CDK2

Summary

Gene Symbol: CDK2
Description: cyclin dependent kinase 2
Alias: CDKN2, p33(CDK2), cyclin-dependent kinase 2, cdc2-related protein kinase, cell division protein kinase 2, p33 protein kinase
Species: human

Top Publications

  1. pmc Cyclin A/CDK2 binds directly to E2F-1 and inhibits the DNA-binding activity of E2F-1/DP-1 by phosphorylation
    M Xu
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111
    Mol Cell Biol 14:8420-31. 1994
  2. ncbi Degradation of cyclin A does not require its phosphorylation by CDC2 and cyclin-dependent kinase 2
    C H Yam
    Department of Biochemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
    J Biol Chem 275:3158-67. 2000
  3. pmc Shp-1 mediates the antiproliferative activity of tissue inhibitor of metalloproteinase-2 in human microvascular endothelial cells
    Dong Wan Seo
    Cell and Cancer Biology Branch, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892 1500, USA
    J Biol Chem 281:3711-21. 2006
  4. pmc Switching Cdk2 on or off with small molecules to reveal requirements in human cell proliferation
    Karl A Merrick
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA
    Mol Cell 42:624-36. 2011
  5. doi An important role for CDK2 in G1 to S checkpoint activation and DNA damage response in human embryonic stem cells
    Irina Neganova
    Institute of Human Genetics, Newcastle University, International Centre for Life, Newcastle upon Tyne, United Kingdom
    Stem Cells 29:651-9. 2011
  6. ncbi Crystal structure of cyclin-dependent kinase 2
    H L De Bondt
    Department of Chemistry, University of California, Berkeley 94720
    Nature 363:595-602. 1993
  7. ncbi Modulation of beta-catenin phosphorylation/degradation by cyclin-dependent kinase 2
    Chun Shik Park
    Department of Life Science, Kwangju Institute of Science and Technology, 1 Oryong dong, Puk Gu, Kwangju 500 712, Korea
    J Biol Chem 279:19592-9. 2004
  8. ncbi N2-substituted O6-cyclohexylmethylguanine derivatives: potent inhibitors of cyclin-dependent kinases 1 and 2
    Ian R Hardcastle
    Northern Institute for Cancer Research, Bedson Building, School of Natural Sciences, University of Newcastle, Newcastle upon Tyne NE1 7RU, UK
    J Med Chem 47:3710-22. 2004
  9. pmc Functional flexibility of human cyclin-dependent kinase-2 and its evolutionary conservation
    Iveta Bártová
    Department of Physical Chemistry, Palacky University, 771 46 Olomouc, Czech Republic
    Protein Sci 17:22-33. 2008
  10. pmc Chemical-genetic analysis of cyclin dependent kinase 2 function reveals an important role in cellular transformation by multiple oncogenic pathways
    Dai Horiuchi
    Department of Medicine, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 109:E1019-27. 2012

Research Grants

  1. Fiona Simpkins; Fiscal Year: 2016
  2. E-cyclins in normal and oncogenic proliferation
    Peter Sicinski; Fiscal Year: 2013
  3. Geoffrey I Shapiro; Fiscal Year: 2014
  4. Peter Sicinski; Fiscal Year: 2016
  5. Mip/LIN9 and Cell Proliferation
    Oscar R Colamonici; Fiscal Year: 2012
  6. The CAK Network in Metazoan Cell Cycle Regulation
    Robert P Fisher; Fiscal Year: 2010
  7. JASON A CHESNEY; Fiscal Year: 2015
  8. Andrei Goga; Fiscal Year: 2014
  9. Chou Zen Giam; Fiscal Year: 2014
  10. Robert P Fisher; Fiscal Year: 2016

Detail Information

Publications301 found, 100 shown here

  1. pmc Cyclin A/CDK2 binds directly to E2F-1 and inhibits the DNA-binding activity of E2F-1/DP-1 by phosphorylation
    M Xu
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111
    Mol Cell Biol 14:8420-31. 1994
    ..binds to several cell cycle regulatory proteins, including the retinoblastoma family (RB, p107, p130) and cyclin A/CDK2 complexes...
  2. ncbi Degradation of cyclin A does not require its phosphorylation by CDC2 and cyclin-dependent kinase 2
    C H Yam
    Department of Biochemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
    J Biol Chem 275:3158-67. 2000
    ..and in vivo assay systems that the degradation of human cyclin A can be inhibited by kinase-inactive mutants of CDK2 and CDC2...
  3. pmc Shp-1 mediates the antiproliferative activity of tissue inhibitor of metalloproteinase-2 in human microvascular endothelial cells
    Dong Wan Seo
    Cell and Cancer Biology Branch, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892 1500, USA
    J Biol Chem 281:3711-21. 2006
    ..TIMP-2-mediated inhibition of Cdk4 and Cdk2 activity is associated with increased binding of p27Kip1 to these complexes in vivo...
  4. pmc Switching Cdk2 on or off with small molecules to reveal requirements in human cell proliferation
    Karl A Merrick
    Department of Structural and Chemical Biology, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA
    Mol Cell 42:624-36. 2011
    ..During the mammalian cell cycle, Cdk2 forms active complexes before Cdk1, but lack of Cdk2 protein does not block cell-cycle progression...
  5. doi An important role for CDK2 in G1 to S checkpoint activation and DNA damage response in human embryonic stem cells
    Irina Neganova
    Institute of Human Genetics, Newcastle University, International Centre for Life, Newcastle upon Tyne, United Kingdom
    Stem Cells 29:651-9. 2011
    ..Previously, we have shown that downregulation of cyclin-dependent kinase 2 (CDK2) in hESC causes G1 arrest, loss of pluripotency, upregulation of cell cycle inhibitors p21 and p27 and ..
  6. ncbi Crystal structure of cyclin-dependent kinase 2
    H L De Bondt
    Department of Chemistry, University of California, Berkeley 94720
    Nature 363:595-602. 1993
    Cyclin-dependent kinase 2 (CDK2) is a member of a highly conserved family of protein kinases that regulate the eukaryotic cell cycle. The crystal structures of the human CDK2 apoenzyme and its Mg2+ ATP complex have been determined to 2...
  7. ncbi Modulation of beta-catenin phosphorylation/degradation by cyclin-dependent kinase 2
    Chun Shik Park
    Department of Life Science, Kwangju Institute of Science and Technology, 1 Oryong dong, Puk Gu, Kwangju 500 712, Korea
    J Biol Chem 279:19592-9. 2004
    ..Here we demonstrate that cyclin-dependent kinase 2 (CDK2) in association with cyclin A or cyclin E directly binds to beta-catenin...
  8. ncbi N2-substituted O6-cyclohexylmethylguanine derivatives: potent inhibitors of cyclin-dependent kinases 1 and 2
    Ian R Hardcastle
    Northern Institute for Cancer Research, Bedson Building, School of Natural Sciences, University of Newcastle, Newcastle upon Tyne NE1 7RU, UK
    J Med Chem 47:3710-22. 2004
    ..5 nM and 5.4 nM vs CDK1/cyclinB and CDK2/cyclinA3, respectively)...
  9. pmc Functional flexibility of human cyclin-dependent kinase-2 and its evolutionary conservation
    Iveta Bártová
    Department of Physical Chemistry, Palacky University, 771 46 Olomouc, Czech Republic
    Protein Sci 17:22-33. 2008
    Cyclin-dependent kinase 2 (CDK2) is the most thoroughly studied of the cyclin-dependent kinases that regulate essential cellular processes, including the cell cycle, and it has become a model for studies of regulatory mechanisms at the ..
  10. pmc Chemical-genetic analysis of cyclin dependent kinase 2 function reveals an important role in cellular transformation by multiple oncogenic pathways
    Dai Horiuchi
    Department of Medicine, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 109:E1019-27. 2012
    ..Prior studies have suggested that CDK2 regulates S-phase entry and progression, and frequently shows increased activity in a wide spectrum of human tumors...
  11. pmc Phosphorylation of eukaryotic elongation factor 2 (eEF2) by cyclin A-cyclin-dependent kinase 2 regulates its inhibition by eEF2 kinase
    Asli A Hizli
    Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
    Mol Cell Biol 33:596-604. 2013
    ..We describe a new mode of eEF2 regulation and show that its phosphorylation by cyclin A-cyclin-dependent kinase 2 (CDK2) on a novel site, serine 595 (S595), directly regulates T56 phosphorylation by eEF2K...
  12. ncbi RNA interference directed to CDK2 inhibits HIV-1 transcription
    Tatyana Ammosova
    Center for Sickle Cell Disease, Howard University College of Medicine, NW, Washington, DC 20059, USA
    Virology 341:171-8. 2005
    We previously reported that cell cycle-dependent kinase 2 (CDK2) is required for human immunodeficiency virus-1 (HIV-1) Tat-dependent transcription in vitro...
  13. 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
    ..of the human p27Kip1 kinase inhibitory domain bound to the phosphorylated cyclin A-cyclin-dependent kinase 2 (Cdk2) complex has been determined at 2.3 angstrom...
  14. ncbi Abolishment of the interaction between cyclin-dependent kinase 2 and Cdk-associated protein phosphatase by a truncated KAP mutant
    Chau Ting Yeh
    Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University School of Medicine, 199, Tung Hwa North Road, Taipei 105, Taiwan
    Biochem Biophys Res Commun 305:311-4. 2003
    ..Cdk)-associated protein phosphatase (KAP) is a human dual-specificity protein phosphatase that dephosphorylates Cdk2 on a conserved threonine residue, T160, in a cyclin dependent manner...
  15. pmc Lin-28 homologue A (LIN28A) promotes cell cycle progression via regulation of cyclin-dependent kinase 2 (CDK2), cyclin D1 (CCND1), and cell division cycle 25 homolog A (CDC25A) expression in cancer
    Ning Li
    Ovarian Cancer Research Center and Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 287:17386-97. 2012
    ..Furthermore, the ability of LIN28A to stimulate translation of LIN28A-binding mRNAs, such as CDK2, was validated in vitro and in vivo...
  16. pmc LMW-E/CDK2 deregulates acinar morphogenesis, induces tumorigenesis, and associates with the activated b-Raf-ERK1/2-mTOR pathway in breast cancer patients
    Mylinh T Duong
    Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America
    PLoS Genet 8:e1002538. 2012
    Elastase-mediated cleavage of cyclin E generates low molecular weight cyclin E (LMW-E) isoforms exhibiting enhanced CDK2-associated kinase activity and resistance to inhibition by CDK inhibitors p21 and p27...
  17. ncbi Genetic selection of peptide aptamers that recognize and inhibit cyclin-dependent kinase 2
    P Colas
    Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Nature 380:548-50. 1996
    A network of interacting proteins controls the activity of cyclin-dependent kinase 2 (Cdk2) (refs 1,2) and governs the entry of higher eukaryotic cells into S phase...
  18. pmc Phosphorylation of the myristoylated protein kinase C substrate MARCKS by the cyclin E-cyclin-dependent kinase 2 complex in vitro
    S Manenti
    INSERM CJF 95 10, IFR 30, Hopital Purpan, Pavillon Rayer, 31059 Toulouse, France
    Biochem J 340:775-82. 1999
    ..We established that Cdk2, Cdk4 and, to a smaller extent, Cdk1 that have been immunoprecipitated from cellular extracts phosphorylate MARCKS...
  19. ncbi Cyclin-dependent kinase 2 regulates the interaction of Axin with beta-catenin
    Sung Il Kim
    Department of Life Science, Kwangju Institute of Science and Technology, Kwangju 500 712, Republic of Korea
    Biochem Biophys Res Commun 317:478-83. 2004
    ..amino acid sequence revealed it to contain six arginine-X-leucine (RXL) sequences, the cyclin-dependent kinase 2 (CDK2) binding motif, and 10 CDK2 consensus phosphorylation sequences...
  20. ncbi Inhibition of cyclin-dependent kinase-2 induces apoptosis in human diffuse large B-cell lymphomas
    Anthony C Faber
    Department of Biology, Boston College, Chestnut Hill, Massachusetts 02467, USA
    Cell Cycle 6:2982-9. 2007
    ..Here, we evaluated the in vitro cytotoxic activity of the cdk2 inhibitor CVT-313 against several human DLBCL cells. Treatment of DLBCL cells with CVT-313 resulted in apoptosis...
  21. ncbi Potential role of Notch1 signaling pathway in laryngeal squamous cell carcinoma cell line Hep-2 involving proliferation inhibition, cell cycle arrest, cell apoptosis, and cell migration
    Jing Jiao
    Department of Otorhinolaryngology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P R China
    Oncol Rep 22:815-23. 2009
    ..in the G0/G1 phase and induced cell apoptosis, which were coupled with the down-regulation of cyclin D1, cyclin E, cdk2 and bcl-2 and up-regulation of caspase-3, caspase-9 and p53...
  22. pmc Cyclin A2-cyclin-dependent kinase 2 cooperates with the PLK1-SCFbeta-TrCP1-EMI1-anaphase-promoting complex/cyclosome axis to promote genome reduplication in the absence of mitosis
    Hoi Tang Ma
    Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong
    Mol Cell Biol 29:6500-14. 2009
    ..In the absence of CDK1 activity, activation of APC/C and genome reduplication was dependent on cyclin A2 and CDK2. Genome reduplication was then promoted by a combination of APC/C-dependent destruction of geminin (thus releasing ..
  23. pmc Phosphorylation of MCM3 protein by cyclin E/cyclin-dependent kinase 2 (Cdk2) regulates its function in cell cycle
    Junhui Li
    Center for Molecular Immunology, Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
    J Biol Chem 286:39776-85. 2011
    ..In this study, we demonstrate that MCM3 is a substrate of cyclin E/Cdk2 and can be phosphorylated by cyclin E/Cdk2 at Thr-722...
  24. doi Human papillomavirus 18 E1^E4 protein interacts with cyclin A/CDK 2 through an RXL motif
    Qingming Ding
    Department of Pathology and Molecular Medicine, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada
    Mol Cell Biochem 373:29-40. 2013
    ..When baculovirus-produced human cyclin E and cyclin A with cdk2 were incubated in vitro with a GST-E4 fusion protein, both cyclin E and A stably interacted with the GST-E4 protein ..
  25. ncbi The fate of pancreatic tumor cell lines following p16 overexpression depends on the modulation of CDK2 activity
    J Calbo
    Department of Biochemistry and Molecular Biology, University of Barcelona, Avda Diagonal 645, Barcelona 08028, Spain
    Cell Death Differ 11:1055-65. 2004
    ..of p16 leads to G1 arrest in NP-9 cells by redistributing p21/p27 CKIs and inhibiting cyclin-dependent kinase CDK2 activity...
  26. ncbi Construction of a cyclin D1-Cdk2 fusion protein to model the biological functions of cyclin D1-Cdk2 complexes
    Anna Chytil
    Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Biol Chem 279:47688-98. 2004
    ..Cyclin D1-Cdk2 complexes were previously observed in human breast cancer cell lines, but their role in cell cycle regulation and ..
  27. pmc Phosphorylation of progesterone receptor serine 400 mediates ligand-independent transcriptional activity in response to activation of cyclin-dependent protein kinase 2
    Lisa K Pierson-Mullany
    University of Minnesota Cancer Center, MMC 806, 420 Delaware Street SE, Minneapolis, MN 55455, USA
    Mol Cell Biol 24:10542-57. 2004
    Human progesterone receptors (PR) are phosphorylated by cyclin-dependent protein kinase 2 (CDK2) at multiple sites, including Ser400. Herein, we have addressed the significance of phosphorylation of this residue...
  28. ncbi HIV-1 Tat interaction with RNA polymerase II C-terminal domain (CTD) and a dynamic association with CDK2 induce CTD phosphorylation and transcription from HIV-1 promoter
    Longwen Deng
    Department of Biochemistry and Molecular Biology, George Washington University Medical Center, Washington, D C 20037, USA
    J Biol Chem 277:33922-9. 2002
    ..We reported a Tat-associated T-cell-derived kinase, which contained CDK2. Here, we provide further evidence that CDK2 is involved in Tat-mediated CTD phosphorylation and in HIV-1 ..
  29. ncbi Cleavage of p21Cip1/Waf1 and p27Kip1 mediates apoptosis in endothelial cells through activation of Cdk2: role of a caspase cascade
    B Levkau
    Department of Pathology, University of Washington, Seattle 98195 7470, USA
    Mol Cell 1:553-63. 1998
    ..deprivation is associated with rapid and dramatic up-regulation of cyclin A-associated cyclin-dependent kinase 2(cdk2) activity...
  30. pmc Direct activation of cyclin-dependent kinase 2 by human papillomavirus E7
    Wanxia He
    Genomics ID, Kalamazoo, Michigan 49006, USA
    J Virol 77:10566-74. 2003
    Addition of human papillomavirus (HPV) E7 CDK2/cyclin A or CDK2/cyclin E, purified from either insect cells or bacteria, dramatically upregulates histone H1 kinase activity...
  31. ncbi Proteasome-mediated destruction of the cyclin a/cyclin-dependent kinase 2 complex suppresses tumor cell growth in vitro and in vivo
    Wei Chen
    Neuro Oncology Branch, National Cancer Institute, National Institutes of Neurological Disorder and Stroke, NIH, Bethesda, Maryland 20892, USA
    Cancer Res 64:3949-57. 2004
    ..we constructed a chimeric protein composed of a F-box protein (TrCP) fused to a peptide comprising the cyclin/cdk2 binding motif in p21-like cdk inhibitors (TrCP-LFG)...
  32. ncbi Cyclin-dependent kinase 2 functions in normal DNA repair and is a therapeutic target in BRCA1-deficient cancers
    Andrew J Deans
    Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
    Cancer Res 66:8219-26. 2006
    ..However, inhibition of CDKs, particularly CDK2, has not shown selective activity against most cancer cells because the kinase seems to be redundant in control of ..
  33. pmc Unscheduled Akt-triggered activation of cyclin-dependent kinase 2 as a key effector mechanism of apoptin's anticancer toxicity
    Subbareddy Maddika
    Manitoba Institute of Cell Biology, CancerCare Manitoba, University of Manitoba, Winnipeg, Manitoba R3E 0V9, Canada
    Mol Cell Biol 29:1235-48. 2009
    ..3-kinase (PI3-kinase)/Akt activation, resulting in the activation of the cyclin-dependent kinase CDK2. Inhibitors as well as dominant-negative mutants of PI3-kinase and Akt not only inhibited CDK2 activation but also ..
  34. pmc BRCA1 is phosphorylated at serine 1497 in vivo at a cyclin-dependent kinase 2 phosphorylation site
    H Ruffner
    The Salk Institute, La Jolla, California 92037, USA
    Mol Cell Biol 19:4843-54. 1999
    ..S1497 can be phosphorylated in vitro by CDK2-cyclin A or E...
  35. ncbi Specific phosphorylation of nucleophosmin on Thr(199) by cyclin-dependent kinase 2-cyclin E and its role in centrosome duplication
    Y Tokuyama
    Department of Cell Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267 0521, USA
    J Biol Chem 276:21529-37. 2001
    The kinase activity of cyclin-dependent kinase 2 (CDK2)-cyclin E is required for centrosomes to initiate duplication...
  36. ncbi How tyrosine 15 phosphorylation inhibits the activity of cyclin-dependent kinase 2-cyclin A
    Julie P I Welburn
    AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire SK10 4TF, United Kingdom
    J Biol Chem 282:3173-81. 2007
    ..Kinetic and crystallographic analyses of CDK2-cyclin A complexes reveal that this inhibitory mechanism operates through steric blockade of peptide substrate ..
  37. pmc Nuclear targeting of cyclin-dependent kinase 2 reveals essential roles of cyclin-dependent kinase 2 localization and cyclin E in vitamin D-mediated growth inhibition
    Omar Flores
    Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, 1600 NW 10th Avenue, Miami, Florida 33136, USA
    Endocrinology 151:896-908. 2010
    ..increases the stability of the cyclin-dependent kinase inhibitor p27(KIP1), decreases cyclin-dependent kinase 2 (CDK2) activity, and promotes G(1) phase accumulation in human prostate cancer cells...
  38. 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
    ..are two copies of a cyclin-binding motif in p21, Cy1 and Cy2, which interact with the cyclins independently of Cdk2. The cyclin-binding motifs of p21 are required for optimum inhibition of cyclin-Cdk kinases in vitro and for growth ..
  39. pmc Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization
    B O Petersen
    European Institute of Oncology, Department of Experimental Oncology, Via Ripamonti 435, 20141 Milan, Italy
    EMBO J 18:396-410. 1999
    ..CDC6 interacts specifically with the active Cyclin A/CDK2 complex in vitro and in vivo, but not with Cyclin E or Cyclin B kinase complexes...
  40. pmc The cyclin A1-CDK2 complex regulates DNA double-strand break repair
    Carsten Muller-Tidow
    Dept of Medicine, Hematology Oncology, University of Munster, Domagkstr 3, 48129 Munster, Germany
    Mol Cell Biol 24:8917-28. 2004
    Vertebrates express two A-type cyclins; both associate with and activate the CDK2 protein kinase. Cyclin A1 is required in the male germ line, but its molecular functions are incompletely understood...
  41. pmc Cyclin-dependent kinase 2 negatively regulates human pregnane X receptor-mediated CYP3A4 gene expression in HepG2 liver carcinoma cells
    Wenwei Lin
    Department of Chemical Biology and Therapeutics, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    J Biol Chem 283:30650-7. 2008
    ..Consistent with this finding, activation of Cdk2 attenuates the activation of CYP3A4 gene expression...
  42. pmc The cdc2-related protein p40MO15 is the catalytic subunit of a protein kinase that can activate p33cdk2 and p34cdc2
    R Y Poon
    Imperial Cancer Research Fund, Clare Hall Laboratories, Potters Bar, Herts, UK
    EMBO J 12:3123-32. 1993
    ..We conclude that p40MO15 corresponds to CAK (cdc2/cdk2 activating kinase) and speculate that, like p33cdk2 and p34cdc2, p40MO15 requires activation by phosphorylation and ..
  43. pmc Hypo-phosphorylation of the retinoblastoma protein (pRb) by cyclin D:Cdk4/6 complexes results in active pRb
    S A Ezhevsky
    Howard Hughes Medical Institute and Division of Molecular Oncology, Department of Pathology, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 94:10699-704. 1997
    ..transforming growth factor beta-mediated G1 arrest of hepatocellular carcinoma cells results in loss of Cdk2 kinase activity with continued Cdk6 kinase activity and pRb remains only hypo-phosphorylated...
  44. pmc Substrate recruitment to cyclin-dependent kinase 2 by a multipurpose docking site on cyclin A
    B A Schulman
    Massachusetts General Hospital Cancer Center, Building 149, 13th Street, Charlestown, MA 02129, USA
    Proc Natl Acad Sci U S A 95:10453-8. 1998
    ..studied the role of a conserved hydrophobic patch on the surface of cyclin A in substrate recognition by cyclin A-cdk2. This hydrophobic patch is approximately 35A away from the active site of cdk2 and contains the MRAIL sequence ..
  45. ncbi Requirement of Cdk2-cyclin E activity for repeated centrosome reproduction in Xenopus egg extracts
    E H Hinchcliffe
    Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Science 283:851-4. 1999
    ..rounds of centrosome reproduction were blocked by selective inactivation of cyclin-dependent kinase 2-cyclin E (Cdk2-E) and were restored by addition of purified Cdk2-E...
  46. ncbi Inhibitor binding to active and inactive CDK2: the crystal structure of CDK2-cyclin A/indirubin-5-sulphonate
    T G Davies
    Laboratory of Molecular Biophysics, The Rex Richards Building, University of Oxford, South Parks Road, OX1 3QU, Oxford, United Kingdom
    Structure 9:389-97. 2001
    Cyclin-dependent kinase 2 (CDK2) is an important target for structure-based design of antitumor agents. Monomeric CDK2 is inactive...
  47. ncbi The role of Thr160 phosphorylation of Cdk2 in substrate recognition
    J K Holmes
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520 8114, USA
    Eur J Biochem 268:4647-52. 2001
    ..kinases (Cdks) requires binding to a cyclin and phosphorylation on an activating site equivalent to Thr160 in Cdk2 by the Cdk-activating kinase...
  48. pmc Human Speedy: a novel cell cycle regulator that enhances proliferation through activation of Cdk2
    Lisa A Porter
    Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093 0367, USA
    J Cell Biol 157:357-66. 2002
    ..Significantly, these pathways converge to result in activation of the cyclin-dependent kinase, cdk2. It is, therefore, important to understand all the mechanisms regulating cdk2 to determine the molecular basis of ..
  49. ncbi CP110, a cell cycle-dependent CDK substrate, regulates centrosome duplication in human cells
    Zhihong Chen
    Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
    Dev Cell 3:339-50. 2002
    ..Our data suggest that CP110 is a physiological centrosomal CDK target that promotes centrosome duplication, and its deregulation may contribute to genomic instability...
  50. ncbi Structure-based design of 2-arylamino-4-cyclohexylmethyl-5-nitroso-6-aminopyrimidine inhibitors of cyclin-dependent kinases 1 and 2
    Kerry L Sayle
    Northern Institute for Cancer Research, School of Natural Sciences Chemistry, Bedson Building, University of Newcastle, Newcastle upon Tyne NE1 7RU, UK
    Bioorg Med Chem Lett 13:3079-82. 2003
    ..bearing 2-arylamino substituents was synthesised and evaluated for CDK1 and CDK2 inhibitory activity...
  51. ncbi An Rb-Skp2-p27 pathway mediates acute cell cycle inhibition by Rb and is retained in a partial-penetrance Rb mutant
    Peng Ji
    Department of Developmental and Molecular Biology, The Albert Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Mol Cell 16:47-58. 2004
    ..These results identify an Rb-Skp2-p27 pathway in Rb function, which may be involved in inhibition of tumor progression...
  52. ncbi 3',5'-cyclic nucleotide phosphodiesterase 11A: localization in human tissues
    K Loughney
    ICOS Corporation, Bothell, WA, USA
    Int J Impot Res 17:320-5. 2005
    ..No PDE11A protein was detected in blood vessels or cardiac myocytes. None of the four potential PDE11A proteins were detected in human skeletal muscle, testis, or penis...
  53. ncbi The activation and inhibition of cyclin-dependent kinase-5 by phosphorylation
    B Zhang
    Department of Chemistry, Zhejiang University, Hangzhou 310027, PR China
    Biochemistry 46:10841-51. 2007
    ..Despite the very similar 3-dimensional structures as reflected by the more than 60% identity in amino acid sequences, CDK2 and CDK5 have very different functions and characteristics...
  54. ncbi Crystal structure and mutational analysis of the human CDK2 kinase complex with cell cycle-regulatory protein CksHs1
    Y Bourne
    Department of Molecular Biology, Scripps Research Institute, La Jolla, California, 92037, USA
    Cell 84:863-74. 1996
    The 2.6 Angstrom crystal structure for human cyclin-dependent kinase 2(CDK2) in complex with CksHs1, a human homolog of essential yeast cell cycle-regulatory proteins suc1 and Cks1, reveals that CksHs1 binds via all four beta strands to ..
  55. pmc Reversal of growth suppression by p107 via direct phosphorylation by cyclin D1/cyclin-dependent kinase 4
    Xiaohong Leng
    Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Cell Biol 22:2242-54. 2002
    ..Although it is known that p107 physically associates with E- and A-type cyclin/cyclin-dependent kinase 2 (Cdk2) complexes through a cyclin-binding RXL motif located in the spacer domain, the mechanisms underlying p107 ..
  56. pmc Cyclin dependent kinase 2 and the regulation of human progesterone receptor activity
    Nicole L Moore
    Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, United States
    Steroids 72:202-9. 2007
    The function of the S phase kinase cyclin A/Cdk2 in maintaining and regulating cell cycle kinetics is well established. However an alternative role in the regulation of progesterone receptor (PR) signaling is emerging...
  57. ncbi Induction of apoptosis in uninfected lymphocytes by HIV-1 Tat protein
    C J Li
    Division of Cell Growth and Regulation, Dana Farber Cancer Institute, Boston, MA, USA
    Science 268:429-31. 1995
    ..This Tat-induced apoptosis was inhibitable by growth factors and was associated with enhanced activation of cyclin-dependent kinases...
  58. pmc Analysis of p107-associated proteins: p107 associates with a form of E2F that differs from pRB-associated E2F-1
    N Dyson
    Massachusetts General Hospital Cancer Center, Charlestown 02129
    J Virol 67:7641-7. 1993
    ..p107-associated proteins included cyclin A, cyclin E, and cdk2. In addition, p107 was found to associate with 62- to 65- and 50-kDa phosphoproteins in ML-1 cells, a human myeloid ..
  59. ncbi Interaction of cyclin-dependent kinase 2 and the Lyn tyrosine kinase in cells treated with 1-beta-D-arabinofuranosylcytosine
    Z M Yuan
    Division of Cancer Pharmacology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Oncogene 13:939-46. 1996
    The cyclin dependent kinase 2 (Cdk2) is required for initiation and progression of DNA replication. Activation of Cdk2 involves binding to cyclin E or cyclin A and dephosphorylation of Tyr15...
  60. pmc Tat protein induces self-perpetuating permissivity for productive HIV-1 infection
    C J Li
    Division of Cell Growth and Regulation, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA cjli mbcrr harvard edu
    Proc Natl Acad Sci U S A 94:8116-20. 1997
    ..Accordingly, these primary T cells progressed from G0 to the late G1 phase of the cell cycle...
  61. ncbi HIV-1 Tat elongates the G1 phase and indirectly promotes HIV-1 gene expression in cells of glial origin
    M Kundu
    Center for NeuroVirology and NeuroOncology, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania 19102, USA
    J Biol Chem 273:8130-6. 1998
    ..Consistent with this observation, lower levels of cyclin E-Cdk2 kinase activity and phosphorylated Rb were detected in the Tat-treated cells compared with the control cells...
  62. pmc Ectopic expression of Cdc25A accelerates the G(1)/S transition and leads to premature activation of cyclin E- and cyclin A-dependent kinases
    I Blomberg
    Forschungsschwerpunkt Angewandte Tumorvirologie F0400, Deutsches Krebsforschungszentrum, D 69120 Heidelberg, Germany
    Mol Cell Biol 19:6183-94. 1999
    ..Overexpression of Cdc25A in the inducible system, however, leads to a premature activation of both cyclin E-Cdk2 and cyclin A-Cdk2 complexes, while no effect of cyclin D-dependent kinases is observed...
  63. ncbi Interaction between ubiquitin-protein ligase SCFSKP2 and E2F-1 underlies the regulation of E2F-1 degradation
    A Marti
    Friedrich Miescher Institut, Basel, Switzerland
    Nat Cell Biol 1:14-9. 1999
    ....
  64. ncbi NIPP1-mediated interaction of protein phosphatase-1 with CDC5L, a regulator of pre-mRNA splicing and mitotic entry
    A Boudrez
    Afdeling Biochemie and Center for Human Genetics VIB, Faculteit Geneeskunde, Katholieke Universiteit Leuven, Belgium
    J Biol Chem 275:25411-7. 2000
    ..The binding of the FHA domain of NIPP1 to CDC5L was dependent on the phosphorylation of CDC5L, e.g. by cyclin E-Cdk2. When expressed in COS-1 or HeLa cells, the FHA domain of NIPP1 did not affect the number of cells in the G(2)/M ..
  65. ncbi p12(DOC-1), a growth suppressor, associates with DNA polymerase alpha/primase
    K Matsuo
    Laboratory of Molecular Pathology, Division of Oral Pathology, and Harvard University, School of Dental Medicine, Boston, Massachusetts 02115, USA
    FASEB J 14:1318-24. 2000
    ..mediated either by a direct inhibitory effect on pol-alpha:primase or by its effect on cyclin-dependent kinase 2 (CDK2), a recently identified p12(DOC-1)-associated protein known to stimulate DNA replication by phosphorylating pol-..
  66. ncbi TOK-1, a novel p21Cip1-binding protein that cooperatively enhances p21-dependent inhibitory activity toward CDK2 kinase
    T Ono
    Graduate School of Pharmaceutical Sciences, College of Medical Technology, Hokkaido University, Kita ku, Sapporo 060, Japan
    J Biol Chem 275:31145-54. 2000
    ..TOK-1alpha also preferentially bound to an active form of cyclin-dependent kinase 2 (CDK2) via p21, and these made a ternary complex in human cells...
  67. ncbi Proliferation of cancer cells despite CDK2 inhibition
    Osamu Tetsu
    Cancer Research Institute and Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA
    Cancer Cell 3:233-45. 2003
    We have investigated the contribution of CDK4 and CDK2 inhibition to G1 arrest in colon cancers following inhibition of the MEK/MAP kinase pathway...
  68. ncbi The tumor suppressor interferon regulatory factor 1 interferes with SP1 activation to repress the human CDK2 promoter
    Rong Lin Xie
    Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Biol Chem 278:26589-96. 2003
    ..Here we show that the G1/S phase-related cyclin-dependent kinase 2 (CDK2) gene is a novel proliferation-related downstream target of IRF1...
  69. ncbi Substrate specificity of CDK2-cyclin A. What is optimal?
    Lisa M Stevenson-Lindert
    Program in Molecular Biosciences and Engineering, University of California, Santa Barbara, California 93106, USA
    J Biol Chem 278:50956-60. 2003
    ..The catalytic efficiency of CDK2-cyclin A is impaired 2000-, 10-, and 150-fold, when Pro+1, Lys+2, or Lys+3, respectively, is substituted with Ala ..
  70. ncbi Proliferation inhibition of astrocytes, neurons, and non-glial cells by intracellularly expressed human immunodeficiency virus type 1 (HIV-1) Tat protein
    Betty Y Zhou
    Department of Microbiology adn Immunology, Indiana University School of Medicine, Indianapolis, 46202, USA
    Neurosci Lett 359:155-8. 2004
    ..showed that Tat interacted with a number of cell cycle-related proteins including cyclin A, cyclin B, cyclin D3, Cdk2, Cdk4, Cdk1/Cdc2, cdc6, p27, p53, p63, hdlg, and PCNA...
  71. pmc Phosphorylation of HIV-1 Tat by CDK2 in HIV-1 transcription
    Tatyana Ammosova
    Center for Sickle Cell Disease, Howard University College of Medicine, Washington, DC 20059, USA
    Retrovirology 3:78. 2006
    ..Earlier we showed that CDK2/cyclin E phosphorylates HIV-1 Tat in vitro...
  72. doi Knockdown of protein tyrosine phosphatase SHP-1 inhibits G1/S progression in prostate cancer cells through the regulation of components of the cell-cycle machinery
    F J Rodríguez-Ubreva
    Departamento de Bioquimica y Biologia Molecular, Universidad de Alcala, Alcala de Henares, E 28871 Madrid, Spain
    Oncogene 29:345-55. 2010
    ..The increase in p27 protein stability could also because of reduced cyclin-dependent kinase (CDK2) activity...
  73. 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
    ..The major cyclin E-associated kinase in human cells was Cdk2 (cyclin-dependent kinase 2)...
  74. ncbi Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1
    J W Harbour
    Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Cell 98:859-69. 1999
    ..This facilitates a second interaction that leads to phosphorylation of the pocket by Cdk2 and disruption of pocket structure...
  75. ncbi Cell cycle-dependent stimulation of the HIV-1 promoter by Tat-associated CAK activator
    S Nekhai
    Department of Biochemistry, George Washington University School of Medicine, Washington, DC, 20037, USA
    Virology 266:246-56. 2000
    ..The results support a mechanism whereby transactivation of the HIV promoter is regulated by cell growth signal transduction pathways that target the Tat cofactor...
  76. ncbi Induction of p53-independent p21 during ceramide-induced G1 arrest in human hepatocarcinoma cells
    W H Kim
    Department of Life Science, College of Natural Sciences, Chung Ang University, Seoul, South Korea
    Biochem Cell Biol 78:127-35. 2000
    ..In SK-Hep-1 cells, the addition of ceramide resulted in pRb dephosphorylation and G1 arrest. The activity of cdk2 was inhibited in response to ceramide during this process...
  77. ncbi Hepatitis B virus-X protein upregulates the expression of p21waf1/cip1 and prolongs G1-->S transition via a p53-independent pathway in human hepatoma cells
    U S Park
    Bioscience Research Division, Korea Research Institute of Bioscience and Biotechnology, Yusong, Taejon
    Oncogene 19:3384-94. 2000
    ..kinase inhibitor (CDKI) p21(waf1/cip1) increased binding of p21(waf1/cip1) with cyclin-dependent kinase 2 (CDK2), markedly inhibited cyclin E and CDK2 associated phosphorylation of histone H1 and induced the activation of a p21 ..
  78. ncbi Dephosphorylation of human cyclin-dependent kinases by protein phosphatase type 2C alpha and beta 2 isoforms
    A Cheng
    Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520 8114, USA
    J Biol Chem 275:34744-9. 2000
    ..reported that the activating phosphorylation on cyclin-dependent kinases in yeast (Cdc28p) and in humans (Cdk2) is removed by type 2C protein phosphatases...
  79. pmc p12(DOC-1) is a novel cyclin-dependent kinase 2-associated protein
    S Shintani
    Laboratory of Molecular Pathology, Medical School, Harvard University, Boston, Massachusetts 02115, USA
    Mol Cell Biol 20:6300-7. 2000
    ..p12(DOC-1) is a growth suppressor isolated from normal keratinocytes. We report that p12(DOC-1) associates with CDK2. More specifically, p12(DOC-1) associates with the monomeric nonphosphorylated form of CDK2 (p33CDK2)...
  80. ncbi Activation mechanism of CDK2: role of cyclin binding versus phosphorylation
    Lisa M Stevenson
    Program in Biomolecular Sciences and Engineering, University of California, Santa Barbara, California 93106, USA
    Biochemistry 41:8528-34. 2002
    ..we describe the separate roles of cyclin A binding versus phosphorylation in the overall activation mechanism of CDK2. Interaction of CDK2 with cyclin A results in a partially active complex that is moderately defective in the ..
  81. ncbi Indole-3-carbinol (I3C) inhibits cyclin-dependent kinase-2 function in human breast cancer cells by regulating the size distribution, associated cyclin E forms, and subcellular localization of the CDK2 protein complex
    Hanh H Garcia
    Department of Molecular and Cell Biology and The Cancer Research Laboratory, The University of California at Berkeley, Berkeley, California 94720, USA
    J Biol Chem 280:8756-64. 2005
    Indole-3-carbinol (I3C), a dietary compound found in cruciferous vegetables, induces a robust inhibition of CDK2 specific kinase activity as part of a G1 cell cycle arrest of human breast cancer cells...
  82. pmc The mechanism of inhibition of the cyclin-dependent kinase-2 as revealed by the molecular dynamics study on the complex CDK2 with the peptide substrate HHASPRK
    Iveta Bártová
    Department of Physical Chemistry, Palacky University, tr Svobody 26, 771 46 Olomouc, Czech Republic
    Protein Sci 14:445-51. 2005
    Molecular dynamics (MD) simulations were used to explain structural details of cyclin-dependent kinase-2 (CDK2) inhibition by phosphorylation at T14 and/or Y15 located in the glycine-rich loop (G-loop)...
  83. ncbi Cdk-inhibitory activity and stability of p27Kip1 are directly regulated by oncogenic tyrosine kinases
    Matthias Grimmler
    Max Planck Institute of Biochemistry, Am Klopferspitz 18, D 82152 Martinsried, Germany
    Cell 128:269-80. 2007
    ..Y88 phosphorylation does not prevent p27 binding to cyclin A/Cdk2. Instead, it causes phosphorylated Y88 and the entire inhibitory 3(10)-helix of p27 to be ejected from the Cdk2 ..
  84. pmc Candidate gene analysis using imputed genotypes: cell cycle single-nucleotide polymorphisms and ovarian cancer risk
    Ellen L Goode
    Department of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street Southwest, Rochester, MN 55905, USA
    Cancer Epidemiol Biomarkers Prev 18:935-44. 2009
    ..of two collaborations at a variety of SNPs in 11 cell cycle genes (CDKN2C, CDKN1A, CCND3, CCND1, CCND2, CDKN1B, CDK2, CDK4, RB1, CDKN2D, and CCNE1) and one gene region (CDKN2A-CDKN2B)...
  85. pmc Degradation of cyclin A is regulated by acetylation
    F Mateo
    Faculty of Medicine, Department of Cell Biology and Pathology, University of Barcelona, Barcelona, Spain
    Oncogene 28:2654-66. 2009
    ..All these results indicate that cyclin A acetylation at specific lysines is crucial for cyclin A stability and also has a function in the regulation of cycA-cdk activity...
  86. pmc Iron chelators of the di-2-pyridylketone thiosemicarbazone and 2-benzoylpyridine thiosemicarbazone series inhibit HIV-1 transcription: identification of novel cellular targets--iron, cyclin-dependent kinase (CDK) 2, and CDK9
    Zufan Debebe
    Center for Sickle Cell Disease, Department of Medicine, Howard University, Washington DC 20001, USA
    Mol Pharmacol 79:185-96. 2011
    ..Tat itself is phosphorylated by CDK2, and inhibition of CDK2 by small interfering RNA, the iron chelator 2-hydroxy-1-naphthylaldehyde isonicotinoyl ..
  87. doi Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry
    Xiaodong Huang
    Department of Physiological Chemistry, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    Mol Cell 42:511-23. 2011
    ..Phosphorylation of USP37 by CDK2 stimulated its full activity...
  88. pmc MicroRNA-372 is down-regulated and targets cyclin-dependent kinase 2 (CDK2) and cyclin A1 in human cervical cancer, which may contribute to tumorigenesis
    Rui Qing Tian
    Tianjin Life Science Research Center and Basic Medical School, Tianjin Medical University, Tianjin 300070, China
    J Biol Chem 286:25556-63. 2011
    ..We used bioinformatic predictions to determine that CDK2 and cyclin A1 were possible targets of miR-372 and confirmed this prediction using a fluorescent reporter assay...
  89. pmc Cyclin D1/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by site-specific phosphorylation
    L Connell-Crowley
    Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Biol Cell 8:287-301. 1997
    ..In contrast, phosphorylation of pRb by Cdk2 or Cdk3 in complexes with A- or E-type cyclins is not sufficient to inactivate pRb function in this assay, despite ..
  90. pmc Cumulative effect of phosphorylation of pRB on regulation of E2F activity
    V D Brown
    Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario M5G 1X8, Canada
    Mol Cell Biol 19:3246-56. 1999
    ..Surprisingly, no one CDK site regulated the interaction of pRB with E2F when E2F was bound to DNA. Instead, disruption of transcriptional repression resulted from accumulation of phosphate groups on the RB molecule...
  91. pmc Reciprocal activation by cyclin-dependent kinases 2 and 7 is directed by substrate specificity determinants outside the T loop
    S Garrett
    Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Mol Cell Biol 21:88-99. 2001
    ..CDK7) is the catalytic subunit of the metazoan CDK-activating kinase (CAK), which activates CDKs, such as CDC2 and CDK2, through phosphorylation of a conserved threonine residue in the T loop...
  92. ncbi Nuclear localization of the cell cycle regulator CDH1 and its regulation by phosphorylation
    Yuan Zhou
    Institute of Molecular Biology and the Department of Biochemistry, The University of Hong Kong, Hong Kong, China
    J Biol Chem 278:12530-6. 2003
    ..On the other hand, abolition of the cyclin-binding ability of CDH1 has no influence on its nuclear localization. Taken together, our findings document the phosphorylation-dependent localization of CDH1 in vertebrate cells...
  93. ncbi Phosphorylations of cyclin-dependent kinase 2 revisited using two-dimensional gel electrophoresis
    Katia Coulonval
    Institute of Interdisciplinary Research and Protein Chemistry Department, Faculte de Medecine, Universite Libre de Bruxelles, Campus Erasme, B 1070 Brussels, Belgium
    J Biol Chem 278:52052-60. 2003
    ..To re-assess the precise relationship between the different phosphorylations of CDK2, and the influence of cyclins and CDK inhibitors upon them, we introduce here the use of the high resolution power ..
  94. 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
    ....
  95. ncbi Cdk2-dependent Inhibition of p21 stability via a C-terminal cyclin-binding motif
    Hongyan Zhu
    Department of Radiation and Cellular Oncology, Center for Molecular Oncology, University of Chicago, Chicago, IL 60637, USA
    J Biol Chem 280:29282-8. 2005
    ..Recent studies have suggested that Cdk2 activity may promote p21 degradation through a pathway similar to that for p27, although the mechanism by which ..
  96. ncbi Identification of an hexapeptide that binds to a surface pocket in cyclin A and inhibits the catalytic activity of the complex cyclin-dependent kinase 2-cyclin A
    Nuria Canela
    Departament de Biologia Cellular i Anatomia Patologica, Facultat de Medicina, University of Barcelona, E 08036 Barcelona, Spain
    J Biol Chem 281:35942-53. 2006
    ..an all d-amino acid hexapeptide, termed NBI1, that inhibits the kinase activity of the cyclin-dependent kinase 2 (cdk2)-cyclin A complex through selective binding to cyclin A...
  97. pmc Effects of common germ-line genetic variation in cell cycle genes on ovarian cancer survival
    Honglin Song
    CR UK Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge CB1 8RN, United Kingdom
    Clin Cancer Res 14:1090-5. 2008
    ..Of particular interest are genes involved in cell cycle pathways, which regulate cell division and could plausibly influence clinical characteristics of multiple tumors types...
  98. pmc Distinct activation pathways confer cyclin-binding specificity on Cdk1 and Cdk2 in human cells
    Karl A Merrick
    Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Mol Cell 32:662-72. 2008
    ..these preferences in human cells and show that cyclin A assembles with Cdk1 only after complex formation with Cdk2 reaches a plateau during late S and G2 phases...
  99. pmc Phosphorylation of Ser72 is dispensable for Skp2 assembly into an active SCF ubiquitin ligase and its subcellular localization
    Tarig Bashir
    Department of Pathology, New York University Cancer Institute, Smilow Research Center, New York University School of Medicine, New York, NY, USA
    Cell Cycle 9:971-4. 2010
    ....
  100. doi CDK2 differentially controls normal cell senescence and cancer cell proliferation upon exposure to reactive oxygen species
    Chae Young Hwang
    Laboratory of Cell Signaling, Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahangno, Yusong, Daejeon 305 806, Republic of Korea
    Biochem Biophys Res Commun 425:94-9. 2012
    ..cells (including primary human dermal fibroblasts and IMR-90 cells) without affecting cyclin-dependent kinase 2 (CDK2) activity, leading to cell cycle arrest and subsequent senescence...
  101. ncbi Structural basis of cyclin-dependent kinase activation by phosphorylation
    A A Russo
    Cellular Biochemistry and Biophysics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Nat Struct Biol 3:696-700. 1996
    ..The crystal structure of the phosphorylated CDK2-CyclinA-ATP gamma S complex has been determined at 2.6 A resolution...

Research Grants64

  1. Fiona Simpkins; Fiscal Year: 2016
    ..G1 than monotherapy, with inhibition of Src, MAPK and AKT and increased p27 levels causing inhibition of cyclin E-Cdk2. While most OVCAs express ER, anti- estrogens have been disappointing...
  2. E-cyclins in normal and oncogenic proliferation
    Peter Sicinski; Fiscal Year: 2013
    ..It has been assumed that E-cyclins function as activating subunits of cyclin-dependent kinases, mostly CDK2. However, during the last funding period we demonstrated that a kinase-dead cyclin E1 mutant, which is unable to ..
  3. Geoffrey I Shapiro; Fiscal Year: 2014
    ..multiple cdk family members, the second specific aim will focus on cells in which there is combined depletion of cdk2, cdk1 and cdk9. Depletion or inhibition of this subset of cdks induces apoptosis...
  4. Peter Sicinski; Fiscal Year: 2016
    ..phase: D-type (cyclins D1, D2 and D3) which activates CDK4 and CDK6, and E-type (cyclins E1 and E2) which activate CDK2 and CDK1...
  5. Mip/LIN9 and Cell Proliferation
    Oscar R Colamonici; Fiscal Year: 2012
    ..CDK4,6 and CDK2 are responsible for the inactivation of the repressor activity that pRB/E2F1-3 and p107,p130/E2F4,5 exert on genes ..
  6. The CAK Network in Metazoan Cell Cycle Regulation
    Robert P Fisher; Fiscal Year: 2010
    ..Cdk7 is required for the activation of Cdk2, the major CDK active in S phase;and for the assembly and activation of Cdk1/cyclin B, the enzymatic trigger of ..
  7. JASON A CHESNEY; Fiscal Year: 2015
    ..the requirement of CDK1 for the pro-proliferative effects of PFKFB3 by demonstrating that CDK1 siRNA but not CDK2, CDK4 or CDK6 siRNA reversed the increased proliferation caused by over-expression of PFKFB3...
  8. Andrei Goga; Fiscal Year: 2014
    ..CDK1 and CDK2 are thought to be particularly important for driving the major cell cycle events in normal and neoplastic mammalian ..
  9. Chou Zen Giam; Fiscal Year: 2014
    ..subunit of another E3 ubiquitin ligase known as SCFSkp2, which mediates the destruction of cyclin E/A-CDK2 inhibitor (CKI), p27...
  10. Robert P Fisher; Fiscal Year: 2016
    ..Gene knockout and silencing studies suggested redundancy in the CDK network, by showing that Cdk2-long thought to be the principal driver of DNA synthesis (S) phase-was dispensable for viability...
  11. Chou Zen Giam; Fiscal Year: 2014
    ..the substrate-targeting subunit of another E3 ligase known as SCFSkp2, which mediates the destruction of cyclin E/A-CDK2 inhibitor (CKI), p27...
  12. Prevention of acute GvHD by inhibition of cdk2
    Vassiliki A Boussiotis; Fiscal Year: 2012
    ..The present exploratory study will test the hypothesis that inhibition of cdk2 is a novel strategy to prevent GvHD...
  13. Deregulated lipid metabolism in stroke
    Robert J Dempsey; Fiscal Year: 2013
    ..by (a) activating protein phosphatases 1 and 2A (PP1 and PP2A), (b) dephosphorylation of retinoblastoma (Rb) and Cdk2 and (c) up-regulation of Cdk inhibitors p21 and p27...
  14. Peter Sicinski; Fiscal Year: 2016
    ..Cyclin A2, together with its catalytic partners Cdk1 and Cdk2 is thought to drive S-phase progression by phosphorylating key proteins involved in DNA replication...
  15. ROCK II-mediated regulation of centrosome duplication / centrosome amplification
    Kenji Fukasawa; Fiscal Year: 2013
    ..NPM/B23 is one of the major targets of CDK2-cyclin E, which plays a key role in initiating centrosome duplication...
  16. Molecular mechanisms of C/EBP alpha mediated growth arrest
    Nikolai A Timchenko; Fiscal Year: 2013
    ..Cyclin D3-cdk4 phosphorylates C/EBP1 at Ser193 and increases its interactions with cdk2 and Brm resulting in the inhibition of cell proliferation...
  17. CYCLIN/CDK SUBSTRATES ESSENTIAL FOR G1 AND S PHASE
    James Roberts; Fiscal Year: 1999
    ..For example, complexes containing the D-type cyclins and Cdk4, and ones containing cyclin E and Cdk2 are both necessary and rate-limiting for completion of G1, whereas the cyclin B-Cdc2 complex is essential for ..
  18. The Oncogenic Significance of Cyclin Overexpression and Smad 3 Tumor Suppression
    Jacqueline Sara Jeruss; Fiscal Year: 2012
    ..Aim 3: Investigate the expression patterns of Smad 3, cyclin D, cyclin E, CDK4 and CDK2 in grades 1, 2, and 3 human breast cancer tissues, basal-like breast cancers, and normal mammary tissue...
  19. Normal and Neoplastic Regulation of Cyclin E
    Bruce E Clurman; Fiscal Year: 2013
    Cyclin E, in conjunction with its catalytic partner CDK2, regulates diverse aspects of cell division...
  20. Debra J Wolgemuth; Fiscal Year: 2016
    ..candidate testicular substrates of cyclin A1 and cyclin A2 complexed with their catalytic partners CDK1 and CDK2. This will be accomplished by fractionating lysates from spermatocytes and immature testes and subjecting them to ..
  21. Markers of sensivity to the EGFR inhibitor erlotinib in breast cancer
    Naoto T Ueno; Fiscal Year: 2012
    ..shown that in vitro erlotinib sensitivity is partially dependent on the activity of cyclin-dependent kinase 2 (Cdk2), which is the most downstream kinase of the EGFR pathway that regulates the transition from the G1 phase to the S ..
  22. James A Borowiec; Fiscal Year: 2014
    ..exploring the cis pathway, we will test the hypothesis that S33 phosphorylation facilitates recruitment of cyclin A-Cdk2 to the RPA substrate in vitro...
  23. Wenyi Wei; Fiscal Year: 2015
    ..We will further define how sequential phosphorylation of Cdh1 by Cyclin A/Cdk2 and Plk1 triggers the interaction with, and subsequent ubiquitination, by ?-TRCP...
  24. Andreas Friedl; Fiscal Year: 2016
    ..loop, which is characterized by the coordinated induction of E2F, Skp2, cyclin E and cyclin-dependent kinase 2 (CDK2) and the suppression of the cyclin-dependent kinase inhibitors (CKIs) p21 and p27...
  25. Khandan Keyomarsi; Fiscal Year: 2015
    ..I trial with dose expansion to determine maximum tolerated dose (MTD), response rate (RR) and biologic effects of CDK2 inhibition with roscovitine (Seliciclib) given prior to liposomal doxorubicin in patients with metastatic TNBC...
  26. Victoria L Bautch; Fiscal Year: 2016
    ..in blood vessels exposed to elevated VEGF-A signaling have excess centrosomes, mediated through Akt, MEK/ERK, and Cdk2/cyclin E...
  27. Cdk-2 Independent role of cyclin E in Cell survival
    Alexandru Almasan; Fiscal Year: 2013
    ..CycE cleavage generates p18CycE, which is unable to bind Cdk2 or other known interactors of CycE...
  28. Jennifer A Sanders; Fiscal Year: 2016
    ..of components of cyclin E complexes that regulate activity of the cyclin E effector, cyclin- dependent kinase 2 (CDK2)...
  29. Greenfield Sluder; Fiscal Year: 2014
    ..In Aim 3 we test if targeting of Cdk2-cyclin E to the centrosome is required for centrosome duplication or if soluble pools of this kinase complex are ..
  30. Cell Cycle Regulation of Histone Gene Expression
    Gary S Stein; Fiscal Year: 2013
    ..HiNF-P as the principal transcriptional regulator of histone genes, the end-point molecule for the cyclin E/ CDK2/ p220NPAT pathway, and HiNF-P deficiency impairs cell cycle progression through S phase...
  31. HARRIS R PERLMAN; Fiscal Year: 2014
    ..Further, CDK2, a target for p21, is constitutively active in p21-/- macrophages while CDK4 is induced in Wt and p21-/- ..
  32. MOUSE MODELS TO STUDY GONADAL TUMOR DEVELOPMENT
    Martin M Matzuk; Fiscal Year: 2010
    ..g., cyclin D2/CDK4, cyclin E2(E1)/CDK2, and p27) and inhibin determines the proliferation and terminal differentiation of granulosa or Sertoli cells, ..
  33. Examining the cell cycle-dependence of progesterone receptor activity
    LINDSEY STARR TREVINO; Fiscal Year: 2013
    ..Furthermore, our studies suggest that cyclin A/Cdk2/Cdk1 activity plays a role in S-phase gene expression...
  34. Targeting of 6-Phosphofructo-2 kinase in Cancer
    Jason Chesney; Fiscal Year: 2009
    ..Cdk1 and Cdk2 are essential mammalian cell cycle regulators that promote cell cycle progression in part by phosphorylating cell ..
  35. Peter M Price; Fiscal Year: 2014
    ..We have established that inhibition of a cell cycle-associated enzyme,cyclin-dependentkinase-2 (Cdk2), protects from cytotoxicity in vitro and protects from kidney injury in vivo caused by cisplatin administration...
  36. Wenyi Wei; Fiscal Year: 2016
    ..Moreover, depletion of Cyclin A or Cdk2 dramatically reduces Akt activity, suggesting that Cdk2/Cyclin A inhibitors may specifically kill breast cancer ..
  37. Phosphorylation of CDK9 by CDK2 in HIV-1 replication
    Denitra Breuer; Fiscal Year: 2011
    ..Our lab has previously shown that cell-cycle dependent kinase 2 (CDK2) phosphorylates HIV-1 Tat and that inhibition of this phosphorylation through the mutation of Tat or inactivation ..
  38. Role of Polyamines in MYCN-Amplified Neuroblastoma
    ANDRE BACHMANN; Fiscal Year: 2009
    ..and spermine) on the regulation and phosphorylation/activation of key signaling proteins including MYCN, p27Kip1, Cdk2, Akt, and mTOR...
  39. Effect of Iron Chelators on HIV-1 transcription
    ZUFAN KEREGO DEBEBE; Fiscal Year: 2011
    ..Our lab has previously shown that cyclin dependent kinase 2 (CDK2)/cyclin T1 is important for HIV-1 transcription...
  40. Regulation of the Mps1 Protein Kinase and Centrosome Duplication
    Harold A Fisk; Fiscal Year: 2012
    ..cell cycle events, the duplication of centrosomes is temporally restricted by cyclin-dependent kinase activity (Cdk2 in vertebrate cells)...
  41. Julie Horowitz; Fiscal Year: 2015
    ..I will then investigate if non-core Rag1 regions promote NF[unreadable]B-dependent activation of the CDK2-AP1 cell cycle checkpoint protein to prevent unrepaired RAG DSBs from entering the cell cycle by knocking down and ..
  42. PROLIFERATIVE EFFECTS OF CDK4 AND CDK6 DYSREGULATION
    Philip Hinds; Fiscal Year: 2006
    ..and, with cdks, to act as a "sink" for p21 and p27, inhibitory proteins that prevent the activity of cyclin E/cdk2. Moreover, it has been proposed based on experiments in cells lacking p21 and p27 and in mice expressing cyclin E ..
  43. The Role of Cyclin A in Cardiac Development
    HINA CHAUDHRY; Fiscal Year: 2006
    ..aim seeks to characterize molecular events that occur downstream of cyclin A binding to its kinase partners, cdk2 and cdc2...
  44. Ah Receptor Anatomy: Implications for Dioxin Toxicity
    CORNELIS JOHAN ELFERINK; Fiscal Year: 2011
    ..the planned studies will examine the molecular basis and relative contribution of cyclin-dependent kinase 2 (CDK2) inhibi- ion and plasminogen activator inhibitor-1 (PAI-1) expression on liver regeneration...
  45. Inhibitors of disease-promoting activities of senescence
    DONALD PORTER; Fiscal Year: 2009
    ..this project revealed that SNX2-class compounds affect CKI interaction with cyclin/CDK complexes in such a way that CDK2 kinase activity becomes much more susceptible to the inhibition by CKI, whereas transcriptional activation by CKI ..
  46. CDK3-inhibiting anticancer agents
    Donald C Porter; Fiscal Year: 2012
    ..This tumor selectivity advantageously distinguishes CDK3 as a cancer target from cell cycle-regulating CDKs (CDK1, CDK2, CDK4/6), which are targeted by pharmaceutical CDK inhibitors, previously developed by others...
  47. CDK6 in T cell development and cancer
    Philip W Hinds; Fiscal Year: 2013
    ..loss may be ascribed to compensation, since "free" D-type cyclins in cdk4/6 knockout cells appear able to activate cdk2 to allow proliferation...
  48. Steven F Dowdy; Fiscal Year: 2014
    ..We will isolate the Low Mw CAK complex from Panc1 pancreatic cancer cells that contain constitutively active Cdk2, and hence, by definition, also contain constitutively express CAK, and identify it's sequence by mass ..
  49. Cyclin-dependent Kinase Inhibitor In Acute Renal Failure
    Peter M Price; Fiscal Year: 2013
    ..We have established that inhibition of a cell cycle-associated enzyme, cyclin-dependent kinase-2 (Cdk2), protect from cytotoxicity in vitro and protects from kidney injury in vivo caused by cisplatin administration...
  50. Steven I Reed; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): Cyclin E, an activator of cyclin-dependent kinase 2 (Cdk2) is a positive activator of the G1-S phase transition in proliferating mammalian cells and therefore serves an important function during ..
  51. Effect of Cdk inhibitor on HIV-1 replication
    Fatah Kashanchi; Fiscal Year: 2007
    ..natural cyclin dependent kinase (cdk) inhibitors, and in turn is able to control the primary cdk targets such as cdk2/cyclin E complex...
  52. Haojie Huang; Fiscal Year: 2016
    ..We also demonstrate that CDK1 and CDK2, two key kinases involved in both cell cycle regulation and response to genotoxic stress, interact with and ..
  53. Mechanisms of cyclin E associated tumorigenesis
    ALEXANDER MINELLA; Fiscal Year: 2007
    unreadable] DESCRIPTION (provided by applicant): Cyclin E, with its partner kinase Cdk2, controls cell cycle progression from G1 to S phase...
  54. EBNA3C and tumor supressors
    Erle S Robertson; Fiscal Year: 2010
    ..We will investigate the phosphorylation status of p53 by kinases which include CyclinA/Cdk2, Chk1, Chk2 and ATM which prevents Mdm2 targeted ubiquitination and test the ability of EBNA3C to modulate the ..
  55. A Neoadjuvant Trial of Anastrazole and A Novel SRC Inhibitor, AZD0530, for LABC
    JOYCE MARIE contact SLINGERLAND; Fiscal Year: 2010
    ..Her2 or Src activation in ER+ breast cancer cells alters p27 phosphorylation, impairs its Cdk2 inhibitory function and causes antiestrogen resistance...
  56. Novel ways of regulating cyclin E in cancer
    REBECCA HARTLEY; Fiscal Year: 2007
    ..G1) to the DNA synthesis phase (S) when it binds to and activates its kinase partner, cyclin-dependent kinase 2 (cdk2)...
  57. CDK Inhibition in Cancer
    Andrei Goga; Fiscal Year: 2009
    ..b>Cdk2 and Cdk1 are generally thought to control the S and M phases of the vertebrate cell cycle, respectively...
  58. Esteban A Terzo; Fiscal Year: 2015
    ..In addition, HLBs are regulated in a cell cycle-dependent manner, as Mxc is subjected to CycE/Cdk2-dependent phosphorylation during S phase, as is its human orthologue, NPAT...
  59. THERAPEUTIC IMPLICATIONS AND MECHANISMS OF CYCLIN E
    Khandan Keyomarsi; Fiscal Year: 2000
    ..Cyclin E, a regulatory subunit of cyclin-dependent kinase-2 (cdk2), is thought to be rate limiting for the G1/S transition during the mammalian cell cycle...
  60. PROGESTERONE, CELL CYCLE AND CANCER
    Jeffrey Pollard; Fiscal Year: 2005
    ..These include the cyclin D-Cdk4 and cyclin D-Cdk6 complexes acting early in G1 and the cyclin E-Cdk2 complex acting at the G1 to S-phase boundary...
  61. P27Kipl deficiency, potential promoter of carcinogenesis
    Konstantin Christov Tzelkov; Fiscal Year: 2003
    ..P27/Kip1 is a cell cycle suppressor that inhibits cyclin D1-D3/cdk4 and or cyclin E/cdk2 activity in the G1 phase of the cell cycle and thus prevents the G1-S transition and cell-type progression...
  62. GROWTH REGULATION--SENESCENT VS NONSENESCENT CELLS
    GRETCHEN STEIN; Fiscal Year: 1999
    ..In addition, preliminary results indicate that mitogen-stimulated senescent HDF have less cdk2 mRNA than do comparably treated quiescent HDF...
  63. Function of Nucleophosmin/B23 in Centrosome Duplication
    Kenji Fukasawa; Fiscal Year: 2006
    ..Because CDK2/cyclin E also drives cells to initiate DNA synthesis, the temporal activation of CDK2/cyclin E occurring in the mid-..
  64. Cables role in endometrial differentiation and cancer
    Bo Rueda; Fiscal Year: 2007
    ..b>Cdk2 regulates the G1 S-phase transition of the cell cycle and cdk2 tyrosine phosphorylation is inhibitory and leads to ..