 2:43-53. 1998
    ....
  23. ncbi Mediator expression profiling epistasis reveals a signal transduction pathway with antagonistic submodules and highly specific downstream targets
    Jeroen van de Peppel
    Department of Physiological Chemistry, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Mol Cell 19:511-22. 2005
    ..Expression profiling can therefore precisely map regulatory cascades, and our findings support a role for Mediator as a direct processor of signaling pathways for determining specificity...
  24. ncbi Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle
    A Koff
    Department of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98104
    Science 257:1689-94. 1992
    ..These results provide further evidence that in all eukaryotes assembly of a cyclin-Cdk complex is an important step in the biochemical pathway that controls cell proliferation during G1...
  25. ncbi Serine 732 phosphorylation of FAK by Cdk5 is important for microtubule organization, nuclear movement, and neuronal migration
    Zhigang Xie
    Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Cell 114:469-82. 2003
    ..Taken together, these results suggest that Cdk5 phosphorylation of FAK is critical for neuronal migration through regulation of a microtubule fork important for nuclear translocation...
  26. ncbi Phosphorylation of Sld2 and Sld3 by cyclin-dependent kinases promotes DNA replication in budding yeast
    Philip Zegerman
    Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
    Nature 445:281-5. 2007
    ..DNA replication in cells lacking G1 phase CDK (G1-CDK) required expression of the Cdc7 kinase regulatory subunit, Dbf4, as well as Sld2 and Sld3 bypass. Our results help to explain how G1- and S-CDKs promote DNA replication in yeast...
  27. ncbi CDK-dependent phosphorylation of Sld2 and Sld3 initiates DNA replication in budding yeast
    Seiji Tanaka
    Division of Microbial Genetics, National Institute of Genetics, Research Organization of Information and Systems, SOKENDAI, Yata 1111, Mishima, Shizuoka 411 8540, Japan
    Nature 445:328-32. 2007
    ....
  28. ncbi Mice lacking p27(Kip1) display increased body size, multiple organ hyperplasia, retinal dysplasia, and pituitary tumors
    K Nakayama
    Department of Biology, Nippon Roche Research Center, Kamakura, Kanagawa, Japan
    Cell 85:707-20. 1996
    ..Unexpectedly, the cell cycle arrest mediated by TGFbeta, rapamycin, or contact inhibition remained intact in p27(-/-) cells, suggesting that p27(Kip1) is not required in these pathways...
  29. pmc Genome-wide analysis of core cell cycle genes in Arabidopsis
    Klaas Vandepoele
    Department of Plant Systems Biology, Flanders Interuniversity Institute for Biotechnology VIB, Ghent University, K L Ledeganckstraat 35, B 9000 Ghent, Belgium
    Plant Cell 14:903-16. 2002
    ..This genome-wide analysis illustrates the complexity of the plant cell cycle machinery and provides a tool for elucidating the function of new family members in the future...
  30. ncbi Cyclin-dependent kinases: engines, clocks, and microprocessors
    D O Morgan
    Department of Physiology, University of California, San Francisco 94143 0444, USA
    Annu Rev Cell Dev Biol 13:261-91. 1997
    ..In the cell, these regulatory mechanisms generate an interlinked series of Cdk oscillators that trigger the events of cell division...
  31. pmc Dynamic association of capping enzymes with transcribing RNA polymerase II
    S C Schroeder
    Department of Biochemistry and Molecular Genetics, UCHSC, Denver, Colorado 80262, USA
    Genes Dev 14:2435-40. 2000
    ..CTD phosphorylation and dephosphorylation therefore control the association of capping enzymes with pol II as it transcribes a gene...
  32. pmc Nim1-related kinases coordinate cell cycle progression with the organization of the peripheral cytoskeleton in yeast
    Y Barral
    Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520 8103 USA
    Genes Dev 13:176-87. 1999
    ..Moreover, Hsl1, Kcc4, and Gin4 have homologs in higher eukaryotes, suggesting that the regulation of Swe1/Wee1 by this class of kinases is highly conserved...
  33. ncbi p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest
    G J Hannon
    Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724
    Nature 371:257-61. 1994
    ..The gene encoding p15 is located on chromosome 9 adjacent to the p16 gene at a frequent site of chromosomal abnormality in human tumours (9p21)...
  34. ncbi ERK induces p35, a neuron-specific activator of Cdk5, through induction of Egr1
    T Harada
    Department of Biophysics, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
    Nat Cell Biol 3:453-9. 2001
    ..Our results thus define an essential signalling pathway, downstream of ERK/MAPK, that leads to neuronal differentiation...
  35. pmc p21 is a critical CDK2 regulator essential for proliferation control in Rb-deficient cells
    J Brugarolas
    Department of Biology, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Cell Biol 141:503-14. 1998
    ..Finally, animals with the genotype Rb+/-;p21(-/-) succumbed to tumors more rapidly than Rb+/- mice, suggesting that in certain contexts mutations in these two cell cycle regulators can cooperate in tumor development...
  36. ncbi Deregulated degradation of the cdk inhibitor p27 and malignant transformation
    Joanna Bloom
    Department of Pathology and NYU Cancer Instutute, MSB599, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
    Semin Cancer Biol 13:41-7. 2003
    ..More recent evidence suggests that Skp2, the specific recognition factor for p27 ubiquitination, has oncogenic properties. This review will focus on the regulation of p27 proteolysis and its consequences for tumorigenesis...
  37. ncbi Phosphorylation of the transcription factor PHO4 by a cyclin-CDK complex, PHO80-PHO85
    A Kaffman
    School of Medicine, Department of Biochemistry and Biophysics, University of California at San Francisco 94143
    Science 263:1153-6. 1994
    ..These results demonstrate the existence of a cyclin-cdk complex that is used for a regulatory process other than cell-cycle control and identify a physiologically relevant substrate for this complex...
  38. ncbi Multiple levels of cyclin specificity in cell-cycle control
    Joanna Bloom
    Laboratory of Yeast Molecular Genetics, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nat Rev Mol Cell Biol 8:149-60. 2007
    ....
  39. ncbi Cyclin-dependent kinase inhibitors sensitize tumor cells to nutlin-induced apoptosis: a potent drug combination
    Chit Fang Cheok
    Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673
    Mol Cancer Res 5:1133-45. 2007
    ....
  40. ncbi Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex
    A A Russo
    Cellular Biochemistry and Biophysics Program, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York 10021, USA
    Nature 382:325-31. 1996
    ..On cyclin A, it binds in a groove formed by conserved cyclin box residues. On Cdk2, it binds and rearranges the amino-terminal lobe and also inserts into the catalytic cleft, mimicking ATP...
  41. pmc Site-specific Srb10-dependent phosphorylation of the yeast Mediator subunit Med2 regulates gene expression from the 2-microm plasmid
    Magnus Hallberg
    Department of Medical Biochemistry and Biophysics, Umea University, SE 901 87 Umea, Sweden
    Proc Natl Acad Sci U S A 101:3370-5. 2004
    ..Combined with previous studies on the effects of SRB10/SRB11 deletions, our data suggest that posttranslational modifications of Mediator subunits are important for regulation of gene expression...
  42. pmc DNA topoisomerase I inhibition by camptothecin induces escape of RNA polymerase II from promoter-proximal pause site, antisense transcription and histone acetylation at the human HIF-1alpha gene locus
    Laura Baranello
    G Moruzzi Department of Biochemistry, University of Bologna, Bologna, Italy
    Nucleic Acids Res 38:159-71. 2010
    ..A changed balance of antisense transcripts and mRNAs may then lead to altered regulation of HIF-1alpha activity in human cancer cells...
  43. pmc Cyclin-binding motifs are essential for the function of p21CIP1
    J Chen
    Department of Pathology, Division of Molecular Oncology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 16:4673-82. 1996
    ..The Cy sequences may be general motifs used by Cdk inhibitors or substrates to interact with the cyclin in a cyclin-Cdk complex...
  44. ncbi p19Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S phase kinase
    H Zhang
    Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724, USA
    Cell 82:915-25. 1995
    ..The abundance of p45 is greatly increased in many transformed cells. This could result in changes in cell cycle control that contribute to the process of cellular transformation...
  45. ncbi 14-3-3epsilon is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome
    Kazuhito Toyo-oka
    Department of Pediatrics, UCSD Cancer Center, University of California, San Diego School of Medicine, 9500 Gilman Drive, Mailstop 0627, La Jolla, California 92093 0627, USA
    Nat Genet 34:274-85. 2003
    ..3 deletions...
  46. pmc Requirement of B2-type cyclin-dependent kinases for meristem integrity in Arabidopsis thaliana
    Stig Uggerhøj Andersen
    Max Planck Institute for Developmental Biology, AG Lohman, D 72076, Tubingen, Germany
    Plant Cell 20:88-100. 2008
    ..In addition, strong alterations in hormone signaling both at the level of active hormones and with respect to transcriptional and physiological outputs were observed in plants with disturbed CDKB2 activity...
  47. ncbi Structural basis for the synthesis of indirubins as potent and selective inhibitors of glycogen synthase kinase-3 and cyclin-dependent kinases
    Panagiotis Polychronopoulos
    Laboratory of Pharmacognosy and Laboratory of Pharmaceutical Chemistry, Department of Pharmacy, University of Athens, Panepistimiopolis Zografou, GR 15771 Athens, Greece
    J Med Chem 47:935-46. 2004
    ..Predicted molecules, including 6-substituted and 5,6-disubstituted indirubins, were synthesized and evaluated as CDK and GSK-3 inhibitors. Control, kinase-inactive indirubins were obtained by introduction of a methyl substitution on N1...
  48. ncbi In vitro and in vivo pharmacokinetic-pharmacodynamic relationships for the trisubstituted aminopurine cyclin-dependent kinase inhibitors olomoucine, bohemine and CYC202
    Florence I Raynaud
    Cancer Research UK Centre for Cancer Therapeutics at The Institute of Cancer Research, Haddow Laboratories, Belmont, Sutton, United Kingdom
    Clin Cancer Res 11:4875-87. 2005
    ..To investigate pharmacokinetic-pharmacodynamic relationships for the trisubstituted aminopurine cyclin-dependent kinase inhibitors olomoucine, bohemine, and CYC202 (R-roscovitine; seliciclib) in the HCT116 human colon carcinoma model...
  49. pmc The cyclin-dependent kinase inhibitor KRP2 controls the onset of the endoreduplication cycle during Arabidopsis leaf development through inhibition of mitotic CDKA;1 kinase complexes
    Aurine Verkest
    Department of Plant Systems Biology, Flanders Interuniversity Institute for Biotechnology, Ghent University, B 9052 Gent, Belgium
    Plant Cell 17:1723-36. 2005
    ..Moreover, the proposed model allowed a dynamical simulation of the in vivo observations, validating the sufficiency of the regulatory interactions between CDKA;1, KRP2, and CDKB1;1 in fine-tuning the mitosis-to-endocycle transition...
  50. ncbi Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5
    J A Bibb
    Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nature 410:376-80. 2001
    ..Our results suggest that changes in Cdk5 levels mediated by DeltaFosB, and resulting alterations in signalling involving D1 dopamine receptors, contribute to adaptive changes in the brain related to cocaine addiction...
  51. ncbi GAL4 is regulated by the RNA polymerase II holoenzyme-associated cyclin-dependent protein kinase SRB10/CDK8
    M Hirst
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada
    Mol Cell 3:673-8. 1999
    ..These results demonstrate a function for the SRB10/ CDK8 holoenzyme-associated CDK that involves regulation of transactivators by phosphorylation during transcriptional activation...
  52. pmc p27kip1: a multifunctional cyclin-dependent kinase inhibitor with prognostic significance in human cancers
    R V Lloyd
    Department of Laboratory Medicine and Pathology, Mayo Foundation and Mayo Clinic, Rochester, Minnesota 55905, USA
    Am J Pathol 154:313-23. 1999
    ..We also review studies indicating the increasingly important roles of p27, other CDKIs, and cyclins in endocrine cell hyperplasia and tumor development...
  53. ncbi Hormone-induced proliferation and differentiation of granulosa cells: a coordinated balance of the cell cycle regulators cyclin D2 and p27Kip1
    R L Robker
    Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Endocrinol 12:924-40. 1998
    ....
  54. pmc Two cyclin-dependent kinases promote RNA polymerase II transcription and formation of the scaffold complex
    Ying Liu
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center and Howard Hughes Medical Institute, Seattle, Washington 98109, USA
    Mol Cell Biol 24:1721-35. 2004
    ..In addition to the previously known substrate, the Pol II CTD, it was found that Kin28 phosphorylates two subunits of Mediator and Srb10 targets two subunits of TFIID for phosphorylation...
  55. ncbi Induction of p21 by p53 following DNA damage inhibits both Cdk4 and Cdk2 activities
    Guangan He
    Department of Experimental Therapeutics, The University of Texas, MD Anderson Cancer Center, Box 019, 1515 Holcombe Blvd, Houston, TX 77030, USA
    Oncogene 24:2929-43. 2005
    ....
  56. ncbi C/EBPalpha arrests cell proliferation through direct inhibition of Cdk2 and Cdk4
    H Wang
    Department of Pathology and Huffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Mol Cell 8:817-28. 2001
    ..Our data demonstrate that the liver-specific transcription factor C/EBPalpha brings about growth arrest through direct inhibition of cdk2 and cdk4...
  57. ncbi Mammalian cells cycle without the D-type cyclin-dependent kinases Cdk4 and Cdk6
    Marcos Malumbres
    Molecular Oncology Program, Centro Nacional de Investigaciones Oncologicas CNIO, E 28029 Madrid, Spain
    Cell 118:493-504. 2004
    ..These results indicate that D-type cyclin-dependent kinases are not essential for cell cycle entry and suggest the existence of alternative mechanisms to initiate cell proliferation upon mitogenic stimulation...
  58. pmc Regulation of G0 entry by the Pho80-Pho85 cyclin-CDK complex
    Valeria Wanke
    Department of Microbiology and Molecular Medicine, CMU, University of Geneva, Geneva, Switzerland
    EMBO J 24:4271-8. 2005
    ..Importantly, we also show that Pho80-Pho85 and TORC1 converge on a single amino acid in Rim15. Thus, Rim15 plays a key role in G0 entry through its ability to integrate signaling from the PKA, TORC1, and Pho80-Pho85 pathways...
  59. ncbi CDK-related protein kinases in plants
    J Joubès
    Laboratory of Plant Physiology, National Institute for Agronomic Research INRA, Villenave D Ornon, France
    Plant Mol Biol 43:607-20. 2000
    ..The CDKD class includes the plant orthologues of metazoan CDK7, which correspond to the CDK-activating kinase (CAK). At present, no functional information is available in plants for CDKC and CDKE...
  60. ncbi TFIIH is negatively regulated by cdk8-containing mediator complexes
    S Akoulitchev
    Howard Hughes Medical Institute, Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    Nature 407:102-6. 2000
    ..Our results link the Mediator complex and the basal transcription machinery by a regulatory pathway involving two cyclin-dependent kinases. This pathway appears to be unique to higher organisms...
  61. ncbi Preclinical and clinical development of cyclin-dependent kinase modulators
    A M Senderowicz
    DTP Clinical Trials Unit, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA
    J Natl Cancer Inst 92:376-87. 2000
    ..Thus, modulation of cdk activity is an attractive target for cancer chemotherapy, and several agents that modulate cdk activity are in or are approaching entry into clinical trials...
  62. ncbi A novel cyclin associates with MO15/CDK7 to form the CDK-activating kinase
    R P Fisher
    Department of Physiology, University of California, San Francisco 94143 0444
    Cell 78:713-24. 1994
    ..Thus, CAK is a CDK-cyclin complex implicated in the control of multiple cell cycle transitions...
  63. ncbi Regulation of cyclin-Cdk activity in mammalian cells
    A J Obaya
    Instituto Universitario de Oncologia IUOPA, Area de Fisiologia, Facultad de Medicina, Universidad de Oviedo, Spain
    Cell Mol Life Sci 59:126-42. 2002
    ..The purpose of the present review is to summarize the most important aspects of the various mechanisms implicated in cell cycle regulation...
  64. pmc Seliciclib (CYC202 or R-roscovitine), a small-molecule cyclin-dependent kinase inhibitor, mediates activity via down-regulation of Mcl-1 in multiple myeloma
    Noopur Raje
    Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Mayer 557, 44 Binney St, Boston, MA 02115, USA
    Blood 106:1042-7. 2005
    ..Finally, combination studies of seliciclib with doxorubicin and bortezomib show in vitro synergism, providing the rationale for testing these drug combinations to improve patient outcome in MM...
  65. pmc Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formation
    A Montagnoli
    Department of Pathology and Kaplan Comprehensive Cancer Center, New York University Medical Center, New York, New York 10016, USA
    Genes Dev 13:1181-9. 1999
    ..Thus throughout the cell cycle, both phosphorylation and trimeric complex formation act as signals for the ubiquitination of a Cdk inhibitor...
  66. pmc Chemical inhibition of the TFIIH-associated kinase Cdk7/Kin28 does not impair global mRNA synthesis
    Elenita I Kanin
    Department of Biochemistry and Genome Center of Wisconsin, University of Wisconsin, Madison, WI 53706, USA
    Proc Natl Acad Sci U S A 104:5812-7. 2007
    ..These results lead us to conclude that other functions of TFIIH, rather than the kinase activity, are critical for global gene transcription...
  67. pmc The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2
    M Kitagawa
    Banyu Tsukuba Research Institute in collaboration with Merck Research Laboratories, Tsukuba, Japan
    EMBO J 15:7060-9. 1996
    ..Furthermore, we found that pRB phosphorylated at Ser780 cannot bind to E2F-1 in vivo. Our data show that cyclin D1-Cdk4 and cyclin A/E Cdk2 phosphorylate different sites of pRB in vivo...
  68. ncbi Radiation-induced cell cycle arrest compromised by p21 deficiency
    J Brugarolas
    Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139, USA
    Nature 377:552-7. 1995
    ..However, p21-/- mouse embryo fibroblasts are impaired in their ability to undergo G1 arrest following DNA damage...
  69. ncbi Hyperphosphorylation of the C-terminal repeat domain of RNA polymerase II facilitates dissociation of its complex with mediator
    T Max M Søgaard
    Clare Hall Laboratories, Cancer Research UK London Research Institute, Blanche Lane, South Mimms, UK
    J Biol Chem 282:14113-20. 2007
    ..These data shed new light on mechanisms that drive the RNAPII transcription cycle and suggest a mechanism for the enhancement of CTD kinase activity by the Mediator complex...
  70. ncbi Building a cell cycle oscillator: hysteresis and bistability in the activation of Cdc2
    Joseph R Pomerening
    Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, CA 94305 5174, USA
    Nat Cell Biol 5:346-51. 2003
    ..We also show that Cdc2 activation exhibits hysteresis, a property of bistable systems with particular relevance to biochemical oscillators. These findings help establish the basic systems-level logic of the mitotic oscillator...
  71. ncbi Requirement of p27Kip1 for restriction point control of the fibroblast cell cycle
    S Coats
    Department of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA
    Science 272:877-80. 1996
    ..Therefore, p27 is an essential component of the pathway that connects mitogenic signals to the cell cycle at the restriction point...
  72. ncbi Cyclin-dependent kinases regulate the antiproliferative function of Smads
    Isao Matsuura
    Center for Advanced Biotechnology and Medicine, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA
    Nature 430:226-31. 2004
    ..Because cancer cells often contain high levels of CDK activity, diminishing Smad3 activity by CDK phosphorylation may contribute to tumorigenesis and TGF-beta resistance in cancers...
  73. ncbi Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27(Kip1)
    H Kiyokawa
    Program in Molecular Biology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Cell 85:721-32. 1996
    ..These results reflect a disturbance of the hypothalamic-pituitary-ovarian axis. The phenotypes of these mice suggest that loss of p27 causes an alteration in cell proliferation that can lead to specific endocrine dysfunction...
  74. ncbi The cdk5/p35 kinase is essential for neurite outgrowth during neuronal differentiation
    M Nikolic
    Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 10:816-25. 1996
    ..In contrast, longer neurites were elaborated in neurons that coexpressed exogenous cdk5 and p35. These observations suggest that the cdk5/p35 kinase plays a critical role in neurite outgrowth during neuronal differentiation...
  75. ncbi Srb10/Cdk8 regulates yeast filamentous growth by phosphorylating the transcription factor Ste12
    Chris Nelson
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    Nature 421:187-90. 2003
    ....
  76. pmc Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes
    A S Lundberg
    The Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    Mol Cell Biol 18:753-61. 1998
    ..Complete phosphorylation of pRb, inactivation of E2F binding, and activation of E2F transcription occur only after sequential action of at least two distinct G1 cyclin kinase complexes...
  77. ncbi PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization
    Incheol Shin
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Nat Med 8:1145-52. 2002
    ..These data indicate that Akt may contribute to tumor-cell proliferation by phosphorylation and cytosolic retention of p27, thus relieving CDK2 from p27-induced inhibition...
  78. ncbi A complex of the Srb8, -9, -10, and -11 transcriptional regulatory proteins from yeast
    Tilman Borggrefe
    Department of Structural Biology, Stanford University School of Medicine, California 94305 5400, USA
    J Biol Chem 277:44202-7. 2002
    ....
  79. ncbi Signaling phosphate starvation
    M E Lenburg
    Department of Biochemistry and Biophysics, School of Medicine, University of California at San Francisco 94143 0448, USA
    Trends Biochem Sci 21:383-7. 1996
    ..The possibility that this pathway mediates cell-cycle responses to phosphate starvation is discussed...
  80. pmc Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6
    H Hirai
    Department of Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Mol Cell Biol 15:2672-81. 1995
    ..However, introduction of a vector encoding p19 into mouse NIH 3T3 cells leads to constitutive p19 synthesis, inhibits cyclin D1-CDK4 activity in vivo, and induces G1 phase arrest...
  81. ncbi Coordinate signaling by integrins and receptor tyrosine kinases in the regulation of G1 phase cell-cycle progression
    R K Assoian
    Department of Pharmacology, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, Philadelphia, Pennsylvania 19104
    Curr Opin Genet Dev 11:48-53. 2001
    ..Recent studies have begun to reveal how this regulated signaling in the cytoplasm is linked to activation of the G1-phase cyclin-dependent kinases in the nucleus...
  82. ncbi CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repair
    Fumiko Esashi
    Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
    Nature 434:598-604. 2005
    ....
  83. ncbi The Cyclin-dependent kinase inhibitor CYC202 (R-roscovitine) inhibits retinoblastoma protein phosphorylation, causes loss of Cyclin D1, and activates the mitogen-activated protein kinase pathway
    Steven R Whittaker
    Cancer Research UK Centre for Cancer Therapeutics, Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey SM2 5NG, United Kingdom
    Cancer Res 64:262-72. 2004
    ..In addition to providing useful insights into the molecular pharmacology of CYC202 in human cancer cells, the results also suggest potential pharmacodynamic end points for use in clinical trials with the drug...
  84. ncbi Interdependent nuclear accumulation of budding yeast Cdt1 and Mcm2-7 during G1 phase
    Seiji Tanaka
    Cancer Research UK, Clare Hall Laboratories, Blanche Lane, South Mimms, EN6 3LD, UK
    Nat Cell Biol 4:198-207. 2002
    ..accumulates in the nucleus during G1 phase and is excluded from the nucleus later in the cell cycle by cyclin dependent kinases (cdks)...
  85. ncbi The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription
    Z Yang
    Department of Molecular and Cell Biology, University of California at Berkeley, USA
    Nature 414:317-22. 2001
    ..Our studies demonstrate the involvement of an snRNA in controlling the activity of a Cdk-cyclin kinase...
  86. ncbi SCF and APC: the Yin and Yang of cell cycle regulated proteolysis
    J M Peters
    Research Institute of Molecular Pathology IMP Dr Bohr Gasse 7 A 1030 Vienna Austria
    Curr Opin Cell Biol 10:759-68. 1998
    ..Both complexes are now known to exist in different forms that target different substrates for ubiquitin-dependent proteolysis...
  87. ncbi Metabolism and pharmacokinetics of the cyclin-dependent kinase inhibitor R-roscovitine in the mouse
    Bernard P Nutley
    Cancer Research UK Centre for Cancer Therapeutics, Institute of Cancer Research, Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom
    Mol Cancer Ther 4:125-39. 2005
    ..Synthetic COOH-R-roscovitine and C8-oxo-R-roscovitine were tested in functional cyclin-dependent kinase assays and shown to be less active than R-roscovitine, confirming that these metabolic reactions are deactivation pathways...
  88. ncbi Phase I trial of continuous infusion flavopiridol, a novel cyclin-dependent kinase inhibitor, in patients with refractory neoplasms
    A M Senderowicz
    Developmental Therapeutics Program Clinical Trials Unit, Medicine Branch, Biostatistics and Data Management Section, National Cancer Institute, Bethesda, MD 20892, USA
    J Clin Oncol 16:2986-99. 1998
    ....
  89. ncbi Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer
    Giuseppe Viglietto
    Istituto di Endocrinologia ed Oncologia Sperimentale, CNR c o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Naples, Italy
    Nat Med 8:1136-44. 2002
    ....
  90. ncbi Cyclin-dependent kinase pathways as targets for cancer treatment
    Geoffrey I Shapiro
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    J Clin Oncol 24:1770-83. 2006
    ..These efforts will establish whether the strategy of cdk inhibition is able to produce therapeutic benefit in the majority of human tumors...
  91. ncbi Dependence of cyclin E-CDK2 kinase activity on cell anchorage
    F Fang
    La Jolla Cancer Research Foundation, Cancer Center, CA 92037, USA
    Science 271:499-502. 1996
    ..Suppression of cyclin E-CDK2 activity may thus underlie the anchorage dependence of cell growth...
  92. ncbi Phosphorylation of the high molecular weight neurofilament protein (NF-H) by Cdk5 and p35
    D Sun
    Department of Pathology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Biol Chem 271:14245-51. 1996
    ..By immunoprecipitating Cdk5 and p35 from the transfected cells, we have been able to show that the KSPXK repeats are the preferred phosphorylation sites for Cdk5, while the KSPXY repeats are not directly phosphorylated by Cdk5 and p35...
  93. ncbi Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine phosphorylation, kinase upregulation, and neurite outgrowth
    L R Zukerberg
    Howard Hughes Medical Institute, Department of Pathology, Massachusetts General Hospital, Boston 02114, USA
    Neuron 26:633-46. 2000
    ..Furthermore, expression of active Abl resulted in lengthening of neurites. The data provide evidence for a Cables-mediated interplay between the Cdk5 and c-Abl signaling pathways in the developing nervous system...
  94. ncbi The effect of the cyclin-dependent kinase inhibitor olomoucine on cell cycle kinetics
    B Schutte
    Department of Molecular Cell Biology and Genetics, University of Maastricht, The Netherlands
    Exp Cell Res 236:4-15. 1997
    ..The presented data suggest that cyclins and CDKs are involved at an important nodal point shared by pathways regulating cellular proliferation and apoptosis...
  95. ncbi Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice
    Sagrario Ortega
    Molecular Oncology Program, Centro Nacional de Investigaciones Oncologicas, Melchor Fernandez Almagro 3, Madrid E 28029, Spain
    Nat Genet 35:25-31. 2003
    ..But CDK2 is essential for completion of prophase I during meiotic cell division in male and female germ cells, an unforeseen role for this cell cycle kinase...
  96. ncbi Complexities in the development of cyclin-dependent kinase inhibitor drugs
    Edward A Sausville
    Developmental Therapeutics Program, National Cancer Institute, Executive Plaza North Room 8018, 6130 Executive Boulevard, Rockville, MD 20852, USA
    Trends Mol Med 8:S32-7. 2002
    ..CDKs remain important and novel targets whose potential needs to be more fully explored, albeit in light of the newly emerging complexities of their cellular physiology...
  97. ncbi The cellular distribution and kinase activity of the Cdk family member Pctaire1 in the adult mouse brain and testis suggest functions in differentiation
    V Besset
    Department of Genetics, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    Cell Growth Differ 10:173-81. 1999
    ..These results suggest that Pctaire1 kinase might have an important role in differentiated cells such as postmitotic neurons and spermatogenic cells...
  98. ncbi A phase II trial of the cyclin-dependent kinase inhibitor flavopiridol in patients with previously untreated stage IV non-small cell lung cancer
    G I Shapiro
    Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Clin Cancer Res 7:1590-9. 2001
    ..A Phase II trial was conducted to determine the activity and toxicity of flavopiridol in untreated patients with metastatic NSCLC...
  99. pmc Cyclins, cyclin dependent kinases, and regulation of steroid receptor action
    N L Weigel
    Department of Molecular and Cellular Biology, 1 Baylor Plaza, Baylor College of Medicine, Houston, TX 77030, United States
    Mol Cell Endocrinol 265:157-61. 2007
    ..sites in these proteins contain Ser/Thr-Pro motifs suggesting that they are substrates for cyclin dependent kinases and/or for mitogen activated protein kinases...
  100. pmc Cyclin A- and cyclin E-Cdk complexes shuttle between the nucleus and the cytoplasm
    Mark Jackman
    Wellcome Cancer Research U K London Institute and Department of Zoology, University of Cambridge, Cambridge, United Kingdom CB2 1QR
    Mol Biol Cell 13:1030-45. 2002
    ..This has implications for the role of the hydrophobic patch as a substrate selection motif...
  101. ncbi The phosphatase Cdc14 triggers mitotic exit by reversal of Cdk-dependent phosphorylation
    R Visintin
    Whitehead Institute for Biomedical Research, Cambridge Center, Massachusetts 02142, USA
    Mol Cell 2:709-18. 1998
    ..Feedback between these pathways may lead to precipitous collapse of mitotic CDK activity and help coordinate exit from mitosis...

Research Grants66

  1. 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. ..
  2. Integrating stress MAP kinase signaling with DNA replication origin licensing
    Jeanette Gowen Cook; Fiscal Year: 2013
    ..Current paradigms rely on a combination of direct and indirect control of origin licensing by the cyclin dependent kinases (CDKs)...
  3. REGULATION OF PHOSPHOLIPID SYNTHESIS
    George M Carman; Fiscal Year: 2013
    ..The proposed work will shed light on how PAP activity is regulated, and open new avenues for understanding the control and integration of convergent and divergent lipid metabolic pathways emanating from PA. ..
  4. Organismal Radioprotection Through Pharmacological Quiescence
    JOHN S CHANT; Fiscal Year: 2010
    ..quiescence (PQ) of the early hematopoietic stem and progenitor cells (HSPC) through the inhibition of cyclin dependent kinases (CDK's) which govern the G1-S transition of the cell cycle...
  5. Cyclin-Dependent Kinase Inhibition During S Phase
    Geoffrey I Shapiro; Fiscal Year: 2013
    ..abstract_text> ..
  6. Replication licensing and cell cycle checkpoints
    Jeanette Gowen Cook; Fiscal Year: 2013
    ..The specific focus is on the coordination of this initial step with the cellular responses to perturbations in the intracellular or extracellular environment. ..
  7. The Identification and characterization of the methylation of Retinablastoma
    Louis A Saddic; Fiscal Year: 2010
    ..A better understanding of the mechanisms that control RB function in mammalian cells will ultimately provide novel ways to control RB function in age- related diseases such as cancer. ..
  8. Targeting Src Signaling Pathways to Promote Cell Cycle Arrest in Ovarian Cancer
    Fiona Simpkins; Fiscal Year: 2013
    ..Anti-estrogen treatment of early stage OVCA may prove to prevent or delay recurrence, which has never been explored. ..
  9. Walleye Dermal Sarcooma Virus Accessory Protein Function
    Sandra L Quackenbush; Fiscal Year: 2012
    ..Associations of rv-cyclin with cyclin dependent kinases 3 and 8 (cdk3 and cdk8), normally bound by host cyclin C, led to the hypothesis that rv-cyclin/cdk ..
  10. Activation of Cyclin-Dependent Kinases by Fructose-2,6-Bisphosphate
    JASON A CHESNEY; Fiscal Year: 2013
    ..Eukaryotic cell division is controlled by cyclin dependent kinases (CDKs) that bind to regulatory cyclins and phosphorylate hundreds of substrates that control DNA ..
  11. The Role of the DNA Unwinding Element Binding Protein, DUE-B, in DNA Replication
    Michael Leffak; Fiscal Year: 2010
    ..Aim 2 will characterize the effects of targeted structural mutations in DUE-B on its binding to protein ligands and its activation of replication origins. ..
  12. CIRCADIAN SYSTEM AND PRENATAL COCAINE IN ZEBRAFISH
    Irina V Zhdanova; Fiscal Year: 2013
    ....
  13. Regulation of the cell cycle by SCF and APC/C ubiquitin ligases
    Michele Pagano; Fiscal Year: 2013
    ..Given its critical role, the ubiquitin system is often deregulated in cancer cells. Thus, it is anticipated that the results of the proposed studies will have an impact on both basic science and cancer biology. ..
  14. Aging Features in Mice with Conditional Expression of p16Ink4a
    Gregory H Enders; Fiscal Year: 2013
    ..Surprisingly, none of p16's target Cyclin dependent kinases (Cdks) is essential in the mouse...
  15. Development of GZ38-1, a Novel Protectant of Chemotherapy-Induced Myelosuppressio
    JAY COPELAND STRUM; Fiscal Year: 2013
    ..a cell cycle arrest of the early hematopoietic stem and progenitor cells (HSPC) through the inhibition of cyclin dependent kinases 4 and 6 (CDK4/6) that govern the G1-S transition of the cell cycle of HSPC...
  16. Chemical Genetics of Plasmodium Kinases
    Debopam Chakrabarti; Fiscal Year: 2010
    ....
  17. NUCKS, a novel double-strand break repair gene, implicated in cancer biology
    Claudia Wiese; Fiscal Year: 2013
    ..In addition, our studies may also contribute to the improved diagnosis, prevention and treatment of cancer. ..
  18. Regulation of Hypoxia-inducible Factor 1 by Cyclin Dependent Kinases
    NOEL ANDREW WARFEL; Fiscal Year: 2013
    ..We have evidence that the stability of HIF-1? is regulated by cyclin dependent kinases (CDKs), specifically CDK1 and CDK4...
  19. Targeting the MYC Oncogene with CDK Inhibitors
    Andrei Goga; Fiscal Year: 2013
    ..The knowledge gained from these studies will facilitate the development of new therapeutics that target tumor cells with particular genetic changes by precisely inhibiting the cell division cycle. ..
  20. E-cyclins in normal and oncogenic proliferation
    Peter Sicinski; Fiscal Year: 2013
    ..To test the requirement for cyclin E function to maintain the tumorigenic potential of breast cancer cells using conditional cyclin E knockout mice;3. Analyses of novel tissue-specific cyclin E functions in vivo. ..
  21. Development of CDK4/6 Inhibitors as Novel Renal Protectants
    JAY COPELAND STRUM; Fiscal Year: 2013
    ..can be rendered transiently and reversibly quiescent by treatment with small molecule inhibitors of two cyclin dependent kinases (CDK4/6). Thus, certain cells types can be protected by PQ, without the generalized toxicity (e.g...
  22. Mechanisms of Synaptic Specificity in C. elegans
    Kang Shen; Fiscal Year: 2013
    ..Given that many neural disorders are associated with alterations in synaptic connectivity and that cyclin dependent kinases have been implicated in neurodegenerative diseases, it is hopeful that this project will help to ..
  23. Cell Cycle control by cyclin-dependent kinases
    DAVID OWEN MORGAN; Fiscal Year: 2013
    ....
  24. CELL CYCLE REGULATION IN NORMAL AND CANCER CELLS
    James M Roberts; Fiscal Year: 2010
    ..We will also test the hypothesis that misregulation of p27 in tumors causes the loss of normal coordination between cell division and cell movement, thereby contributing to the proliferative and invasive phenotype of aggressive cancers. ..
  25. Molecular Mechanisms of Prostate Cancer Chemoprevention by Apigenin
    Sanjay Gupta; Fiscal Year: 2013
    ....
  26. Role of p53 in cell cycle checkpoints
    James J Manfredi; Fiscal Year: 2013
    ..As many cancer chemotherapeutic agents exert effects by causing damage to genomic DNA, understanding the molecular basis for the involvement of p53 will identify new avenues for enhanced therapeutic efficacy. ..
  27. Cyclin-Dependent Kinases in Oncogenesis
    Peter Sicinski; Fiscal Year: 2013
    ....
  28. Mip/LIN9 and Cell Proliferation
    Oscar R Colamonici; Fiscal Year: 2012
    ..The goals proposed in this project could produce importance advancement in understanding and treatment of different types of cancer. ..
  29. Tat Transactivation
    BORIS MATIJA PETERLIN; Fiscal Year: 2013
    ..At least three additional cyclin dependent kinases play a critical role in co- transcriptional processing of HIV RNA, namely Cdk11, 12 and 13, some of which ..
  30. Regulation and function of the Clp 1p protein phosphatase
    Dannel McCollum; Fiscal Year: 2010
    Timely activation and inactivation of Cyclin dependent kinases (CDKs) regulate most cell cycle transitions...
  31. Role of Cdc25A in breast cancer
    Hiroaki Kiyokawa; Fiscal Year: 2013
    ..These studies should provide significant insight into the oncogenic roles of CDC25A, which is now regarded as a therapeutic target. ..
  32. Cyclin-dependent kinases: Novel switches in anergy and targets for tolerance
    Andrew D Wells; Fiscal Year: 2012
    ....
  33. Identifying links between the nuclear pore complex and the cell cycle
    ABIGAIL LYNN BUCHWALTER; Fiscal Year: 2013
    ..Overall, these studies will illuminate the mechanisms used to modify the number, composition, and functionality of NPCs during the cycle of cell division. ..
  34. Role of regulation of eukaryotic DNA replication in preserving genomic stability
    Joachim J Li; Fiscal Year: 2013
    ..These data will significantly enhance our understanding of how re-replication promotes genomic instability, as well as give insight into the biological significance of loss of replication control. ..
  35. Chemical Genetic Analysis of the Human Cell Cycle
    Robert P Fisher; Fiscal Year: 2013
    ..These studies promise to advance basic understanding of cell-cycle control, and to reveal novel strategies for anti-CDK therapy of human cancer. ..
  36. CKS PROTEINS IN CELL CYCLE CONTROL AND TUMOROGENESIS
    Steven I Reed; Fiscal Year: 2012
    ..In part, this is because many mechanistic questions concerning the basic biology of cancer remain unanswered. This proposal seeks to address some of these unanswered questions. ..
  37. The Role of Cell Size and G1-phase Cdks in Cell Growth Control
    Brandt L Schneider; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): G1-phase cyclin dependent kinases (Cdks) are required for proliferation and normal development...
  38. Using mouse models to understand retinoblastoma initiation and progression
    David MacPherson; Fiscal Year: 2013
    ..These secondary alterations may alter the activity of p130 through control of cyclin dependent kinases (CDKs) or may act at other points in the pathway (e.g. by regulating E2F transcription factors)...
  39. Investigation of the function and regulation of ERK3
    IRMA SANCHEZ; Fiscal Year: 2009
    MAPKs like the related cyclin dependent kinases (cdks) are a very important part of the cellular response to mitogenic stimuli, development and environmental stresses...
  40. MECHANISM, SPECIFICITY & REGULATION: CDC25 PHOSPHATASES
    Johannes Rudolph; Fiscal Year: 2004
    ..Thus, this research will greatly expand the knowledge of cell cycle transitions, their control on a molecular basis, and their role in oncogenesis. ..
  41. C/EBP alpha in Aging Liver
    Nikolai Timchenko; Fiscal Year: 2009
    ..C/EBPalpha inhibits proliferation of young livers through direct interactions with cyclin dependent kinases 2 and 4. In adipose tissues, C/EBPalpha causes growth arrest via repression of E2F transcription...
  42. Cables role in endometrial differentiation and cancer
    Bo Rueda; Fiscal Year: 2007
    ..Progesterone can influence regulatory components of the cell cycle (e.g. cyclins, cyclin dependent kinases; cdks)...
  43. STRUCTURE/FUNCTION OF CYCLIN DEPENDENT KINASES
    David Morgan; Fiscal Year: 2002
    ..The goal in this work will be to achieve a detailed biochemical understanding of the mechanisms by which this complex enzyme is assembled and regulated during mitosis. ..
  44. CELL CYCLE CONTROL IN GLOMERULAR DISEASE
    Stuart Shankland; Fiscal Year: 2007
    ..The ultimate goal is to identify new targets for potential therapies in order to reduce the heavy burden of disease in patients with gIomerular disease. ..
  45. Genetic Basis of Lung Tumor Progression in Mice
    Ming You; Fiscal Year: 2006
    ..The completion of this proposal will significantly further our understanding of tumor suppressor role of p 16(INK4a) in lung tumor progression, and of the genetic basis of lung tumor progression in mice. ..
  46. CYCLIN/CDK SUBSTRATES ESSENTIAL FOR G1 AND S PHASE
    James Roberts; Fiscal Year: 1999
    ....
  47. REGULATION OF MITOSIS BY PROTEOLYSIS IN YEAST
    Angelika Amon; Fiscal Year: 2003
    ..Identifying and characterizing the regulatory networks, such as mitotic cyclin proteolysis, that restrict the activity of these proteins will open avenues towards the development of cancer diagnostics and therapeutics. ..
  48. Immunotoxicity of indirubin, a plant-based AhR ligand
    Charles Rice; Fiscal Year: 2005
    ..The following proposal tests the hypothesis that indirubin is a potent immunotoxic compound. ..
  49. PROTEIN PHOSPHATASE 1 AND NEOPLASTIC TRNSFORMATION
    Norbert Berndt; Fiscal Year: 2004
    ..In Aim 3, the previous results will be tested by asking the question whether oncogene mediated immortalization and transformation is associated with changes affecting PP1's ability to maintain active RB. ..
  50. Characterization of the DNA replication protein Sid2p
    Elizabeth Vallen; Fiscal Year: 2002
    ..Finally, the requirement for various checkpoint and repair pathways will be analyzed to determine the molecular basis of the defect in sid2 mutant cells. ..
  51. ONCOGENE MEDIATED CHANGES IN CELL CYCLE CONTROL
    Edward Harlow; Fiscal Year: 2000
    ..These are the serum stimulated assembly of cyclin D and cdk4 complexes and the cloning and characterization of a novel cyclin D/cdk6 associated protein. ..
  52. NOVEL CYCLINS G1 AND G2
    MARY HORNE; Fiscal Year: 2002
    ..These studies will help to define processes gone awry in carcinogenesis or overproliferative immune responses, such as inflammatory and autoimmune diseases. ..
  53. MECHANISM BASED INHIBITION OF CYCLIN DEPENDENT KINASES
    Longqin Hu; Fiscal Year: 2001
    ..This approach should be generally applicable to the quick development of mechanism-based inhibitors specific for any protein serine/threonine kinase with a known specific substrate sequence. ..
  54. MECHANISMS OF NEURONAL APOPTOSIS
    HERBERT GELLER; Fiscal Year: 2000
    ....
  55. CELL CYCLE REGULATORS AS TUMOR MARKERS IN BLADDER CANCER
    Carlos Cordon Cardo; Fiscal Year: 1999
    ....
  56. P16 GENE FAMILY IN HEALTH AND DISEASE
    Gregory Hannon; Fiscal Year: 1999
    ..a new motif in cell cycle control, namely regulation of cell cycle progression by inhibitors of cyclin dependent kinases (CDKs)...
  57. Signaling Pathways in Hepatic Fibrogenesis
    Bruce Bacon; Fiscal Year: 2005
    ..Since activated HSC play a key role in hepatic fibrogenesis, these experiments will contribute to an improved understanding of the basic biochemical processes underlying hepatic fibrosis. ..
  58. SUBSTRATE TARGETING OF CYCLIN DEPENDENT KINASE
    Janet Leatherwood; Fiscal Year: 2003
    b>Cyclin Dependent Kinases (Cdks) control the many processes of cell cycle progression including DNA replication...
  59. CELL CYCLE CHECK POINTS AS TARGETS FOR NEW STRATEGIES
    Anna Janss; Fiscal Year: 2000
    ..We anticipate that these studies will provide a foundation for future pre-clinical and clinical studies of anti-tumor therapies which target G2/M cell cycle check point regulation. ..
  60. Identification of Molecular Pathways in Cancer Biology
    Michael Yaffe; Fiscal Year: 2005
    ..abstract_text> ..
  61. Cyclin-dependent Kinases and Cardiac Growth
    Michael Schneider; Fiscal Year: 2007
    ..3) To test the prediction that hypertrophic signals, through cyclin T-Cdk9, induce promoter escape by RNAPII. ..
  62. Spatially regulated functions of G1 cyclins in yeast
    Mary Miller; Fiscal Year: 2003
    ..Elucidation of the mechanisms governing cell cycle progression by Gl-cyclins in budding yeast may significantly impact our understanding of cell cycle progression in higher eukaryotic systems. ..
  63. CDK Inhibition in Cancer
    Andrei Goga; Fiscal Year: 2009
    ..The proposed training program is designed with the goal of preparing this applicant to establish an independent laboratory in an academic oncology department. ..
  64. TUMORIGENESIS AND NEUROGENESIS OF P27 KIP1 KNOCKOUT MICE
    Li Huei Tsai; Fiscal Year: 1999
    ..Using the p27-/- animal model, we will investigate the regulatory mechanisms involving both these gene products to elucidate the regulation of proliferation in this central nervous system tissue, as well. ..
  65. REGULATION OF SIC1 INHIBITION OF YEAST CDK COMPLEXES
    MICHAEL MENDENHALL; Fiscal Year: 1999
    ..Sic1 is an inhibitor of specific cyclin dependent kinases (Cdks) in yeast and a suppressor of ras transformation in animal cells...
  66. Role of Pur Alpha in Neuronal Cells
    Jennifer Gordon; Fiscal Year: 2005
    ..of Pur(alpha), which is highly expressed in neurons several key regulatory proteins including cyclins and cyclin dependent kinases coupled with its fluctuating levels throughout the cell cycle, position Pur(alpha) as a crucial factor in ..