Summary: Regulatory proteins that function in the cell cycle to activate maturation promoting factor. They complex with p34cdc2 (PROTEIN P34CDC2), the catalytic subunit of MATURATION-PROMOTING FACTOR, and modulate its protein kinase activity. Cyclins themselves have no enzymatic activity.

Top Publications

  1. ncbi The role of the cyclin-dependent kinase inhibitor p21 in apoptosis
    Andrei L Gartel
    Department of Molecular Genetics, University of Illinois College of Medicine, Chicago, Illinois 60607, USA
    Mol Cancer Ther 1:639-49. 2002
  2. 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
  3. ncbi WAF1, a potential mediator of p53 tumor suppression
    W S El-Deiry
    Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231
    Cell 75:817-25. 1993
  4. 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
  5. 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
  6. ncbi Principles of CDK regulation
    D O Morgan
    Department of Physiology, University of California, San Francisco 94143 0444
    Nature 374:131-4. 1995
  7. 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
  8. 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
  9. ncbi Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms
    A Satyanarayana
    Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute Frederick, Frederick, MD 21702 1201, USA
    Oncogene 28:2925-39. 2009
  10. ncbi 7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes
    V T Nguyen
    Genetique Moleculaire, UMR 8541 CNRS, Ecole Normale Superieure, 46 rue d Ulm, 75230 Paris Cedex 05, France
    Nature 414:322-5. 2001

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Detail Information

Publications339 found, 100 shown here

  1. ncbi The role of the cyclin-dependent kinase inhibitor p21 in apoptosis
    Andrei L Gartel
    Department of Molecular Genetics, University of Illinois College of Medicine, Chicago, Illinois 60607, USA
    Mol Cancer Ther 1:639-49. 2002
    ..In the current review, we discuss the role of p21 in regulating cell death and the potential relevance of its expression in cancer...
  2. 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...
  3. ncbi WAF1, a potential mediator of p53 tumor suppression
    W S El-Deiry
    Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231
    Cell 75:817-25. 1993
    ..These studies define a gene whose expression is directly induced by p53 and that could be an important mediator of p53-dependent tumor growth suppression...
  4. 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
    The cyclin-dependent kinase Cdk2 associates with cyclins A, D, and E and has been implicated in the control of the G1 to S phase transition in mammals...
  5. 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...
  6. ncbi Principles of CDK regulation
    D O Morgan
    Department of Physiology, University of California, San Francisco 94143 0444
    Nature 374:131-4. 1995
    ..The activity of cyclin-dependent kinases is controlled by four highly conserved biochemical mechanisms, forming a web of regulatory pathways unmatched in its elegance and intricacy...
  7. 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
    ..The complexes formed by CDK4 and the D-type cyclins have been strongly implicated in the control of cell proliferation during the G1 phase...
  8. 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...
  9. ncbi Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms
    A Satyanarayana
    Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute Frederick, Frederick, MD 21702 1201, USA
    Oncogene 28:2925-39. 2009
    ..Several unexpected compensatory mechanisms were uncovered among cyclins and Cdks in these studies...
  10. ncbi 7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes
    V T Nguyen
    Genetique Moleculaire, UMR 8541 CNRS, Ecole Normale Superieure, 46 rue d Ulm, 75230 Paris Cedex 05, France
    Nature 414:322-5. 2001
    ..The transcription-dependent interaction of P-TEFb with 7SK may therefore contribute to an important feedback loop modulating the activity of RNA Pol II...
  11. ncbi Cdks, cyclins and CKIs: roles beyond cell cycle regulation
    Shuhui Lim
    Institute of Molecular and Cell Biology IMCB, A STAR Agency for Science, Technology and Research, Singapore 138673, Republic of Singapore
    Development 140:3079-93. 2013
    ..kinases (Cdks) are serine/threonine kinases and their catalytic activities are modulated by interactions with cyclins and Cdk inhibitors (CKIs)...
  12. 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 interacts strongly with D-type cyclins and Cdk4 in vitro and more weakly with cyclin E and Cdk2...
  13. ncbi p53-dependent and independent expression of p21 during cell growth, differentiation, and DNA damage
    K F Macleod
    Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139, USA
    Genes Dev 9:935-44. 1995
    ..Moreover, p21 can be regulated independently of p53 in several situations including during normal tissue development, following serum stimulation, and during cellular differentiation...
  14. ncbi The effects of molecular noise and size control on variability in the budding yeast cell cycle
    Stefano Di Talia
    The Rockefeller University, New York, New York 10021, USA
    Nature 448:947-51. 2007
    ..Also, increasing the gene dosage of G1 cyclins decreases the variability in G1...
  15. ncbi Cln3 activates G1-specific transcription via phosphorylation of the SBF bound repressor Whi5
    Robertus A M de Bruin
    Department of Molecular Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Cell 117:887-98. 2004
    ..Like mammalian Rb, Whi5 is a G1-specific transcriptional repressor antagonized by CDK...
  16. ncbi Cdk1 is sufficient to drive the mammalian cell cycle
    David Santamaria
    Molecular Oncology Programme, Centro Nacional de Investigaciones Oncologicas, E 28029 Madrid, Spain
    Nature 448:811-5. 2007
    ..results have been obtained on ablation of some of the activating subunits of Cdks, such as the D-type and E-type cyclins. Here we show that mouse embryos lacking all interphase Cdks (Cdk2, Cdk3, Cdk4 and Cdk6) undergo organogenesis ..
  17. pmc Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization
    J A Diehl
    Howard Hughes Medical Institute, St Jude Children s Research Hospital, Memphis, Tennessee 38105 USA
    Genes Dev 12:3499-511. 1998
    ..Induction of D-type cyclins and their assembly into holoenzyme complexes depend on mitogen stimulation...
  18. ncbi SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box
    C Bai
    Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA
    Cell 86:263-74. 1996
    ..Different skp1 mutants arrest cells in either G1 or G2, suggesting a connection between regulation of proteolysis in different stages of the cycle...
  19. 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...
  20. ncbi F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex
    D Skowyra
    Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030, USA
    Cell 91:209-19. 1997
    ..SCF complexes couple protein kinase signaling pathways to the control of protein abundance...
  21. 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...
  22. pmc A quantitative model for cyclin-dependent kinase control of the cell cycle: revisited
    Frank Uhlmann
    Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3LY, UK
    Philos Trans R Soc Lond B Biol Sci 366:3572-83. 2011
    ..Alternative mechanisms for ordering have been proposed that rely on checkpoint controls or on sequential waves of cyclins with distinct substrate specificities...
  23. pmc OSD1 promotes meiotic progression via APC/C inhibition and forms a regulatory network with TDM and CYCA1;2/TAM
    Laurence Cromer
    INRA, UMR1318, Institut Jean Pierre Bourgin, Versailles, France
    PLoS Genet 8:e1002865. 2012
    ..We thus propose that a functional network composed of OSD1, CYCA1;2/TAM, and TDM controls three key steps of meiotic progression, in which OSD1 is a meiotic APC/C inhibitor...
  24. 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
    The association of cdk4 with D-type cyclins to form functional kinase complexes is comparatively inefficient. This has led to the suggestion that assembly might be a regulated step...
  25. ncbi Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells
    B P Zhou
    Department of Molecular and Cellular Oncology, Breast Cancer Basic Research Program, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA
    Nat Cell Biol 3:245-52. 2001
    ..Our results indicate that HER-2/neu induces cytoplasmic localization of p21Cip1/WAF1 through activation of Akt to promote cell growth, which may have implications for the oncogenic activity of HER-2/neu and Akt...
  26. ncbi p21 is a universal inhibitor of cyclin kinases
    Y Xiong
    Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724
    Nature 366:701-4. 1993
    ..Furthermore, overexpression of p21 inhibits the proliferation of mammalian cells. Our results indicate that p21 may be a universal inhibitor of cyclin kinases...
  27. ncbi Cyclins and cdks in development and cancer: a perspective
    Amit Deshpande
    Department of Radiation Oncology, Molecular Oncology Research Institute, Tufts New England Medical Center, Boston, MA 02111, USA
    Oncogene 24:2909-15. 2005
  28. 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...
  29. 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
    ..Although several cyclins and associated cyclin-dependent kinases (cdks) have been implicated in pRb phosphorylation, the precise mechanism ..
  30. 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
    ..or cyclosome, initiates chromosome segregation and exit from mitosis by degrading anaphase inhibitors and mitotic cyclins. Proteolysis therefore drives cell cycle progression not only by regulating CDK activity, but by directly ..
  31. pmc MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-dependent manner
    Annemieke A Michels
    UMR 8541 CNRS, Ecole Normale Superieure, Laboratoire de Régulation de l Expression Génétique, 75230 Paris Cedex 05, France
    Mol Cell Biol 23:4859-69. 2003
    ..from extracts of transfected cells, MAQ1 binds directly to the N-terminal cyclin homology region of cyclins T1 and T2...
  32. pmc A high throughput genetic screen identifies new early meiotic recombination functions in Arabidopsis thaliana
    Arnaud De Muyt
    INRA de Versailles, Institut Jean Pierre Bourgin, Station de Génétique et d Amélioration des Plantes UR 254, Versailles, France
    PLoS Genet 5:e1000654. 2009
    ..Unlike SPO11 and (to a minor extent) PRD1, these two new proteins are poorly conserved among species, suggesting that the DSB formation mechanism, but not its regulation, is conserved among eukaryotes...
  33. ncbi Cyclin E and survival in patients with breast cancer
    Khandan Keyomarsi
    Department of Experimental Radiation Oncology, University of Texas M D Anderson Cancer Center, Houston 77030 4095, USA
    N Engl J Med 347:1566-75. 2002
    ..Cyclin E, a regulator of the cell cycle, affects the behavior of breast-cancer cells. We investigated whether levels of cyclin E in the tumor correlated with survival among patients with breast cancer...
  34. pmc Induction of TAK (cyclin T1/P-TEFb) in purified resting CD4(+) T lymphocytes by combination of cytokines
    R Ghose
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Virol 75:11336-43. 2001
    ..These results suggest that induction of TAK by cytokines secreted in the microenvironment of lymphoid tissue may be involved in the reactivation of HIV-1 in CD4(+) T lymphocytes harboring a latent provirus...
  35. pmc TOR controls translation initiation and early G1 progression in yeast
    N C Barbet
    Department of Biochemistry, University of Basel, Switzerland
    Mol Biol Cell 7:25-42. 1996
    ..Such a pathway may constitute a checkpoint that prevents early G1 progression and growth in the absence of nutrients...
  36. ncbi p53-independent expression of p21Cip1 in muscle and other terminally differentiating cells
    S B Parker
    Department of Biochemistry, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030
    Science 267:1024-7. 1995
    ..The p21 protein may function during development as an inducible growth inhibitor that contributes to cell cycle exit and differentiation...
  37. pmc Physical interaction of human T-cell leukemia virus type 1 Tax with cyclin-dependent kinase 4 stimulates the phosphorylation of retinoblastoma protein
    Kerstin Haller
    Institut fur Klinische und Molekulare Virologie, D 91054 Erlangen, Germany
    Mol Cell Biol 22:3327-38. 2002
    ..Thus, protein-protein contact between Tax and the components of the cyclin D/CDK complexes provides a further mechanistic explanation for the mitogenic and immortalizing effects of this HTLV-1 oncoprotein...
  38. ncbi Flavopiridol inhibits P-TEFb and blocks HIV-1 replication
    S H Chao
    Molecular Biology Program and the Department of Biochemistry, University of Iowa, Iowa City, Iowa 52242, USA
    J Biol Chem 275:28345-8. 2000
    ..Furthermore, flavopiridol blocked HIV-1 replication in both single-round and viral spread assays with an IC(50) of less than 10 nm...
  39. ncbi Global analysis of the core cell cycle regulators of Arabidopsis identifies novel genes, reveals multiple and highly specific profiles of expression and provides a coherent model for plant cell cycle control
    Margit Menges
    Institute of Biotechnology, University of Cambridge, Tennis Court Road, CB2 1QT Cambridge, UK
    Plant J 41:546-66. 2005
    ..Alone amongst the six groups of A and B type cyclins, members of CYCA3 peak in S-phase suggest it is a major component of S-phase kinases, whereas others show a peak ..
  40. pmc Human cyclins A and B1 are differentially located in the cell and undergo cell cycle-dependent nuclear transport
    J Pines
    Molecular Biology and Virology Laboratory, Salk Institute for Biological Studies, San Diego, California 92186 5800
    J Cell Biol 115:1-17. 1991
  41. pmc Meiotic progression in Arabidopsis is governed by complex regulatory interactions between SMG7, TDM1, and the meiosis I-specific cyclin TAM
    Petra Bulankova
    Gregor Mendel Institute, Austrian Academy of Sciences, 1030 Viena, Austria
    Plant Cell 22:3791-803. 2010
    ..We propose a model that meiotic progression in Arabidopsis pollen mother cells is driven by a yet to be identified cyclin-CDK activity that is modulated by regulatory interactions between TDM1, SMG7, and TAM...
  42. ncbi Regulation of G(1) cyclin-dependent kinases in the mammalian cell cycle
    S V Ekholm
    Department of Oncology Pathology, Cancer Center Karolinska, Karolinska Insitutet, 17176, Stockholm, Sweden
    Curr Opin Cell Biol 12:676-84. 2000
    ..In mammalian cells, Cdk2, Cdk4, Cdk6 and associated cyclins control the G(1) to S phase transition...
  43. pmc Meiosis I is established through division-specific translational control of a cyclin
    Thomas M Carlile
    Center for Cancer Research, Massachusetts Institute of Technology, E17 233, 40 Ames Street, Cambridge, MA 02139, USA
    Cell 133:280-91. 2008
    ..Our results demonstrate an essential role for Clb-CDK regulation in establishing the meiotic chromosome segregation pattern...
  44. pmc A mechanism for cell-cycle regulation of MAP kinase signaling in a yeast differentiation pathway
    Shelly C Strickfaden
    Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Cell 128:519-31. 2007
    ..These findings define a mechanism and physiological benefit of restricting antiproliferative signaling to G1...
  45. pmc Differential function and expression of Saccharomyces cerevisiae B-type cyclins in mitosis and meiosis
    N Grandin
    Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037
    Mol Cell Biol 13:2113-25. 1993
    We have studied the patterns of expression of four B-type cyclins (Clbs), Clb1, Clb2, Clb3, and Clb4, and their ability to activate p34cdc28 during the mitotic and meiotic cell cycles of Saccharomyces cerevisiae...
  46. ncbi New insights into cyclins, CDKs, and cell cycle control
    Department of Pathology, MSB 504, New York University School of Medicine, NYU Cancer Institute, 550 First Avenue, New York, NY 10016, USA
    Semin Cell Dev Biol 16:311-21. 2005 catalytic subunit (cyclin-dependent kinase) that pairs with cell cycle-specific regulatory subunits known as cyclins. Progression through a specific phase of the cell cycle is under the control of a specific class of cyclin...
  47. ncbi New roles for p21 and p27 cell-cycle inhibitors: a function for each cell compartment?
    Olivier Coqueret
    INSERM U564, 4 rue Larrey, CHU Angers, France
    Trends Cell Biol 13:65-70. 2003
    Cell division relies on the activation of cyclins, which bind to cyclin-dependent kinases (CDKs) to induce cell-cycle progression towards S phase and later to initiate mitosis...
  48. 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...
  49. ncbi Resistance to Fas-mediated apoptosis: activation of caspase 3 is regulated by cell cycle regulator p21WAF1 and IAP gene family ILP
    A Suzuki
    Drug Safety Research Laboratory, Daiichi Pharmaceutical Co, Ltd, Tokyo R and D Center, Japan
    Oncogene 17:931-9. 1998
    ..Here we report that caspase 3 inactivation for the resistance to Fas-mediated apoptosis is induced by a procaspase 3/p21 complex formation and direct inhibition of activated caspase 3 by ILP...
  50. ncbi The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA
    S Waga
    Cold Spring Harbor Laboratory, New York 11724
    Nature 369:574-8. 1994
    ..Thus, during p53-mediated suppression of cell proliferation, p21 and PCNA may be important for coordinating cell-cycle progression, DNA replication and repair of damaged DNA...
  51. pmc Identification of multiple cyclin subunits of human P-TEFb
    J Peng
    Department of Biochemistry, University of Iowa, Iowa City, Iowa 52242, USA
    Genes Dev 12:755-62. 1998
    ..Cotransfection experiments indicated that all three CDK9/cyclin combinations dramatically activated the CMV promoter...
  52. ncbi A role for the transcription factors Mbp1 and Swi4 in progression from G1 to S phase
    C Koch
    Institute of Molecular Pathology, Vienna, Austria
    Science 261:1551-7. 1993
    In budding yeast genes that encode G1 cyclins and proteins involved in DNA synthesis are transcriptionally activated in late G1...
  53. ncbi Cdks and cyclins link G1 length and differentiation of embryonic, neural and hematopoietic stem cells
    Christian Lange
    Medical Faculty, DFG Research Center and Cluster of Excellence for Regenerative Therapies Dresden, Technische Universitat Dresden, Dresden, Germany
    Cell Cycle 9:1893-900. 2010
    ..In particular, we will discuss the effects of G1-cdks/cyclins on differentiation of embryonic, neural and hematopoietic stem cells during development and adulthood, for which ..
  54. ncbi Systems-level dissection of the cell-cycle oscillator: bypassing positive feedback produces damped oscillations
    Joseph R Pomerening
    Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305, USA
    Cell 122:565-78. 2005
    ..This work also underscores the fundamental similarity of cell-cycle oscillations in embryos to repetitive action potentials in pacemaker neurons, with both systems relying on a combination of negative and positive-feedback loops...
  55. pmc The structure of CDK4/cyclin D3 has implications for models of CDK activation
    T Takaki
    Cell Cycle Control Laboratory, Clare Hall Laboratories, London Research Institute, Blanche Lane, South Mimms, Herts EN6 3LD, United Kingdom
    Proc Natl Acad Sci U S A 106:4171-6. 2009
    ..Taken together, these results suggest that the structural mechanism of CDK4/cyclin D3 activation differs markedly from that of previously studied CDK/cyclin complexes...
  56. pmc Targeted interactomics reveals a complex core cell cycle machinery in Arabidopsis thaliana
    Jelle Van Leene
    Department of Plant Systems Biology, VIB, Ghent, Belgium
    Mol Syst Biol 6:397. 2010
    ..Important conclusions were that mitotic A- and B-type cyclins form complexes with the plant-specific B-type CDKs and not with CDKA;1, and that D-type cyclins and S-phase-..
  57. ncbi Identification of a cyclin T-binding domain in Hexim1 and biochemical analysis of its binding competition with HIV-1 Tat
    Antje Schulte
    Max Planck Institut fur molekulare Physiologie, Abteilung Physikalische Biochemie, Otto Hahn Strasse 11, D 44227 Dortmund, Germany
    J Biol Chem 280:24968-77. 2005
    ..Our data suggest a model where HIV-1 Tat competes with Hexim1 for cyclin T1 binding, thus releasing P-TEFb from the inactive complex to stimulate the transcription of HIV-1 gene expression...
  58. pmc Bortezomib stabilizes mitotic cyclins and prevents cell cycle progression via inhibition of UBE2C in colorectal carcinoma
    Prashant Bavi
    Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
    Am J Pathol 178:2109-20. 2011
    ..Altogether, our results suggest that UBE2C and the ubiquitin-proteasome pathway may be potential targets for therapeutic intervention in CRC...
  59. pmc Conserved CDC20 cell cycle functions are carried out by two of the five isoforms in Arabidopsis thaliana
    Zoltan Kevei
    Institut des Sciences du Vegetal, Centre National de la Recherche Scientifique, Unité Propre de Recherche 2355, Gif sur Yvette, France
    PLoS ONE 6:e20618. 2011
    ..In yeasts and animals the main CDC20 function is the destruction of securin and mitotic cyclins. Plants have multiple CDC20 gene copies whose functions have not been explored yet...
  60. ncbi Mitotic cyclins stimulate the activity of c-Myb-like factors for transactivation of G2/M phase-specific genes in tobacco
    Satoshi Araki
    Division of Biological Science, Graduate School of Science, Nagoya University, Furo cho, Chikusa ku, Nagoya 464 8602, Japan
    J Biol Chem 279:32979-88. 2004
    ..of NtmybA2 is repressed by a regulatory domain located at its carboxyl terminus and that specific classes of cyclins A and B enhanced NtmybA2 activity possibly by relieving this inhibitory effect...
  61. 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
    Cyclin-dependent kinases and cyclins regulate with the help of different interacting proteins the progression through the eukaryotic cell cycle...
  62. ncbi Mice lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control
    C Deng
    Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 82:675-84. 1995
    ..These results establish the role of p21CIP1/WAF1 in the G1 checkpoint, but suggest that the anti-apoptotic and the anti-oncogenic effects of p53 are more complex...
  63. 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
    ..efficiently phosphorylated the G1 peptide, RPPTLS780PIPHIPR that contained a part of the sequence of pRB, while cyclins E-Cdk2 and A-Cdk2 did not...
  64. ncbi Recycling the cell cycle: cyclins revisited
    Andrew W Murray
    Department of Molecular and Cellular Biology, Biological Laboratories, Harvard University, Cambridge, MA 02138, USA
    Cell 116:221-34. 2004
    ..The surprising redundancy amongst the classical cyclins (A, B, and E) and cyclin-dependent kinases (Cdk1 and Cdk2) show that the important differences between these ..
  65. 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...
  66. pmc Regulation of the cyclin E gene by transcription factor E2F1
    K Ohtani
    Department of Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 92:12146-50. 1995
    ..action of retinoblastoma protein (RB) and RB-related proteins and indirectly regulated through the action of G1 cyclins and associated kinases. We now show that the accumulation of G1 cyclins is regulated by E2F1...
  67. ncbi Molecular mechanism of cell cycle progression induced by the oncogene product Tax of human T-cell leukemia virus type I
    R Iwanaga
    Human Gene Sciences Center, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
    Oncogene 20:2055-67. 2001
    ..These results indicate the important role of Tax-mediated trans-activation of the genes for cell cycle regulatory molecules in Tax-induced cell cycle progression...
  68. ncbi Caspase-mediated cleavage of p21Waf1/Cip1 converts cancer cells from growth arrest to undergoing apoptosis
    Y Zhang
    Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan
    Oncogene 18:1131-8. 1999
    ..Thus, caspase-3-mediated cleavage and inactivation of p21 protein may convert cancer cells from growth arrest to undergoing apoptosis, leading to the acceleration of chemotherapy-induced apoptotic process in cancer cells...
  69. ncbi Genome-wide identification and expression analysis of rice cell cycle genes
    Jing Guo
    Shandong Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, Taian, Shandong, 271018, China
    Plant Mol Biol 64:349-60. 2007
    b>Cyclins, cyclin-dependent kinases, and a number of other proteins control the progression of plant cell cycle...
  70. ncbi Requirement for cyclin D3 in lymphocyte development and T cell leukemias
    Ewa Sicinska
    Department of Cancer Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 4:451-61. 2003
    The D-type cyclins (cyclins D1, D2, and D3) are components of the core cell cycle machinery in mammalian cells. Cyclin D3 gene is rearranged and the protein is overexpressed in several human lymphoid malignancies...
  71. ncbi Blocking of FGFR signaling inhibits breast cancer cell proliferation through downregulation of D-type cyclins
    Magdalena Koziczak
    Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH 4058 Basel, Switzerland
    Oncogene 23:3501-8. 2004
    ..Our analyses revealed that FGFR signaling links to the cell cycle machinery via D-type cyclins. PD173074-mediated inhibition of FGFR activity caused downregulation of cyclin D1 and cyclin D2 expression, ..
  72. ncbi MicroRNA-15b regulates cell cycle progression by targeting cyclins in glioma cells
    Hongping Xia
    Integrative Chemical Biology Laboratory, Institute of Molecular Technology, Department of Chemistry, 8 F, Kadoorie Biological Science Building, The University of Hong Kong, Pokfulam Road, Hong Kong, China
    Biochem Biophys Res Commun 380:205-10. 2009
    ..We further showed that CCNE1 (encoding cyclin E1) is one of the downstream targets of miR-15b. Taken together, our findings indicate that miR-15b regulates cell cycle progression in glioma cells by targeting cell cycle-related molecules...
  73. ncbi Specific regulation of cyclins D1 and D2 by FGF and Shh signaling coordinates cell cycle progression, patterning, and differentiation during early steps of spinal cord development
    Valerie Lobjois
    Centre de Biologie du Developpement, CNRS UMR5547 Bât 4R3, 31062 Toulouse Cedex, France
    Dev Biol 273:195-209. 2004
    ..Here we investigated the integration of D-type cyclins, known to govern cell cycle progression under the control of extracellular signals, in the program of spinal cord ..
  74. pmc Hgc1, a novel hypha-specific G1 cyclin-related protein regulates Candida albicans hyphal morphogenesis
    Xinde Zheng
    Institute of Molecular and Cell Biology, Singapore, Singapore
    EMBO J 23:1845-56. 2004
    ..C. albicans seems to have adapted a conserved strategy to control specifically hyphal morphogenesis...
  75. 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...
  76. 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
    ..Here it is reported that PHO80 has homology to yeast cyclins and interacts with PHO85, a p34cdc2/CDC28-related protein kinase...
  77. pmc Regulated activating Thr172 phosphorylation of cyclin-dependent kinase 4(CDK4): its relationship with cyclins and CDK "inhibitors"
    Laurence Bockstaele
    Institute of Interdisciplinary Research, Universite Libre de Bruxelles, Campus Erasme, B 1070 Brussels, Belgium
    Mol Cell Biol 26:5070-85. 2006
    ..of CDK4 activation remain poorly known or debated, including the regulation of its association with D-type cyclins, its activating Thr172 phosphorylation, and the roles of Cip/Kip CDK "inhibitors" in these processes...
  78. ncbi The carboxyl-terminal fragment of pro-HB-EGF reverses Bcl6-mediated gene repression
    Yumi Kinugasa
    Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Shitsukawa, To on, Ehime 791 0295, Japan
    J Biol Chem 282:14797-806. 2007
    ..These findings suggest that HB-EGF-CTF is a potent regulator of gene expression via its interaction with the transcriptional repressor Bcl6...
  79. ncbi The coupling of cell growth to the cell cycle
    N Tapon
    Massachusetts General Hospital Cancer Center, Building 149, 13th Street, Charlestown, MA 02129, USA
    Curr Opin Cell Biol 13:731-7. 2001
    ..This work has revealed interesting and unexpected relationships between mechanisms that regulate growth and the cell cycle machinery...
  80. 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
    ..These data suggest that cdk2 activation, through caspase-mediated cleavage of cdk inhibitors, may be instrumental in the execution of apoptosis following caspase activation...
  81. ncbi Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers
    T Nobori
    Department of Medicine, University of California, San Diego, La Jolla 92093 0663
    Nature 368:753-6. 1994
    ..The CDK4 inhibitor is thought to be a physiological suppressor of proliferation. Cells unable to produce the inhibitor may be prone to neoplastic transformation...
  82. ncbi MYC accelerates p21CIP-induced megakaryocytic differentiation involving early mitosis arrest in leukemia cells
    Maria J Munoz-Alonso
    Departamento de Biologia Molecular, Universidad de Cantabria, Santander, Spain
    J Cell Physiol 227:2069-78. 2012
    ..Transient overexpression of p21(CIP) caused early down-regulation of mitotic Cyclins and up-regulation of G1/S Cyclins D and E, changes typical of endoreplication...
  83. pmc The transcriptional network activated by Cln3 cyclin at the G1-to-S transition of the yeast cell cycle
    Francisco Ferrezuelo
    Departament de Ciencies Mediques Basiques, Institut de Recerca Biomedica de Lleida, Universitat de Lleida, Montserrat Roig 2, 25008 Lleida, Spain
    Genome Biol 11:R67. 2010
    ..Activation of these factors ultimately depends on the G1 cyclin Cln3...
  84. ncbi Asymmetric loading of Kar9 onto spindle poles and microtubules ensures proper spindle alignment
    Dimitris Liakopoulos
    Institute of Biochemistry, Swiss Federal Institute of Technology, ETH Hoenggerberg, HPM, CH 8093 Zurich, Switzerland
    Cell 112:561-74. 2003
    ..In turn, asymmetric distribution of Kar9 ensures that only one pole orients toward the bud. Our results indicate that Cdk1-dependent spindle asymmetry ensures proper alignment of the mitotic spindle with the cell division axis...
  85. ncbi Specific chemopreventive agents trigger proteasomal degradation of G1 cyclins: implications for combination therapy
    Konstantin H Dragnev
    Norris Cotton Cancer Center, and Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Clin Cancer Res 10:2570-7. 2004
    ..G(1) arrest was triggered by cyclin D1 proteolysis via ubiquitin-dependent degradation. This study investigated which chemopreventive agents activated this degradation program and whether cyclin E was also degraded...
  86. pmc A pcl-like cyclin activates the Res2p-Cdc10p cell cycle "start" transcriptional factor complex in fission yeast
    K Tanaka
    Department of Biochemistry and Molecular Biology, The University of Tokyo, Graduate School of Medicine, Bunkyo ku, Tokyo 113 0033, Japan
    Mol Biol Cell 11:2845-62. 2000
    ..This gene encodes a novel cyclin that shares homology with the Pho85 kinase-associated cyclins of the budding yeast Saccharomyces cerevisiae...
  87. pmc Cyclins D2 and D1 are essential for postnatal pancreatic beta-cell growth
    Jake A Kushner
    Division of Endocrinology, Children s Hospital of Philadelphia, 3615 Civic Center Blvd, Philadelphia, PA 19104, USA
    Mol Cell Biol 25:3752-62. 2005
    ..In many tissues mitogens influence development by stimulating D-type cyclins (D1, D2, or D3) and activating cyclin-dependent kinases (CDK4 or CDK6), which results in progression through the ..
  88. ncbi Cell cycle control of wnt receptor activation
    Gary Davidson
    Division of Molecular Embryology, Karlsruhe Institute of Technology, Institute of Toxicology and Genetics, Hermann von Helmholtz Platz 1, 76344 Eggenstein Leopoldshafen, Germany
    Dev Cell 17:788-99. 2009
    ..G2/M priming of LRP6 by a Cyclin/CDK complex introduces an unexpected new layer of regulation of Wnt signaling...
  89. ncbi Hematopoietic stem cell quiescence maintained by p21cip1/waf1
    T Cheng
    Experimental Hematology, AIDS Research Center, Massachusetts General Hospital Cancer Center, Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
    Science 287:1804-8. 2000
    ..Under conditions of stress, restricted cell cycling is crucial to prevent premature stem cell depletion and hematopoietic death...
  90. ncbi Evidence for different modes of action of cyclin-dependent kinase inhibitors: p15 and p16 bind to kinases, p21 and p27 bind to cyclins
    M Hall
    Molecular Oncology Laboratory, Imperial Cancer Research Fund, London
    Oncogene 11:1581-8. 1995
    ..a simple in vitro binding assay, we show that p21CDKN1 and the related p27KIP1 can efficiently interact with cyclins D1, D2, D3, E and A, and to a lesser extent with cyclin B...
  91. ncbi G1 cyclin turnover and nutrient uptake are controlled by a common pathway in yeast
    Y Barral
    , Centre d Etudes de Saclay, Gif sur Yvette, France
    Genes Dev 9:399-409. 1995
    ..of this transition step in yeast is the CDC28 kinase together with its short-lived regulatory subunits called G1-cyclins or CLN proteins...
  92. pmc A pathway in quiescent cells that controls p27Kip1 stability, subcellular localization, and tumor suppression
    Arnaud Besson
    Howard Hughes Medical Institute, Division of Basic Sciences, Seattle, Washington 98109, USA
    Genes Dev 20:47-64. 2006 which Ser10 is mutated to Ala; and p27(CK-), in which point mutations abrogate the ability of p27 to bind cyclins and CDKs...
  93. 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...
  94. pmc Control of transcriptional elongation and cotranscriptional histone modification by the yeast BUR kinase substrate Spt5
    Karen Zhou
    Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto, ON, Canada M5S 3E1
    Proc Natl Acad Sci U S A 106:6956-61. 2009
  95. pmc A complex gene regulatory mechanism that operates at the nexus of multiple RNA processing decisions
    David S McPheeters
    Center for RNA Molecular Biology and Department of Molecular Biology and Microbiology, Case Western Reserve University, School of Medicine, 10900 Euclid Avenue, Cleveland, Ohio 44106 4960, USA
    Nat Struct Mol Biol 16:255-64. 2009
    ..This highly integrated regulatory strategy may ensure a rapid response to adverse conditions, thereby guaranteeing survival...
  96. pmc Phosphorylation of the Pol II CTD by KIN28 enhances BUR1/BUR2 recruitment and Ser2 CTD phosphorylation near promoters
    Hongfang Qiu
    Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA
    Mol Cell 33:752-62. 2009
    ..By contrast, CTK1 is responsible for the bulk of Ser2P in total Pol II and at promoter-distal sites. In addition to phosphorylating Ser2 near promoters, BUR1/BUR2 also stimulates Ser2P formation by CTK1 during transcription elongation...
  97. pmc The yeast carboxyl-terminal repeat domain kinase CTDK-I is a divergent cyclin-cyclin-dependent kinase complex
    D E Sterner
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Cell Biol 15:5716-24. 1995
    ..These characterizations and the availability of all of the genes encoding CTDK-I and reagents derivable from them will facilitate investigations into CTD phosphorylation and its functional consequences both in vivo and in vitro...
  98. ncbi MicroRNA let-7b targets important cell cycle molecules in malignant melanoma cells and interferes with anchorage-independent growth
    Julia Schultz
    Department of Dermatology and Venereology, University of Rostock, 18055 Rostock, Germany
    Cell Res 18:549-57. 2008
    ..Overexpression of let-7b in melanoma cells in vitro downregulated the expression of cyclins D1, D3, and A, and cyclin-dependent kinase (Cdk) 4, all of which had been described to play a role in melanoma ..
  99. 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...
  100. pmc Human CUL-1 associates with the SKP1/SKP2 complex and regulates p21(CIP1/WAF1) and cyclin D proteins
    Z K Yu
    Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 95:11324-9. 1998
    ..Aberrant expression of human p19(SKP1)/p45(SKP2)/CUL-1 complex thus may contribute to tumorigenesis by regulating the protein levels of G1 cell cycle regulators...
  101. 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
    ..The CAK holoenzyme activates complexes of CDK2 and CDC2 with various cyclins and also phosphorylates CDK2, but not CDC2, in the absence of cyclin...

Research Grants74

  1. Role of the Y-Located TSPY Gene in Human Oncogenesis
    Yun Fai Chris Lau; Fiscal Year: 2013
    ..This project will shed important insights on how the Y-oncogene and X-tumor suppressor operate and how one can interfere or boost their actions respectively to treat prostate cancer. ..
  2. Angiotensin Adrenergic Interactions in the Kidney
    Roland C Blantz; Fiscal Year: 2013
    ..oxidase and HIF-1 alpha constitute the major critical hubs leading to activation of other molecules, enzymes and cyclins/CKI important to cell proliferation and potential kidney fibrosis...
  3. Translational Machinery in Stress Signaling and Tumor Suppression
    THOMAS J contact BEGLEY; Fiscal Year: 2010
    ..The long term potential of the proposed research is significant, as understanding the mechanisms by which TRM9 inhibits tumor growth may provide novel therapeutic opportunities to restore growth-restricting programs in cancer cells. ..
  4. Prostate cancer chemoprevention by penta-galloyl-glucose
    Junxuan Lu; Fiscal Year: 2013
    ..These multiple targeting activities plus published work supporting anti- angiogenesis activity provide strong rationale for testing the efficacy of PGG for prostate cancer chemoprevention. ..
  5. Role of JAK2-PAK1 interaction in prolactin-dependent signaling
    Maria Diakonova; Fiscal Year: 2013
    ..Understanding how these proteins work together will help to design new therapeutic approaches and possibly drugs for treatment of different human diseases and breast cancer. ..
  6. Tat and CDK9 on gene expression alterations coupled to HIV-1 Associated Dementia
    Xavier Grana; Fiscal Year: 2010
    ..CDK9 in association with T-type cyclins forms Positive Transcription Elongation Factors (P-TEFb) thought to be required for the expression of cellular ..
  7. Iron-Induced Changes in Liver That Predispose to Malignancy
    Harriet C Isom; Fiscal Year: 2010
  8. Cell Cycle Regulation and Adult T Cell Leukemia
    Chou Zen Giam; Fiscal Year: 2013
    ..The study will provide molecular insights that can lead to the development of treatment strategies for human cancer ..
  9. Genistein and Prostate Cancer
    Rajvir Dahiya; Fiscal Year: 2010
    ELIZABETH ANN LEIBOLD; Fiscal Year: 2013
    ..Increased knowledge of the mechanism by which IRP2 regulates iron balance and cell proliferation is important for developing therapeutics that can be used to target cancer cells and treat iron disorders. ..
  11. Deregulated lipid metabolism in stroke
    Robert J Dempsey; Fiscal Year: 2013
    ..This proposal explores the therapeutic potential of D609 and how it affects lipid second messenger ceramide that regulates the cell cycle both in vitro and in vivo stroke models. ..
  12. Novel CTD inhibitors with synthetic lethality to oncogenic Ras for cancer therapy
    Bingliang Fang; Fiscal Year: 2013
    ..The goal of this proposal is to perform pre-clinical studies on their antitumor activities in lung cancer cells in vitro and in vivo that are required for future clinical trials. ..
  13. Integrating stress MAP kinase signaling with DNA replication origin licensing
    Jeanette Gowen Cook; Fiscal Year: 2013
    Juanita L Merchant; Fiscal Year: 2013
    ..Collectively, these studies will establish a link between ZBP-89 and pATMS1981, in the biosynthesis and function of 5HT in response to luminal butyrate. ..
  15. Beta-cell Proliferation
    Fredric E Wondisford; Fiscal Year: 2013
    ..These studies of in vivo mechanisms of [unreadable]-cell proliferation may provide therapeutic approaches for diabetes mellitus in humans. ..
  16. Link of beta cell proliferation and type 2 diabetes to epigenetic regulation
    Xianxin Hua; Fiscal Year: 2013
    ..These studies will likely pave the way to develop the next generation of new drugs to treat this widespread disease. ..
  17. Functional study of C53 protein as a novel regulator of checkpoint kinases
    Honglin Li; Fiscal Year: 2012
    ..It will lay a foundation for further exploitation of this novel protein as a potential therapeutic target in fighting diseases such as cancer. ..
  18. NADPH oxidase-associated transition from Barrett's esophagus to adenocarcinoma
    Weibiao Cao; Fiscal Year: 2013
    ..In addition, NOX5-S may be a potential biomarker for early detection of esophageal dysplasia. Our model may also be applicable to other inflammation-associated cancers. ..
    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. ..
  20. Mechanisms in transcriptional regulation during cardiac hypertrophy
    Maha Abdellatif; Fiscal Year: 2013
    ..2) Determine the role of TFIIB in gene transcription and the development of cardiac hypertrophy. 3) Determine the role of Cdk9 in gene transcription and the development of cardiac hypertrophy. ..
  21. ECM compliance and cell cycle control
    RICHARD ASSOIAN; Fiscal Year: 2012
  22. mTORC1-dependent regulation of the CycC/CDK8 complex
    Jeffrey E Pessin; Fiscal Year: 2013
  23. Organismal Radioprotection Through Pharmacological Quiescence
    JOHN S CHANT; Fiscal Year: 2010
    ..G-Zero Therapeutics is developing drugs which can be stockpiled and easily administered following such an attack to protect the bone marrow from the damaging effects of radiation. ..
  24. Regulation of HIV-1 by Rad51 in CNS cells
    Kamel Khalili; Fiscal Year: 2013
    ..The identification of novel host-viral interaction pathways can provide important information regarding the pathogenesis of AIDS/CNS disease and promote the development of more effective therapeutic strategies. ..
  25. Prevention of acute GvHD by inhibition of cdk2
    Vassiliki A Boussiotis; Fiscal Year: 2012
    ..If such approach is successful, it will have significant clinical implications because more patients will benefit from allogeneic HSCT and achieve cure without the detrimental major side effect of GvHD. ..
  26. Analysis of FIP200 in signal transduction
    Jun Lin Guan; Fiscal Year: 2012
  27. Primate Fetal Adrenal Development: Impact on Physiological Processes After Birth
    Eugene D Albrecht; Fiscal Year: 2013
    ..represses expression/interaction of ACTHR and MRAP and consequently expression of: (a) IGF-II/IGFR and the cyclins required for growth of and (b) adenylate cyclase and the low density lipoprotein (LDL)R and enzymes required for ..
  28. Cyclin-Dependent Kinase Inhibition During S Phase
    Geoffrey I Shapiro; Fiscal Year: 2013
    ..abstract_text> ..
    DEBRA LYNN LASKIN; Fiscal Year: 2012
  30. Link of beta cell proliferation and type 2 diabetes to epigenetic regulation.
    Xianxin Hua; Fiscal Year: 2010
    ..The proposed studies may pave the way to developing novel and menin pathway-based strategies to treat T2D. ..
  31. Ecd as a regulator of cell cycle and breast oncogenesis
    Vimla Band; Fiscal Year: 2013
    Sally A Camper; Fiscal Year: 2013
    ..Addressing each of these hypotheses will lead to better molecular diagnoses and provide fundamental information on pituitary precursor cell generation and proliferation. ! ..
    Lorraine J Gudas; Fiscal Year: 2013
    ..Many cancer chemoprevention trials in humans have not been successful, pointing to the need to carry out more fundamental studies and to test the idea that combination therapy may be essential for successful chemoprevention. ..
  34. 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. ..
  35. IKKbeta:Bi-Functional Regulator of Hepatocyte Proliferation
    Hyam L Leffert; Fiscal Year: 2010
    ..Attenuated co-regulated expression of hepatocyte IKK[unreadable] and JNK2 may both facilitate hepatocyte proliferation and increase the susceptibility of hepatocytes to carcinogenesis. ..
  36. Generating Blood-based Diagnosis for Alzheimer Disease
    Eugenia Wang; Fiscal Year: 2012
    ..being the first such AD diagnostic, indicating not only disease presence, but also its progress (and even drug efficacy monitoring), a huge strate- gic gain for the victims of this costly disease, and our society at large! ..
  37. Heat shock protein 90 antagonist-based therapy of mantle cell lymphoma
    Kapil Bhalla; Fiscal Year: 2012
    ..This strategy involves combinations of treatments with heat shock protein 90 and proteosome inhibitors designed to target protein folding and degradation in MCL cells. ..
    CAROL ANN LANGE; Fiscal Year: 2010
    ..This work will aid our understanding of steroid hormone action, and help to identify and implicate new therapeutic targets for breast cancer prevention and treatment. ..
  39. USC Research Center for Liver Disease
    Neil Kaplowitz; Fiscal Year: 2013
  40. HTLV-I Tax activates the anaphase promoting complex
    Chou Zen Giam; Fiscal Year: 2013
    ..The study will provide molecular insights that can lead to the development of treatment strategies for human cancer. ..
  41. Diet and Alcohol Induced Epigenetic Changes in Oral Cavity Carcinogenesis Model
    Lorraine J Gudas; Fiscal Year: 2013
    Terry L Orr-Weaver; Fiscal Year: 2013
    ..Additional targets of PNG and interacting proteins will be isolated. ..
  43. Dietary Regulation of Pancreatic Digestive Enzymes
    John A Williams; Fiscal Year: 2013
    ..Knowledge from this project should allow designing approaches to assist the human pancreas to regenerate and ensure an adequate supply of pancreatic digestive enzymes. ..
  44. Thyroid hormone-dependent DNA methylation in the developing brain
    Yasuhiro Kyono; Fiscal Year: 2012
    ..Such understanding can contribute to the prevention, diagnosis and treatment of human neurological conditions such as mental retardation, autism spectrum disorder and schizophrenia. ..
  45. Mdig gene and histone demethylation in lung cancer
    Fei Chen; Fiscal Year: 2013
    ..lysine 9 on histone H3;(2) determine whether the expression of the cell cycle-regulated genes, such as cyclins, Cdc25s and checkpoint proteins, is regulated by the methylation regulation of mdig;and (3) study the tumorigenic ..
  46. Signaling of Integrin Alpha 7
    Jianhua Luo; Fiscal Year: 2009
    ..abstract_text> ..
  47. Molecular and Cellular Regulation of Mammalian Renal Medulla Development
    Jing Yu; Fiscal Year: 2013
  48. TGF-Beta in Intimal Hyperplasia after Vascular Bypass
    K Craig Kent; Fiscal Year: 2013
    ..The long-term goal is to develop specific therapies that prevent or halt the progression of arterial restenosis, thus reducing morbidity and mortality for thousands of individuals each year. ..
  49. Cyclin E Regulation in Normal and Neoplastic Hematopoiesis
    ALEXANDER C MINELLA; Fiscal Year: 2013
    ..The investigators now propose to study how high cyclin E levels cause these blood cell defects and contribute to bone marrow failure and cancers. ..
  50. Signaling of Integrin Alpha 7
    Jianhua Luo; Fiscal Year: 2013
  51. Molecular mechanisms of C/EBP alpha mediated growth arrest
    Nikolai A Timchenko; Fiscal Year: 2013
    ..The elucidation of these mechanisms will provide basement for the generation of therapeutic approaches to prevent tumors. ..
  52. Glypican-1 in gliomagenesis
    Andreas Friedl; Fiscal Year: 2013
    ..The GPC1 signaling pathway may offer opportunities for therapeutic intervention by targeting either GPC1 itself or downstream mediators. ..
  53. Cell Cycle Pathways and Spinal Cord Injury
    ALAN IRA FADEN; Fiscal Year: 2011
    ..therapeutically relevant, delayed systemic administration of Flavopiridol improves post-traumatic function and histological outcome. ..
  54. Novel mechanisms of immune activation following allogeneic, hematopoietic stem ce
    JOHN JAMES LETTERIO; Fiscal Year: 2013
  55. Regulation and Role of Ornithine Decarboxylase in Cell Proliferation and Cancer
    John L Cleveland; Fiscal Year: 2013
    ..abstract_text> ..
  56. Stat3 in Epitherlial Carcinogenesis
    John DiGiovanni; Fiscal Year: 2012
    ..Furthermore, the proposed studies will provide additional evidence that keratinocyte stem cells, particularly those found in the bulge region of hair follicles, may be the primary target cells for tumor development in mouse skin. ..
  57. Role of Kruppel-Like Factor 4 in Wnt and Notch Signaling in the Intestinal Tract
    Amr Ghaleb; Fiscal Year: 2010
    ..The further elucidation of the functions of KLF4 in CRC may lead to new insights into the mechanism of intestinal tumorigenesis. ..
  58. Roles of Epstein-Barr virus nuclear antigens 2 and LP in B cell proliferation
    Elliott D Kieff; Fiscal Year: 2013
  59. Control of the Erythroid Terminal Differentiation Decision
    Arthur I Skoultchi; Fiscal Year: 2013
    ..The successful completion of this work will enable the development of new approaches to managing defects in red blood cell production that occur in chronic and acute anemia due to a variety of causes. ..
  60. Chimaerins-receptors for diacylgly and phorbal esters
    ..This proposal will investigate the relevance of 2-chimaerin in breast cancer progression as well as key regulatory mechanisms that control its activation and function. ..
    Alexander W Clowes; Fiscal Year: 2013
  62. Control of cell number in developing retina
    Duojia Pan; Fiscal Year: 2013
    ..Such insights may facilitate the therapeutic interventions of relevant human diseases, including diseases of the retina. ..
    Stuart Ravnik; Fiscal Year: 2002
    ..To date, there is little data on the identity and/or function of the cyclins and Cdks during meiosis, especially with regard to the meiotic divisions that take place during spermatogenesis...
  64. Effect of Cdk inhibitor on HIV-1 replication
    Fatah Kashanchi; Fiscal Year: 2007
    ..Therefore, the current proposal is aimed at determining whether drugs such as ATP analogs are a viable option in treating HIV-1 infected cells both in vitro and in vivo. [unreadable] [unreadable] [unreadable]..
  65. Mouse Models of ErbB-2 and Cyclin D1 in Prostate Cancer
    Christopher Albanese; Fiscal Year: 2002
    ..abstract_text> ..
  66. Mechanistic regulation of tumor specific forms of cyclin E in breast cancer
    NIKKI A DELK; Fiscal Year: 2010
    ..Elucidation of the signaling molecules or pathways that regulate cyclin E stability and function can lead to rational approaches to target aberrant cyclin E expression in tumors. ..
    Jeffrey Pollard; Fiscal Year: 2005
    ..In tissue culture cells the cell cycle is regulated by the orderly activation of cyclins and their dependent kinases (Cdk)...
    Philip Hinds; Fiscal Year: 2006
    Raymond Deshaies; Fiscal Year: 2000
    ..Among these genes are G1 cyclins and a Cdk required for progression from G1 to S phase. Dr...
    MARC HERSHENSON; Fiscal Year: 2002 indicating that the 21 kD GTPase Rac1 is sufficient to induce transcriptional activation of two G1 cyclins, cyclin D1 and cyclin A, in bovine tracheal myocytes...
  71. The Role of Cell Size and G1-phase Cdks in Cell Growth Control
    Brandt L Schneider; Fiscal Year: 2010
    ..predominately by growth factors and mitogens which promote proliferation by inducing the expression of G1-phase cyclins. However, the mechanisms that control the timing, expression levels, and activity of G1-phase cyclins are still ..
    RICHARD ASSOIAN; Fiscal Year: 2007
    ..abstract_text> ..
    Johannes Rudolph; Fiscal Year: 2004
    ..abstract): The eukaryotic cell cycle is tightly regulated by the action of the cyclin-dependent kinases (Cdk/cyclins)...
  74. Cyclin A1 as a Target in AML and Other Cancers
    DEBRA WOLGEMUTH; Fiscal Year: 2003