Cdk6

Summary

Gene Symbol: Cdk6
Description: cyclin-dependent kinase 6
Alias: AI504062, Crk2, cyclin-dependent kinase 6, CR2 protein kinase, cell division protein kinase 6, serine/threonine-protein kinase PLSTIRE
Species: mouse

Top Publications

  1. ncbi Activation of a Dab1/CrkL/C3G/Rap1 pathway in Reelin-stimulated neurons
    Bryan A Ballif
    Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA
    Curr Biol 14:606-10. 2004
  2. pmc A requirement for cyclin-dependent kinase 6 in thymocyte development and tumorigenesis
    Miaofen G Hu
    Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111, USA
    Cancer Res 69:810-8. 2009
  3. doi c-JUN promotes BCR-ABL-induced lymphoid leukemia by inhibiting methylation of the 5' region of Cdk6
    Karoline Kollmann
    Institute of Pharmacology, Center of Biomolecular Medicine and Pharmacology, Medical University of Vienna, Vienna, Austria
    Blood 117:4065-75. 2011
  4. ncbi Cyclin D1-dependent kinase activity in murine development and mammary tumorigenesis
    Mark W Landis
    Molecular Oncology Research Institute and Department of Radiation Oncology, Tufts New England Medical Center, 750 Washington Street 5609, Boston, Massachusetts 02111, USA
    Cancer Cell 9:13-22. 2006
  5. pmc Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemia
    Catherine M Sawai
    Department of Pathology and Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA
    Cancer Cell 22:452-65. 2012
  6. ncbi Cell cycle progression without cyclin D-CDK4 and cyclin D-CDK6 complexes
    Katarzyna Kozar
    Department of Cancer Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
    Cell Cycle 4:388-91. 2005
  7. ncbi Mammalian cells cycle without the D-type cyclin-dependent kinases Cdk4 and Cdk6
    Marcos Malumbres
    Molecular Oncology Program, Centro Nacional de Investigaciones Oncologicas CNIO, E 28029 Madrid, Spain
    Cell 118:493-504. 2004
  8. ncbi Mouse development and cell proliferation in the absence of D-cyclins
    Katarzyna Kozar
    Department of Cancer Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cell 118:477-91. 2004
  9. ncbi Cdk6-cyclin D3 activity in murine ES cells is resistant to inhibition by p16(INK4a)
    Renate Faast
    Department of Molecular Biosciences, BresaGen Cell Therapy Program, Center for Molecular Genetics of Development, University of Adelaide, Adelaide, South Australia, Australia
    Oncogene 23:491-502. 2004
  10. ncbi The Rb-CDK4/6 signaling pathway is critical in neural precursor cell cycle regulation
    K L Ferguson
    Neuroscience Research Institute, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada
    J Biol Chem 275:33593-600. 2000

Research Grants

  1. INTEGRATION OF STRESS AND MITOGEN SIGNALING
    Jonathan Cooper; Fiscal Year: 2001
  2. Role of the JIP-1-p190RhoGEF Complex In Neuron Function
    WILLIAM ARTHUR; Fiscal Year: 2004

Scientific Experts

  • Henrique Veiga-Fernandes
  • Marcos Malumbres
  • Suzana Atanasoski
  • Vitezslav Bryja
  • Jonathan A Cooper
  • Karoline Kollmann
  • WILLIAM ARTHUR
  • David Santamaria
  • Philip W Hinds
  • Piotr Sicinski
  • Miaofen G Hu
  • Mariano Barbacid
  • Veronika Sexl
  • Mark W Landis
  • Pierre Dubus
  • Katarzyna Kozar
  • Okkyung Rho
  • N Jena
  • Sidinh Luc
  • Martha J Grossel
  • Pavan Kumar P
  • Pirita Pekkonen
  • Esther Rodríguez-Díez
  • K Ito
  • Lionel Nobs
  • Emma Juuri
  • Muhammad S Hussain
  • Haidan Liu
  • Da Mi
  • Peter Slomiany
  • Javier Lopez-Rios
  • Wolfgang Warsch
  • Catherine M Sawai
  • Akihiko Ishimura
  • Ruth Scheicher
  • Sabine Zochbauer-Muller
  • Christine Schneckenleithner
  • Taras Kreslavsky
  • Gerwin Heller
  • Toru Ogasawara
  • Xian Wang
  • El Kahina Meziane
  • Elizabeth J Hennessy
  • Mayumi Mori
  • Pierre Beukelaers
  • Hiroto Okayama
  • Karine Michaud
  • Marei Dose
  • Amit Deshpande
  • Hanneke L D M Willemen
  • Elisabeth A Hinds
  • Dayana B Rivadeneira
  • Changchuin Mao
  • Guo fu Hu
  • Marta Puyol
  • Fotini Gounari
  • Kevin S Choe
  • W Ruprecht Wiedemeyer
  • Sebastian Fuchs
  • Zhengmin Yang
  • Amel Chebel
  • Dawn M Kohrt
  • Hiroaki Kiyokawa
  • T Fujimoto
  • Selina Chen-Kiang
  • Arthur I Skoultchi
  • Lynda Chin
  • Cyril Berthet
  • Yan Geng
  • M Barbacid
  • Toru Moro
  • Edwina McGlinn
  • Jason W Upton
  • Hiroshi Kawaguchi
  • Kazuto Hoshi
  • Kozo Nakamura
  • Bryan A Ballif
  • Renate Faast
  • J Kohoutek
  • Shigeki Jinno
  • J Sheng
  • A Pathak
  • Jian Xu
  • Dan Li
  • A Deshpande
  • Shahan Mamoor
  • W Zhou
  • Ece Somuncular
  • M G Hu
  • C Luo

Detail Information

Publications77

  1. ncbi Activation of a Dab1/CrkL/C3G/Rap1 pathway in Reelin-stimulated neurons
    Bryan A Ballif
    Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA
    Curr Biol 14:606-10. 2004
    ..C3G and Rap1 regulate adhesion of fibroblasts and other cell types. Regulation of Crk/CrkL, C3G, and Rap1 by Reelin may be involved in coordinating neuron migrations during brain development...
  2. pmc A requirement for cyclin-dependent kinase 6 in thymocyte development and tumorigenesis
    Miaofen G Hu
    Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111, USA
    Cancer Res 69:810-8. 2009
    Cyclin-dependent kinase 6 (CDK6) promotes cell cycle progression and is overexpressed in human lymphoid malignancies. To determine the role of CDK6 in development and tumorigenesis, we generated and analyzed knockout mice...
  3. doi c-JUN promotes BCR-ABL-induced lymphoid leukemia by inhibiting methylation of the 5' region of Cdk6
    Karoline Kollmann
    Institute of Pharmacology, Center of Biomolecular Medicine and Pharmacology, Medical University of Vienna, Vienna, Austria
    Blood 117:4065-75. 2011
    ..The decreased proliferation of c-Jun(Δ/Δ) cells is associated with the loss of cyclin-dependent kinase 6 (CDK6) expression...
  4. ncbi Cyclin D1-dependent kinase activity in murine development and mammary tumorigenesis
    Mark W Landis
    Molecular Oncology Research Institute and Department of Radiation Oncology, Tufts New England Medical Center, 750 Washington Street 5609, Boston, Massachusetts 02111, USA
    Cancer Cell 9:13-22. 2006
    Cyclin D1 is a multifunctional protein that activates CDK4 and CDK6, titrates Cip/Kip CDK inhibitors to increase CDK2 activity, and modulates the function of certain transcription factors...
  5. pmc Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemia
    Catherine M Sawai
    Department of Pathology and Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA
    Cancer Cell 22:452-65. 2012
    ..These studies identify unique functions for cyclin D3:CDK4/6 complexes and suggest potential therapeutic protocols for this devastating blood tumor...
  6. ncbi Cell cycle progression without cyclin D-CDK4 and cyclin D-CDK6 complexes
    Katarzyna Kozar
    Department of Cancer Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
    Cell Cycle 4:388-91. 2005
    D-type cyclins (cyclin D1, D2 and D3) and their associated cyclin-dependent kinases CDK4 and CDK6 were thought to represent important, perhaps essential components of the core cell cycle apparatus...
  7. ncbi Mammalian cells cycle without the D-type cyclin-dependent kinases Cdk4 and Cdk6
    Marcos Malumbres
    Molecular Oncology Program, Centro Nacional de Investigaciones Oncologicas CNIO, E 28029 Madrid, Spain
    Cell 118:493-504. 2004
    Cdk4 and Cdk6 are thought to be essential for initiation of the cell cycle in response to mitogenic stimuli...
  8. ncbi Mouse development and cell proliferation in the absence of D-cyclins
    Katarzyna Kozar
    Department of Cancer Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cell 118:477-91. 2004
    ..Lastly, we found that cells lacking D-cyclins display reduced susceptibility to the oncogenic transformation. Our results reveal the presence of alternative mechanisms that allow cell cycle progression in a cyclin D-independent fashion...
  9. ncbi Cdk6-cyclin D3 activity in murine ES cells is resistant to inhibition by p16(INK4a)
    Renate Faast
    Department of Molecular Biosciences, BresaGen Cell Therapy Program, Center for Molecular Genetics of Development, University of Adelaide, Adelaide, South Australia, Australia
    Oncogene 23:491-502. 2004
    ..b>Cdk6 is the major catalytic partner for cyclin D3 in ES cells and exhibits robust pRb kinase activity that is ..
  10. ncbi The Rb-CDK4/6 signaling pathway is critical in neural precursor cell cycle regulation
    K L Ferguson
    Neuroscience Research Institute, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada
    J Biol Chem 275:33593-600. 2000
    ..Furthermore, our data underscore the importance of the Rb regulatory pathway in neuronal development and cell cycle regulation, independent of CKI sequestration...
  11. ncbi Expression of cyclin-dependent kinase 6, but not cyclin-dependent kinase 4, alters morphology of cultured mouse astrocytes
    Karen K Ericson
    Department of Biology, Connecticut College, New London, CT 06320, USA
    Mol Cancer Res 1:654-64. 2003
    ..The D-cyclin-associated kinases, cyclin-dependent kinase (cdk) 4 and cdk6, are important regulators of the G(1)-S phase transition and are elevated in several types of cancers, including ..
  12. pmc Bcl11a Deficiency Leads to Hematopoietic Stem Cell Defects with an Aging-like Phenotype
    Sidinh Luc
    Division of Hematology Oncology, Boston Children s Hospital, Boston, MA 02115, USA Department of Pediatric Oncology, Dana Farber Cancer Institute and Harvard Stem Cell Institute, Boston, MA 02115, USA Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
    Cell Rep 16:3181-94. 2016
    ..We find that downregulation of cyclin-dependent kinase 6 (Cdk6), and the ensuing cell-cycle delay, correlate with HSC dysfunction...
  13. doi Knockdown of Fbxo7 reveals its regulatory role in proliferation and differentiation of haematopoietic precursor cells
    El Kahina Meziane
    Division of Cellular and Genetic Pathology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB21QP, UK
    J Cell Sci 124:2175-86. 2011
    ..Fbxo7 directly binds p27 and Cdk6, enhances the level of cyclin D-Cdk6 complexes, and its overexpression causes Cdk6-dependent transformation of ..
  14. doi Overexpression of Cdk6 and Ccnd1 in chondrocytes inhibited chondrocyte maturation and caused p53-dependent apoptosis without enhancing proliferation
    K Ito
    1 Department of Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan 2 Department of Molecular Bone Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan 3 Nagasaki University Research Centre for Genomic Instability and Carcinogenesis NRGIC, Nagasaki, Japan
    Oncogene 33:1862-71. 2014
    ..However, we previously showed that overexpression of cyclin-dependent kinase (Cdk6) blocks chondrocyte differentiation without affecting cell-cycle progression in vitro...
  15. doi Establishment of crown-root domain borders in mouse incisor
    Emma Juuri
    Institute of Biotechnology, Developmental Biology Program, University of Helsinki, 00014 Helsinki, Finland
    Gene Expr Patterns 13:255-64. 2013
    ..The use of different mechanisms to establish domain borders gives indications of the incisor functional asymmetry. ..
  16. doi Cyclin D1 is required for proliferation of Olig2-expressing progenitor cells in the injured cerebral cortex
    Lionel Nobs
    Institute of Physiology, Department of Biomedicine, University of Basel, Basel, Switzerland
    Glia 61:1443-55. 2013
    ..Further, we show that cyclin-dependent kinase (cdk) 4, but not cdk6 or cdk2, is essential for driving cell division of Olig2-expressing cells in our injury model...
  17. doi CDK6 associates with the centrosome during mitosis and is mutated in a large Pakistani family with primary microcephaly
    Muhammad S Hussain
    Cologne Center for Genomics CCG
    Hum Mol Genet 22:5199-214. 2013
    ..589G>A in CDK6, which encodes cyclin-dependent kinase 6...
  18. pmc CDK6-mediated repression of CD25 is required for induction and maintenance of Notch1-induced T-cell acute lymphoblastic leukemia
    N Jena
    Department of Medicine, Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA, USA
    Leukemia 30:1033-43. 2016
    ..We showed previously that cyclin-dependent kinase 6 (CDK6) is required for thymic lymphoblastic lymphoma induced by activated AKT...
  19. pmc Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6
    H Hirai
    Department of Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Mol Cell Biol 15:2672-81. 1995
    ..members of the mouse INK4 gene family, p19 and p18, that specifically inhibit the kinase activities of CDK4 and CDK6, but do not affect those of cyclin E-CDK2, cyclin A-CDK2, or cyclin B-CDC2, were isolated...
  20. doi Overexpression of PRAS40(T246A) in the Proliferative Compartment Suppresses mTORC1 Signaling, Keratinocyte Migration, and Skin Tumor Development
    Okkyung Rho
    Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, Texas, USA
    J Invest Dermatol 136:2070-9. 2016
    ..Collectively, the current data using this unique mouse model provide further evidence that mTORC1 signaling in keratinocytes regulates key events in keratinocyte function and epithelial cancer development. ..
  21. pmc KSHV viral cyclin interferes with T-cell development and induces lymphoma through Cdk6 and Notch activation in vivo
    Pirita Pekkonen
    a Institute of Biotechnology University of Helsinki Helsinki, Finland
    Cell Cycle 13:3670-84. 2014
    Kaposi's sarcoma herpesvirus (KSHV)-encoded v-cyclin, a homolog of cellular cyclin D2, activates cellular CDK6, promotes G1-S transition of the cell cycle, induces DNA damage, apoptosis, autophagy and is reported to have oncogenic ..
  22. doi Cdk4 and Cdk6 cooperate in counteracting the INK4 family of inhibitors during murine leukemogenesis
    Esther Rodríguez-Díez
    Cell Division and Cancer Group, Spanish National Cancer Research Centre CNIO, Madrid, Spain
    Blood 124:2380-90. 2014
    Cdk4 and Cdk6 are related protein kinases that bind d-type cyclins and regulate cell-cycle progression. Cdk4/6 inhibitors are currently being used in advanced clinical trials and show great promise against many types of tumors...
  23. pmc Coordinated control of senescence by lncRNA and a novel T-box3 co-repressor complex
    Pavan Kumar P
    Weis Center for Research, Geisinger Clinic, Danville, United States
    elife 3:. 2014
    ..Our elucidation of CAPERα and UCA1 functions in vivo provides new insights into senescence induction, and the oncogenic and developmental properties of TBX3. ..
  24. pmc A kinase-independent function of CDK6 links the cell cycle to tumor angiogenesis
    Karoline Kollmann
    Institute of Pharmacology and Toxicology, University of Veterinary Medicine Vienna, 1210 Vienna, Austria
    Cancer Cell 24:167-81. 2013
    In contrast to its close homolog CDK4, the cell cycle kinase CDK6 is expressed at high levels in lymphoid malignancies...
  25. pmc A chrysin derivative suppresses skin cancer growth by inhibiting cyclin-dependent kinases
    Haidan Liu
    World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Ochang, Cheongwon 363 883, Republic of Korea
    J Biol Chem 288:25924-37. 2013
    ..This study provides new insights for creating a general pharmacophore model to design and develop novel ATP-noncompetitive agents with chemopreventive or chemotherapeutic potency. ..
  26. pmc Death effector domain-containing protein (DEDD) is required for uterine decidualization during early pregnancy in mice
    Mayumi Mori
    Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo ku, Tokyo, Japan
    J Clin Invest 121:318-27. 2011
    ..These results indicate that DEDD is indispensable for the establishment of an adequate uterine environment to support early pregnancy in mice...
  27. doi Postnatal Schwann cell proliferation but not myelination is strictly and uniquely dependent on cyclin-dependent kinase 4 (cdk4)
    Suzana Atanasoski
    Institute of Cell Biology, ETH Zurich, Zurich, Switzerland
    Mol Cell Neurosci 37:519-27. 2008
    ..In contrast, ablation of cdk2 and cdk6 had no significant influence on postnatal Schwann cell proliferation...
  28. pmc Distinct and nonoverlapping roles for pRB and cyclin D:cyclin-dependent kinases 4/6 activity in melanocyte survival
    Benjamin D Yu
    Howard Hughes Medical Institute, University of California at San Diego School of Medicine, La Jolla, CA 92093 0686, USA
    Proc Natl Acad Sci U S A 100:14881-6. 2003
    ..These findings suggest that deregulated cyclin D:cdk4/6 complexes and pRB perform nonoverlapping functions in vivo and provide a cellular mechanism that accounts for the low incidence of RB inactivation in cancers such as melanoma...
  29. pmc Increased expression of cyclin D2 during multiple states of growth arrest in primary and established cells
    M Meyyappan
    Departments of Medical Science, Southern Alberta Cancer Research Center, Calgary, Alberta, Canada T2N 4N1
    Mol Cell Biol 18:3163-72. 1998
    ..Cyclin D2 was also found to be associated with the cyclin-dependent kinases CDK2 and CDK4 but not CDK6 during growth arrest...
  30. ncbi Cutting edge: differential signaling requirements for activation of assembled cyclin D3-cdk4 complexes in B-1 and B-2 lymphocyte subsets
    D A Tanguay
    Department of Biology, Boston College, Chestnut Hill, MA 02467, USA
    J Immunol 166:4273-7. 2001
    ..These results reveal a novel regulatory step that controls activation of cyclin D3-cdk4 complexes whose function segregates differentially in B cell subsets...
  31. doi Jmjd5, an H3K36me2 histone demethylase, modulates embryonic cell proliferation through the regulation of Cdkn1a expression
    Akihiko Ishimura
    Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kakuma machi, Kanazawa, Ishikawa 920 1192, Japan
    Development 139:749-59. 2012
    ..Taken together, these results suggest that Jmjd5 physiologically moderates embryonic cell proliferation through the epigenetic control of Cdkn1a expression...
  32. pmc Pharmacologic inhibition of cyclin-dependent kinases 4 and 6 arrests the growth of glioblastoma multiforme intracranial xenografts
    Karine Michaud
    Department of Neurological Surgery, Helen Diller Comprehensive Cancer Center, University of California San Francisco, California 94143 0520, USA
    Cancer Res 70:3228-38. 2010
    ..In total, our results support clinical trial evaluation of PD-0332991 against newly diagnosed as well as recurrent GBM, and indicate that Rb status is the primary determinant of potential benefit from this therapy...
  33. pmc GLI3 constrains digit number by controlling both progenitor proliferation and BMP-dependent exit to chondrogenesis
    Javier Lopez-Rios
    Developmental Genetics, Department of Biomedicine, University of Basel, 4058 Basel, Switzerland
    Dev Cell 22:837-48. 2012
    ..revealed that GLI3 directly restricts the expression of regulators of the G(1)-S cell-cycle transition such as Cdk6 and constrains S phase entry of digit progenitors in the anterior hand plate...
  34. ncbi Characterization of murine gammaherpesvirus 68 v-cyclin interactions with cellular cdks
    Jason W Upton
    Center for Emerging Infectious Diseases, Yerkes National Primate Research Center, Emory University School of Medicine, NE Atlanta, GA 30329, USA
    Virology 341:271-83. 2005
    ..the gammaHV68 v-cyclin preferentially interacts with cdk2 and cdc2 but does not interact with either cdk4 or cdk6. Mutation of conserved residues, predicted to be involved in cdk binding based on the gammaHV68 v-cyclin:cdk2 ..
  35. ncbi Formation of p27-CDK complexes during the human mitotic cell cycle
    T J Soos
    Program in Molecular Biology, Memorial Sloan Kettering Cancer Research Center, New York, New York 10021, USA
    Cell Growth Differ 7:135-46. 1996
    ..cells, p27 associates with and inhibits cyclin/cycin-dependent kinase (CDK) holoenzymes containing either CDK4, CDK6, or CDK2...
  36. pmc β-Selection-induced proliferation is required for αβ T cell differentiation
    Taras Kreslavsky
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Immunity 37:840-53. 2012
    ..Consistently, pharmacological inhibition of the cell cycle machinery also blocked differentiation in vivo. Thus the proliferation step is strictly required prior to differentiation of immature thymocytes...
  37. pmc Pax6 exerts regional control of cortical progenitor proliferation via direct repression of Cdk6 and hypophosphorylation of pRb
    Da Mi
    Centre for Integrative Physiology, University of Edinburgh, Edinburgh EH8 9XD, UK
    Neuron 78:269-84. 2013
    ..Biochemical assays indicated that Pax6 directly represses Cdk6 expression...
  38. ncbi PKD1 induces p21(waf1) and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2
    Anil Kumar Bhunia
    Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Cell 109:157-68. 2002
    ..These results suggest that one function of the polycystin-1/2 complex is to regulate the JAK/STAT pathway and explain how mutations of either gene can result in dysregulated growth...
  39. pmc Toll-like receptor-4 (TLR4) down-regulates microRNA-107, increasing macrophage adhesion via cyclin-dependent kinase 6
    Elizabeth J Hennessy
    School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland
    J Biol Chem 286:25531-9. 2011
    ..We have found that the putative miR-107 target cyclin-dependent kinase 6 (CDK6) expression is increased by TLR4 as a result of the decrease in miR-107...
  40. pmc CDK6 kinase activity is required for thymocyte development
    Miaofen G Hu
    Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA, USA
    Blood 117:6120-31. 2011
    Cyclin-dependent kinase-6 (CDK6) is required for early thymocyte development and tumorigenesis...
  41. doi Cdk6-dependent regulation of G(1) length controls adult neurogenesis
    Pierre Beukelaers
    GIGA Neurosciences, University of Liege, Liege, Belgium
    Stem Cells 29:713-24. 2011
    ..Here, we unravel the major contribution of the G(1) regulator cyclin-dependent kinase 6 (Cdk6) to adult neurogenesis...
  42. pmc Unexpected reduction of skin tumorigenesis on expression of cyclin-dependent kinase 6 in mouse epidermis
    Xian Wang
    Department of Molecular Biomedical Sciences, Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, North Carolina, USA
    Am J Pathol 178:345-54. 2011
    ..To study the role of CDK6 in epithelial growth and tumorigenesis, we generated transgenic mice carrying the CDK6 gene under the keratin 5 ..
  43. 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
    ..to require the sequential activation of at least four different cyclin-dependent kinases, Cdk2, Cdk3, Cdk4 and Cdk6, to drive cells through interphase, as well as Cdk1 to proceed through mitosis...
  44. pmc Microglial/macrophage GRK2 determines duration of peripheral IL-1beta-induced hyperalgesia: contribution of spinal cord CX3CR1, p38 and IL-1 signaling
    Hanneke L D M Willemen
    Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands
    Pain 150:550-60. 2010
    ..We propose that chronic inflammation decreases spinal microglial/macrophage GRK2, which prevents silencing of microglia/macrophage activity and thereby contributes to prolonged hyperalgesia...
  45. doi A synthetic lethal interaction between K-Ras oncogenes and Cdk4 unveils a therapeutic strategy for non-small cell lung carcinoma
    Marta Puyol
    Molecular Oncology Programme, Centro Nacional de Investigaciones Oncologicas, E 28029 Madrid, Spain
    Cancer Cell 18:63-73. 2010
    ..Ablation of Cdk4, but not Cdk2 or Cdk6, induces an immediate senescence response only in lung cells that express an endogenous K-Ras oncogene...
  46. pmc Pattern of retinoblastoma pathway inactivation dictates response to CDK4/6 inhibition in GBM
    W Ruprecht Wiedemeyer
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 107:11501-6. 2010
    ..Here, we combined functional genetic screens and comprehensive genomic analyses to identify CDK6 as a GBM oncogene that is required for proliferation and viability in a subset of GBM cell lines and tumors...
  47. pmc Bone morphogenetic protein 2-induced osteoblast differentiation requires Smad-mediated down-regulation of Cdk6
    Toru Ogasawara
    Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, University of Tokyo, 7 3 1 Hongo, Bunkyo, Tokyo 113 0033, Japan
    Mol Cell Biol 24:6560-8. 2004
    ..Of the G(1) cell cycle factors examined, the expression of cyclin-dependent kinase 6 (Cdk6) was found to be strongly down-regulated by BMP-2/Smads signaling, mainly via transcriptional repression...
  48. pmc A family of human cdc2-related protein kinases
    M Meyerson
    Massachusetts General Hospital Cancer Center, Charlestown 02129
    EMBO J 11:2909-17. 1992
    ..The identification of a large family of cdc2-related kinases opens the possibility of combinatorial regulation of the cell cycle together with the emerging large family of cyclins...
  49. ncbi Cloning and characterization of murine p16INK4a and p15INK4b genes
    D E Quelle
    Howard Hughes Medical Institute, Memphis, Tennessee, USA
    Oncogene 11:635-45. 1995
    ..through the G1 phase of the cell cycle is regulated in part by the D-type cyclin-dependent kinases, cdk4 and cdk6. Genes encoding two specific inhibitors of these kinases, human p16(INK4a/MTS1) and p15(INK4b/MTS2), map to a ..
  50. ncbi Novel CDC2-related protein kinases produced in murine hematopoietic stem cells
    M Ershler
    W A Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow
    Gene 124:305-6. 1993
    ..In total, nine different PK-encoding sequences were obtained. At least four of them encode previously unknown PKs...
  51. ncbi Expression of INK4 inhibitors of cyclin D-dependent kinases during mouse brain development
    F Zindy
    Department of Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Cell Growth Differ 8:1139-50. 1997
    ..of mRNAs encoding two polypeptide inhibitors (p18INK4c and p19INK4d) of cyclin D-dependent kinase (CDK) 4 and CDK6 in the central nervous system. No expression of two other INK4 members, p16INK4a and p15INK4b, was observed...
  52. ncbi Control of cell cycle gene expression in bone development and during c-Fos-induced osteosarcoma formation
    A Sunters
    Department of Orthodontics, UMDS Guy s Hospital, London, United Kingdom
    Dev Genet 22:386-97. 1998
    ..Cyclin D1 expression was absent despite high levels of CDK4 and CDK6, and the CKI p27 was expressed in chondrocytes, osteoclasts, and at lower levels in osteoblasts...
  53. ncbi Human-mouse comparative mapping of the genomic region containing CDK6: localization of an evolutionary breakpoint
    J W Thomas
    Genome Technology Branch, National Human Genome Research Institute, 49 Convent Drive, Bldg 49, Room 2A08, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mamm Genome 10:764-7. 1999
  54. pmc Evidence for coordinated interaction of cyclin D3 with p21 and cdk6 in directing the development of uterine stromal cell decidualization and polyploidy during implantation
    Jian Tan
    Department of Obstetrics and Gynecology, MRRC 37 3004, Ralph L Smith Research Center, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160 7338, USA
    Mech Dev 111:99-113. 2002
    ..coordinate expression and functional association of cyclin D3 with cdk4 suggest a role for proliferation and, that of cyclin D3 with p21 and cdk6 is consistent with the development of polyploidy during stromal cell decidualization.
  55. ncbi CDK inhibitor p18(INK4c) is required for the generation of functional plasma cells
    Michelle R Tourigny
    Department of Pathology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Immunity 17:179-89. 2002
    ..link between cell cycle control and plasma cell differentiation may, at least in part, relate to p18(INK4c) inhibition of CDK6. Cell cycle arrest mediated by p18(INK4C) is therefore requisite for the generation of functional plasma cells.
  56. ncbi A Crk-II/TC10 signaling pathway is required for osmotic shock-stimulated glucose transport
    Philippe Gual
    INSERM U 568 and IFR 50, Faculte de Medecine, Avenue de Valombrose, 06107 Nice, Cedex 02, France
    J Biol Chem 277:43980-6. 2002
    ..These data provide the first evidence that activation of TC10 and remodeling of cortical actin, which could occur through the TC10 signaling, are required for osmotic shock-mediated Glut 4 translocation and glucose uptake...
  57. ncbi Overexpression of Cdk6-cyclin D3 highly sensitizes cells to physical and chemical transformation
    Qiuhong Chen
    Department of Biochemistry and Molecular Biology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    Oncogene 22:992-1001. 2003
    Virtually all mammalian cells express two seemingly redundant cyclin-D-dependent kinases (Cdk4 and Cdk6) and three partner cyclins (D1, D2 and D3) essential for the G(1)-S transition, with predominant expression of Cdk4 and D1 in ..
  58. ncbi CDK6 blocks differentiation: coupling cell proliferation to the block to differentiation in leukemic cells
    Igor Matushansky
    Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Oncogene 22:4143-9. 2003
    ..We found that CDK6 (but not CDK4) is rapidly downregulated as MEL cells are induced to re-enter erythroid differentiation and that ..
  59. ncbi Temporal distribution of CDK4, CDK6, D-type cyclins, and p27 in developing mouse oocytes
    J Kohoutek
    Laboratory of Molecular Embryology, Mendel University Brno, 613 00 Brno, Czech Republic
    Biol Reprod 70:139-45. 2004
    ..study seeks to initiate analyses of the potential oocyte-specific functions of regulators of G1/S progression-CDK4, CDK6, D-type cyclins, and p27-by first determining their expression patterns in growing and maturing mouse oocytes and ..
  60. ncbi Array comparative genome hybridization for tumor classification and gene discovery in mouse models of malignant melanoma
    Rónán C O'Hagan
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Cancer Res 63:5352-6. 2003
    ..Kannan, et al., Proc. Natl. Acad. Sci. USA, 21: 2003). These results are the first to establish the utility of array-CGH as a means of etiology-based tumor classification in genetically defined cancer-prone models...
  61. ncbi High expression of active CDK6 in the cytoplasm of CD8 memory cells favors rapid division
    Henrique Veiga-Fernandes
    Institut National de la Santé et de la Recherche Médicale U591, Institut Necker, 156 rue de Vaugirard, 75015 Paris, France
    Nat Immunol 5:31-7. 2004
    ..Naive cells are in a classical state of G0/G1 arrest, with high expression of p27Kip1 and low CDK6 and CDK2 kinase activity. In contrast, memory cells have low expression of p27Kip1 and high CDK6 kinase activity...
  62. pmc Proliferative suppression by CDK4/6 inhibition: complex function of the retinoblastoma pathway in liver tissue and hepatoma cells
    Dayana B Rivadeneira
    Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
    Gastroenterology 138:1920-30. 2010
    ..Here, we analyzed the ability of CDK4/6 inhibition to inhibit hepatocyte proliferation and the effect of RB status on this process...
  63. ncbi Inhibition of Cdk6 expression through p38 MAP kinase is involved in differentiation of mouse prechondrocyte ATDC5
    Toru Moro
    Department of Sensory and Motor System Medicine, Faculty of Medicine, University of Tokyo, Japan
    J Cell Physiol 204:927-33. 2005
    ..Among the G1 cell cycle factors examined, both protein and mRNA levels of cyclin-dependent kinase (Cdk6) were downregulated during the culture in a differentiation medium...
  64. ncbi Pax9 and Jagged1 act downstream of Gli3 in vertebrate limb development
    Edwina McGlinn
    Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia
    Mech Dev 122:1218-33. 2005
    ..Our data have also revealed that perturbation of early patterning events within the Gli3(Xt/Xt) limb culminates in a specific delay of anterior chondrogenesis which is subsequently realised as extra digits...
  65. ncbi Combined loss of Cdk2 and Cdk4 results in embryonic lethality and Rb hypophosphorylation
    Cyril Berthet
    National Cancer Institute, Mouse Cancer Genetics Program, NCI Frederick, Building 560 22 56, 1050 Boyles Street, Frederick, Maryland 21702, USA
    Dev Cell 10:563-73. 2006
    ..Our results demonstrate that Cdk2 and Cdk4 cooperate to phosphorylate Rb in vivo and to couple the G1/S phase transition to mitosis via E2F-dependent regulation of gene expression...
  66. ncbi Changes in motility, gene expression and actin dynamics: Cdk6-induced cytoskeletal changes associated with differentiation in mouse astrocytes
    Peter Slomiany
    Department of Biology, Connecticut College, New London, Connecticut, USA
    J Cell Biochem 99:635-46. 2006
    Cyclin dependent kinase (cdk) 4 and cdk6 have historically been understood to be D-cyclin kinases that phosphorylate pRb in the nucleus to regulate G1 phase of the cell cycle...
  67. ncbi Cell cycle and cancer: genetic analysis of the role of cyclin-dependent kinases
    M Barbacid
    Molecular Oncology Program, Centro Nacional de Investigaciones Oncologicas CNIO, Madrid, Spain
    Cold Spring Harb Symp Quant Biol 70:233-40. 2005
    ..For instance, they have illustrated that Cdk4 and Cdk6 are not essential for cell division during embryonic development except in the hematopoietic system...
  68. pmc Cdk6 blocks myeloid differentiation by interfering with Runx1 DNA binding and Runx1-C/EBPalpha interaction
    T Fujimoto
    EMBL Mouse Biology Unit, Monterotondo, Italy
    EMBO J 26:2361-70. 2007
    ..We here show that cyclin-dependent kinase 6 (Cdk6) is specifically expressed in proliferating hematopoietic progenitor cells, and that Cdk6 inhibits transcriptional ..
  69. ncbi The LxCxE pRb interaction domain of cyclin D1 is dispensable for murine development
    Mark W Landis
    Molecular Oncology Research Institute, Tufts New England Medical Center, Boston, Massachusetts 02111, USA
    Cancer Res 67:7613-20. 2007
    ....
  70. ncbi [Identification of new protein kinase genes, similar to kinases of the cdc2 family and expressed in murine hematopoietic stem cells]
    M A Ershler
    Dokl Akad Nauk 324:893-7. 1992
  71. pmc Lineage specific composition of cyclin D-CDK4/CDK6-p27 complexes reveals distinct functions of CDK4, CDK6 and individual D-type cyclins in differentiating cells of embryonic origin
    V Bryja
    Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic
    Cell Prolif 41:875-93. 2008
    ..This article is to study the role of G(1)/S regulators in differentiation of pluripotent embryonic cells...
  72. doi Stage-specific control of neural crest stem cell proliferation by the small rho GTPases Cdc42 and Rac1
    Sebastian Fuchs
    Institute of Anatomy, University of Zurich, CH 8057 Zurich, Switzerland
    Cell Stem Cell 4:236-47. 2009
    ..Thus, our data reveal distinct mechanisms for growth control of NCSCs from different developmental stages...
  73. doi Znhit1 causes cell cycle arrest and down-regulates CDK6 expression
    Zhengmin Yang
    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China
    Biochem Biophys Res Commun 386:146-52. 2009
    Cyclin-dependent kinase 6 (CDK6) is the key element of the D-type cyclin holoenzymes which has been found to function in the regulation of G1-phase of the cell cycle and is presumed to play important roles in T cell function...
  74. pmc Distinct subcellular distribution of cyclin dependent kinase 6
    Dawn M Kohrt
    Department of Biology, Connecticut College, New London, CT 06371, USA
    Cell Cycle 8:2837-43. 2009
    ..This novel function expands the previously understood function of cdk6 as a regulator of G(1) phase of the cell cycle...
  75. doi Indirubin derivatives inhibit malignant lymphoid cell proliferation
    Amel Chebel
    Faculté Lyon Sud, Universite Lyon 1, Oullins, France
    Leuk Lymphoma 50:2049-60. 2009
    ..Taken together, these results showed that IO and, moreover, its derivative 6BIO may be potent antiproliferative agents in malignant lymphoid cells...
  76. pmc PU.1 directly regulates cdk6 gene expression, linking the cell proliferation and differentiation programs in erythroid cells
    Kevin S Choe
    Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Biol Chem 285:3044-52. 2010
    ..We reported previously that the G(1) phase-specific cyclin-dependent kinase 6 (CDK6) also blocks erythroid differentiation. We now report that PU...

Research Grants2

  1. INTEGRATION OF STRESS AND MITOGEN SIGNALING
    Jonathan Cooper; Fiscal Year: 2001
    ..4) To map the interactions between ERK and Msk using approaches such at the two-hybrid system. 5) To clone Mapkip108 using conventional techniques. ..
  2. Role of the JIP-1-p190RhoGEF Complex In Neuron Function
    WILLIAM ARTHUR; Fiscal Year: 2004
    ..Furthermore, the importance of the JIP-l-p190RhoGEF association in brain development and neuronal migration will be investigated by disrupting this complex in mutant mice . ..