retinoblastoma protein

Summary

Summary: Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein.

Top Publications

  1. ncbi Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence
    Masashi Narita
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
    Cell 113:703-16. 2003
  2. 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
  3. ncbi Cellular senescence as a tumor-suppressor mechanism
    J Campisi
    Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA
    Trends Cell Biol 11:S27-31. 2001
  4. pmc Transient inactivation of Rb and ARF yields regenerative cells from postmitotic mammalian muscle
    Kostandin V Pajcini
    Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
    Cell Stem Cell 7:198-213. 2010
  5. ncbi RB and cell cycle progression
    C Giacinti
    Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA 19122, USA
    Oncogene 25:5220-7. 2006
  6. ncbi The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product
    N Dyson
    Cold Spring Harbor Laboratory, NY 11724
    Science 243:934-7. 1989
  7. ncbi Native E2F/RBF complexes contain Myb-interacting proteins and repress transcription of developmentally controlled E2F target genes
    Michael Korenjak
    Lehrstuhl für Molekularbiologie, Adolf Butenandt Institut, Ludwig Maximilians Universitat, Munchen, Germany
    Cell 119:181-93. 2004
  8. pmc Acetylation of Rb by PCAF is required for nuclear localization and keratinocyte differentiation
    Adam Pickard
    Centre for Cancer Research and Cell Biology, Queen s University Belfast, Belfast, BT9 7BL, UK
    J Cell Sci 123:3718-26. 2010
  9. ncbi Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts
    David W Fry
    Cancer Pharmacology, Pfizer Global Research and Development, Ann Arbor, Michigan 48105, USA
    Mol Cancer Ther 3:1427-38. 2004
  10. ncbi The Rb/E2F pathway and cancer
    J R Nevins
    Department of Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Hum Mol Genet 10:699-703. 2001

Detail Information

Publications295 found, 100 shown here

  1. ncbi Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence
    Masashi Narita
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
    Cell 113:703-16. 2003
    ..These results provide a molecular explanation for the stability of the senescent state, as well as new insights into the action of Rb as a tumor suppressor...
  2. 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
    ..Genetic alterations affecting p16(INK4a) and cyclin D1, proteins that govern phosphorylation of the retinoblastoma protein (RB) and control exit from the G1 phase of the cell cycle, are so frequent in human cancers that ..
  3. ncbi Cellular senescence as a tumor-suppressor mechanism
    J Campisi
    Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA
    Trends Cell Biol 11:S27-31. 2001
    ..Recent findings have revealed the complexities of the senescence phenotype and unexpected possible consequences for the organism...
  4. pmc Transient inactivation of Rb and ARF yields regenerative cells from postmitotic mammalian muscle
    Kostandin V Pajcini
    Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
    Cell Stem Cell 7:198-213. 2010
    ..These results show that differentiation of mammalian cells is reversed by inactivation of Arf and Rb and support the hypothesis that Arf evolved at the expense of regeneration...
  5. ncbi RB and cell cycle progression
    C Giacinti
    Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA 19122, USA
    Oncogene 25:5220-7. 2006
    ..Functional inactivation of pRb by viral oncoprotein binding is also shown in many neoplasias such as cervical cancer, mesothelioma and AIDS-related Burkitt's lymphoma...
  6. ncbi The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product
    N Dyson
    Cold Spring Harbor Laboratory, NY 11724
    Science 243:934-7. 1989
    ..These results suggest that these three DNA viruses may utilize similar mechanisms in transformation and implicate RB binding as a possible step in human papilloma virus-associated carcinogenesis...
  7. ncbi Native E2F/RBF complexes contain Myb-interacting proteins and repress transcription of developmentally controlled E2F target genes
    Michael Korenjak
    Lehrstuhl für Molekularbiologie, Adolf Butenandt Institut, Ludwig Maximilians Universitat, Munchen, Germany
    Cell 119:181-93. 2004
    ..These results reveal an extensive evolutionary conservation of specific pRb repressor complexes that physically combine subunits with established roles in the regulation of transcription, DNA replication, and chromatin structure...
  8. pmc Acetylation of Rb by PCAF is required for nuclear localization and keratinocyte differentiation
    Adam Pickard
    Centre for Cancer Research and Cell Biology, Queen s University Belfast, Belfast, BT9 7BL, UK
    J Cell Sci 123:3718-26. 2010
    Although the retinoblastoma protein (Rb) functions as a checkpoint in the cell cycle, it also regulates differentiation...
  9. ncbi Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts
    David W Fry
    Cancer Pharmacology, Pfizer Global Research and Development, Ann Arbor, Michigan 48105, USA
    Mol Cancer Ther 3:1427-38. 2004
    ..The results indicate that inhibition of Cdk4/6 alone is sufficient to cause tumor regression and a net reduction in tumor burden in some tumors...
  10. ncbi The Rb/E2F pathway and cancer
    J R Nevins
    Department of Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Hum Mol Genet 10:699-703. 2001
    ..Questions remain, however, as to the specific role played by individual activities within the pathway in the control of cell growth and their participation in the development of cancer...
  11. 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
    The retinoblastoma protein (pRb) acts to constrain the G1-S transition in mammalian cells. Phosphorylation of pRb in G1 inactivates its growth-inhibitory function, allowing for cell cycle progression...
  12. 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
    ....
  13. ncbi Human embryonic stem cells exhibit increased propensity to differentiate during the G1 phase prior to phosphorylation of retinoblastoma protein
    Yogev Sela
    Sohnis and Forman Families Center for Stem Cell and Tissue Regeneration Research, Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel
    Stem Cells 30:1097-108. 2012
    ..These results provide direct evidence for increased propensity of hESCs to differentiate in G1 and suggest a role for neighboring cells in preventing differentiation of hESCs as they pass through a differentiation sensitive, G1 phase...
  14. pmc Rb regulates fate choice and lineage commitment in vivo
    Eliezer Calo
    David H Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    Nature 466:1110-4. 2010
    ..Numerous functions have been ascribed to the product of the human RB1 gene, the retinoblastoma protein (pRb)...
  15. ncbi The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases
    J W Harper
    Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030
    Cell 75:805-16. 1993
    ..Cotransfection experiments indicate that CIP1 and SV40 T antigen function in a mutually antagonistic manner to control cell cycle progression...
  16. ncbi The Pezcoller lecture: cancer cell cycles revisited
    C J Sherr
    Howard Hughes Medical Institute and Department of Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Cancer Res 60:3689-95. 2000
    ..Lesions in the p16--cyclin D-CDK4--Rb and ARF--Mdm2--p53 pathways occur so frequently in cancer, regardless of patient age or tumor type, that they appear to be part of the life history of most, if not all, cancer cells...
  17. pmc Loss of Rb proteins causes genomic instability in the absence of mitogenic signaling
    Tanja van Harn
    Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    Genes Dev 24:1377-88. 2010
    ..This mechanism may allow premalignant tumor cells to acquire additional genetic alterations that promote tumorigenesis...
  18. ncbi Inactivation of the p53 pathway in retinoblastoma
    Nikia A Laurie
    Department of Developmental Neurobiology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Nature 444:61-6. 2006
    ..In addition, they support the idea that MDMX is a specific chemotherapeutic target for treating retinoblastoma...
  19. ncbi MDM2 promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma protein
    Patima Sdek
    Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118, USA
    Mol Cell 20:699-708. 2005
    Inactivation of retinoblastoma protein (Rb) plays a critical role in the development of human malignancies. It has been shown that Rb is degraded through a proteasome-dependent pathway, yet the mechanism is largely unclear...
  20. ncbi Cell-cycle inhibitors: three families united by a common cause
    A Vidal
    Laboratory of Cell Cycle Regulation, Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Gene 247:1-15. 2000
    ..We will discuss the interrelationships between Cip/Kip inhibitors and the components of the pRb pathway, and how their activities ultimately regulate cell proliferation...
  21. ncbi The retinoblastoma tumour suppressor in development and cancer
    Marie Classon
    MGH Cancer Center, Building 149, 13th Street, Room 7330, Charlestown, Massachusetts 02129, USA
    Nat Rev Cancer 2:910-7. 2002
    ..Recent studies of knockout mice and cells that lack one or more of these proteins have begun to clarify their various context-specific functions and the unique activity of this tumour suppressor...
  22. ncbi The RB and p53 pathways in cancer
    Charles J Sherr
    Howard Hughes Medical Institute, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Cancer Cell 2:103-12. 2002
    ..Most prominent among the regulators disrupted in cancer cells are two tumor suppressors, the retinoblastoma protein (RB) and the p53 transcription factor...
  23. ncbi An intact retinoblastoma protein-binding site in Merkel cell polyomavirus large T antigen is required for promoting growth of Merkel cell carcinoma cells
    Roland Houben
    Department of Dermatology, University Hospital Wurzburg, Wurzburg, Germany
    Int J Cancer 130:847-56. 2012
    ..Notably, introduction of a mutation in the LTA protein interfering with LTA binding to the retinoblastoma protein (RB) ablated this rescue...
  24. 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...
  25. ncbi The retinoblastoma-histone deacetylase 3 complex inhibits PPARgamma and adipocyte differentiation
    Lluis Fajas
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS INSERM ULP, 67404 Illkirch, France
    Dev Cell 3:903-10. 2002
    The retinoblastoma protein (RB) has previously been shown to facilitate adipocyte differentiation by inducing cell cycle arrest and enhancing the transactivation by the adipogenic CCAAT/enhancer binding proteins (C/EBP)...
  26. pmc E2f1-3 switch from activators in progenitor cells to repressors in differentiating cells
    Jean Leon Chong
    Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA
    Nature 462:930-4. 2009
    In the established model of mammalian cell cycle control, the retinoblastoma protein (Rb) functions to restrict cells from entering S phase by binding and sequestering E2f activators (E2f1, E2f2 and E2f3), which are invariably portrayed ..
  27. pmc Origin of bistability underlying mammalian cell cycle entry
    Guang Yao
    Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721, USA
    Mol Syst Biol 7:485. 2011
    ..Our findings suggested basic design principles for the robust control of the bistable cell cycle entry at the R-point...
  28. pmc Human papillomavirus type 16 E7 oncoprotein associates with the cullin 2 ubiquitin ligase complex, which contributes to degradation of the retinoblastoma tumor suppressor
    Kyungwon Huh
    The Channing Laboratory 861, Brigham and Women s Hospital, 181 Longwood Avenue, Boston, MA 02115, USA
    J Virol 81:9737-47. 2007
    ..Hence, we propose that the HPV16 E7-associated cullin 2 ubiquitin ligase complex contributes to aberrant degradation of the pRB tumor suppressor in HPV16 E7-expressing cells...
  29. ncbi Alterations of RB1, p53 and Wnt pathways in hepatocellular carcinomas associated with hepatitis C, hepatitis B and alcoholic liver cirrhosis
    Yoshihiro Edamoto
    Unit of Molecular Pathology, International Agency for Research on Cancer IARC, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France
    Int J Cancer 106:334-41. 2003
    ..e., chronic liver injury and cirrhosis, but tumors associated with alcoholism had more frequent alterations in the RB1 and p53 pathways than those caused by HCV infection...
  30. ncbi Mitogen-activated protein kinase p38 defines the common senescence-signalling pathway
    Hiroaki Iwasa
    Laboratory of Molecular and Cellular Assembly, Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Midori ku, Yokohama 226 8501, Japan
    Genes Cells 8:131-44. 2003
    ..However, it remains unclear how a common set of senescence phenotypes is indistinguishably induced in various types of senescence...
  31. pmc Loss of pRB causes centromere dysfunction and chromosomal instability
    Amity L Manning
    Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts 02129, USA
    Genes Dev 24:1364-76. 2010
    ..By monitoring chromosome segregation, we show that depletion of the retinoblastoma protein (pRB) causes rates of missegregation comparable with those seen in CIN tumor cells...
  32. pmc A kinase shRNA screen links LATS2 and the pRB tumor suppressor
    Katrin Tschop
    Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    Genes Dev 25:814-30. 2011
    ..However, little is known about the specific pathways that cooperate with the Retinoblastoma protein (pRB) and the variables that influence pRB's ability to arrest tumor cells...
  33. pmc Abrogated response to cellular stress identifies DCIS associated with subsequent tumor events and defines basal-like breast tumors
    Mona L Gauthier
    Department of Pathology, University of California, San Francisco, CA 94143, USA
    Cancer Cell 12:479-91. 2007
    ..Assessment of these biomarkers in DCIS begins to allow prediction of tumor formation years before it actually occurs...
  34. ncbi Rb interacts with histone deacetylase to repress transcription
    R X Luo
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Cell 92:463-73. 1998
    ....
  35. ncbi Synergy of p53 and Rb deficiency in a conditional mouse model for metastatic prostate cancer
    Zongxiang Zhou
    Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853 6401, USA
    Cancer Res 66:7889-98. 2006
    ..The new genetically defined model should be particularly valuable for providing new molecular insights into the pathogenesis of human prostate cancer...
  36. ncbi G1 cell cycle progression and the expression of G1 cyclins are regulated by PI3K/AKT/mTOR/p70S6K1 signaling in human ovarian cancer cells
    Ning Gao
    1820 MBR Cancer Center and Dept of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 9300, USA
    Am J Physiol Cell Physiol 287:C281-91. 2004
    ..These results indicate that PI3K mediates G(1) progression and cyclin expression through activation of an AKT/mTOR/p70S6K1 signaling pathway in the ovarian cancer cells...
  37. pmc Identification of a Drosophila Myb-E2F2/RBF transcriptional repressor complex
    Peter W Lewis
    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 3204, USA
    Genes Dev 18:2929-40. 2004
    ..These and other data now link together the Myb and E2F2 complexes in higher-order assembly to specific chromosomal sites for the regulation of transcription...
  38. pmc Structures of inactive retinoblastoma protein reveal multiple mechanisms for cell cycle control
    Jason R Burke
    Department of Chemistry and Biochemistry, University of California at Santa Cruz, Santa Cruz, California 95064, USA
    Genes Dev 26:1156-66. 2012
    Cyclin-dependent kinase (Cdk) phosphorylation of the Retinoblastoma protein (Rb) drives cell proliferation through inhibition of Rb complexes with E2F transcription factors and other regulatory proteins...
  39. ncbi Rb enhances p160/SRC coactivator-dependent activity of nuclear receptors and hormone responsiveness
    Eric Batsche
    Laboratoire de Genetique Moleculaire, Institut de Recherches Cliniques de Montreal, Quebec, Canada
    J Biol Chem 280:19746-56. 2005
    ..Increased Rb expression upon cell differentiation may promote differentiated functions, at least in part, by potentiation of NR activity...
  40. pmc MicroRNA-449 and microRNA-34b/c function redundantly in murine testes by targeting E2F transcription factor-retinoblastoma protein (E2F-pRb) pathway
    Jianqiang Bao
    Department of Histology and Embryology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
    J Biol Chem 287:21686-98. 2012
    ..demonstrated that miR-449 shared a cohort of target genes that belong to the E2F transcription factor-retinoblastoma protein pathway with the miR-34 family, and levels of miR-34b/c were significantly up-regulated in miR-449-null ..
  41. pmc Dissecting the unique role of the retinoblastoma tumor suppressor during cellular senescence
    Agustin Chicas
    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
    Cancer Cell 17:376-87. 2010
    ..Our results identify a nonredundant RB effector function that may contribute to tumor suppression and reveal how loss of RB and p53 cooperate to bypass senescence...
  42. pmc The retinoblastoma protein induces apoptosis directly at the mitochondria
    Keren I Hilgendorf
    David H Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Genes Dev 27:1003-15. 2013
    The retinoblastoma protein gene RB-1 is mutated in one-third of human tumors. Its protein product, pRB (retinoblastoma protein), functions as a transcriptional coregulator in many fundamental cellular processes...
  43. ncbi LINC, a human complex that is related to pRB-containing complexes in invertebrates regulates the expression of G2/M genes
    Fabienne Schmit
    Department of Physiological Chemistry I, Biocenter, University of Wurzburg, Wurzburg, Germany
    Cell Cycle 6:1903-13. 2007
    ..In S-phase, LINC selectively binds to the promoters of G2/M genes whose products are required for mitosis and plays an important role in their cell cycle dependent activation...
  44. pmc A requirement for MCM7 and Cdc45 in chromosome unwinding during eukaryotic DNA replication
    Marcin Pacek
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA
    EMBO J 23:3667-76. 2004
    ..A fragment of the retinoblastoma protein, Rb(1-400), was used to neutralize MCM7, and antibodies were used to neutralize Cdc45...
  45. pmc TDP-43 regulates retinoblastoma protein phosphorylation through the repression of cyclin-dependent kinase 6 expression
    Youhna M Ayala
    International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34012 Trieste, Italy
    Proc Natl Acad Sci U S A 105:3785-9. 2008
    ..in TDP-43-depleted cells is accompanied by an increase in phosphorylation of two of its major targets, the retinoblastoma protein pRb and pRb-related protein pRb2/p130...
  46. pmc RB1, development, and cancer
    Meenalakshmi Chinnam
    Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York, USA
    Curr Top Dev Biol 94:129-69. 2011
    ..Through regulation of these processes, RB1 plays a uniquely prominent role in normal development and cancer...
  47. pmc Mitotic chromosome condensation mediated by the retinoblastoma protein is tumor-suppressive
    Courtney H Coschi
    London Regional Cancer Program, University of Western Ontario, London, Ontario, Canada
    Genes Dev 24:1351-63. 2010
    ..In this report, we demonstrate that the retinoblastoma protein (pRB), a well-known regulator of progression through the G1 phase of the cell cycle, plays a critical role ..
  48. pmc Local mesenchymal stem/progenitor cells are a preferential target for initiation of adult soft tissue sarcomas associated with p53 and Rb deficiency
    Jinhyang Choi
    Department of Biomedical Sciences, Cornell University, T2 014A VRT Campus Road, Ithaca, NY 14853 6401, USA
    Am J Pathol 177:2645-58. 2010
    ..Taken together, our studies indicate that local Sca-1low dermal mesenchymal stem/progenitor cells are preferential targets for malignant transformation associated with deficiencies in both p53 and Rb...
  49. ncbi The retinoblastoma protein pathway and the restriction point
    J Bartek
    Danish Cancer Society, Division of Cancer Biology, Strandboulevarden 49, DK 2100 Copenhagen, Denmark
    Curr Opin Cell Biol 8:805-14. 1996
    The emerging role of the retinoblastoma protein (pRb) as a major controller of the restriction point has been supported by recent discoveries, including pRb's ability to repress gene transcription by all three RNA polymerases, which ..
  50. ncbi Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin
    Susana Gonzalo
    Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Madrid E 28029, Spain
    Nat Cell Biol 7:420-8. 2005
    ..These observations indicate that the RB1 family is involved in maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin, linking tumour suppression and the epigenetic definition of chromatin...
  51. ncbi Binding of pRB to the PHD protein RBP2 promotes cellular differentiation
    Elizaveta V Benevolenskaya
    Dana Farber Cancer Institute and Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 18:623-35. 2005
    ..Our results suggest that promotion of differentiation by pRB involves neutralization of free RBP2 and transcriptional activation of RBP2 targets linked to euchromatin maintenance...
  52. 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
    ..In addition, E2F activity appears to be directly regulated by the action of retinoblastoma protein (RB) and RB-related proteins and indirectly regulated through the action of G1 cyclins and associated ..
  53. pmc Shigella flexneri type III secretion system effectors OspB and OspF target the nucleus to downregulate the host inflammatory response via interactions with retinoblastoma protein
    Daniel V Zurawski
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
    Mol Microbiol 71:350-68. 2009
    ..Both GST-OspB and GST-OspF coprecipitated retinoblastoma protein from host cell lysates...
  54. pmc A Suv39h-dependent mechanism for silencing S-phase genes in differentiating but not in cycling cells
    Slimane Ait-Si-Ali
    UPR 9079 CNRS Labellisée Ligue Nationale Contre le Cancer, Institut Andre Lwoff, Villejuif, France
    EMBO J 23:605-15. 2004
    ..Thus, appropriately timed H3K9 methylation by Suv39h seems to be part of the control switch for exiting the cell cycle and entering differentiation...
  55. pmc p53 down-regulates CHK1 through p21 and the retinoblastoma protein
    V Gottifredi
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Mol Cell Biol 21:1066-76. 2001
    ..Our results identify a new repression target of p53 and suggest that p53 and CHK1 play interdependent and complementary roles in regulating both the arrest and resumption of G2 after DNA damage...
  56. ncbi Molecular mechanisms of E2F-dependent activation and pRB-mediated repression
    Maxim V Frolov
    Massachusetts General Hospital Cancer Center, Bldg 149, 13th Street, Charlestown, MA 02129, USA
    J Cell Sci 117:2173-81. 2004
    ..Such repression is evident in both actively proliferating cells and in cells that have withdrawn from the cell cycle...
  57. ncbi p130/p107/p105Rb-dependent transcriptional repression during DNA-damage-induced cell-cycle exit at G2
    Mark W Jackson
    Department of Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    J Cell Sci 118:1821-32. 2005
    ....
  58. ncbi Reduced stability of retinoblastoma protein by gankyrin, an oncogenic ankyrin-repeat protein overexpressed in hepatomas
    H Higashitsuji
    Department of Clinical Molecular Biology, Faculty of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo ku, Kyoto, 606 8507, Japan
    Nat Med 6:96-9. 2000
    ..These results demonstrate the importance of ubiquitin-proteasome pathway in the regulation of cell growth and oncogenic transformation, and indicate that gankyrin overexpression contributes to hepatocarcinogenesis by destabilizing RB1...
  59. pmc Retinoblastoma protein functions as a molecular switch determining white versus brown adipocyte differentiation
    Jacob B Hansen
    Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK 5230 Odense M, Denmark
    Proc Natl Acad Sci U S A 101:4112-7. 2004
    ..Here we demonstrate that the retinoblastoma protein (pRB) regulates white vs. brown adipocyte differentiation...
  60. ncbi Structure of the retinoblastoma tumour-suppressor pocket domain bound to a peptide from HPV E7
    J O Lee
    Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Nature 391:859-65. 1998
    ..The A and B boxes each contain the cyclin-fold structural motif, with the LxCxE-binding site on the B-box cyclin fold being similar to a Cdk2-binding site of cyclin A and to a TBP-binding site of TFIIB...
  61. ncbi E2F: a link between the Rb tumor suppressor protein and viral oncoproteins
    J R Nevins
    Howard Hughes Medical Institute, Section of Genetics, Duke University Medical Center, Durham, NC 27710
    Science 258:424-9. 1992
    ....
  62. ncbi Aberrant regulation of survivin by the RB/E2F family of proteins
    Yuying Jiang
    Columbus Children s Research Institute, College of Medicine and Public Health, Ohio State University, 43210, USA
    J Biol Chem 279:40511-20. 2004
    ....
  63. ncbi Emerging roles for E2F: beyond the G1/S transition and DNA replication
    Hugh Cam
    Department of Pathology, MSB 504A, New York University School of Medicine and NYU Cancer Institute, New York, NY 1001, USA
    Cancer Cell 3:311-6. 2003
    ....
  64. pmc Regulation of E2F1 activity by acetylation
    M A Martinez-Balbas
    Wellcome CRC Institute and Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK
    EMBO J 19:662-71. 2000
    ..Consistent with this, we find that the RB-associated histone deacetylase can deacetylate E2F1. These results identify acetylation as a novel regulatory modification that stimulates E2F1's activation functions...
  65. pmc Nucleoplasmic LAP2alpha-lamin A complexes are required to maintain a proliferative state in human fibroblasts
    Vanja Pekovic
    School of Biological and Biomedical Sciences, University of Durham, Durham DH1 3LE, England, UK
    J Cell Biol 176:163-72. 2007
    ..upon entry and exit from G(0) is tightly correlated with phosphorylation and subnuclear localization of retinoblastoma protein (Rb). Phosphoisoforms of Rb and LAP2alpha are down-regulated in G(0)...
  66. pmc In vivo proliferation of postmitotic cochlear supporting cells by acute ablation of the retinoblastoma protein in neonatal mice
    Yiling Yu
    Department of Developmental Neurobiology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    J Neurosci 30:5927-36. 2010
    ..Here, we acutely ablate the retinoblastoma protein (Rb), a crucial cell cycle regulator, in two subtypes of postmitotic SCs (pillar and Deiters' cells) using ..
  67. pmc Epstein-Barr virus latent antigen 3C can mediate the degradation of the retinoblastoma protein through an SCF cellular ubiquitin ligase
    Jason S Knight
    Department of Microbiology and the Tumor Virology Program, Abramson Comprehensive Cancer Center, University of Pennsylvania, 201E Johnson Pavilion, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 102:18562-6. 2005
    ..To address the role of EBV latency protein Epstein-Barr nuclear antigen 3C (EBNA3C) in regulation of the retinoblastoma protein (Rb), we transfected EBNA3C into 293, BJAB, and SAOS-2 cells...
  68. pmc Emerging roles of E2Fs in cancer: an exit from cell cycle control
    Hui Zi Chen
    Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics and Department of Molecular Genetics, The Ohio State University, Columbus, Ohio 43210, USA
    Nat Rev Cancer 9:785-97. 2009
    ....
  69. pmc The human papillomavirus E7 oncoprotein
    Margaret E McLaughlin-Drubin
    Brigham and Women s Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
    Virology 384:335-44. 2009
    ..This function is directly reflected in the transforming activities of E7, including tumor initiation and induction of genomic instability...
  70. ncbi The p16INK4a-RB pathway: molecular link between cellular senescence and tumor suppression
    Naoko Ohtani
    Division of Protein Information, Institute for Genome Research, The University of Tokushima, Tokushima, Japan
    J Med Invest 51:146-53. 2004
    ..Here we discuss the molecular mechanisms that direct cellular senescence and reveal its potential for tumor suppression...
  71. ncbi Human papillomavirus type 16 E7 up-regulates AKT activity through the retinoblastoma protein
    Craig W Menges
    Department of Biochemistry and Biophysics, University of Rochester, Rochester, New York, USA
    Cancer Res 66:5555-9. 2006
    ..Together, these data provide evidence linking inactivation of Rb by E7 in the up-regulation of AKT activity during cervical cancer progression...
  72. ncbi Spontaneous squamous cell carcinoma induced by the somatic inactivation of retinoblastoma and Trp53 tumor suppressors
    Ana Belén Martínez-Cruz
    Molecular Oncology Unit, Division of Biomedicine, Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas, Madrid, Spain
    Cancer Res 68:683-92. 2008
    ..The molecular characteristics of this model provide valuable tools to understand epidermal tumor formation and may ultimately contribute to the development of therapies for the treatment of aggressive squamous cancer...
  73. ncbi Nox4 mediates TGF-beta1-induced retinoblastoma protein phosphorylation, proliferation, and hypertrophy in human airway smooth muscle cells
    Anne Sturrock
    Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, University of Utah Health Sciences Center and Veterans Administration Medical Center, Salt Lake City, Utah 84132, USA
    Am J Physiol Lung Cell Mol Physiol 292:L1543-55. 2007
    ..Consistent with this hypothesis, TGF-beta1 increased retinoblastoma protein phosphorylation at both Ser807/811 and Ser780...
  74. pmc Hepatitis B virus X protein via the p38MAPK pathway induces E2F1 release and ATR kinase activation mediating p53 apoptosis
    Wen Horng Wang
    Department of Basic Medical Sciences, Purdue University, 625 Harrison Street, West Lafayette, IN 47907, USA
    J Biol Chem 283:25455-67. 2008
    ..In conclusion, pX sensitizes hepatocytes to p53 apoptosis via activation of the p38MAPK pathway, which couples p53 stabilization and p53 activation, by E2F1 induction and ATR activation, respectively...
  75. pmc Hematopoietic stem cell quiescence is maintained by compound contributions of the retinoblastoma gene family
    Patrick Viatour
    Department of Pediatrics, Stanford Medical School, Stanford, CA 94305, USA
    Cell Stem Cell 3:416-28. 2008
    ..The presence of a single p107 allele is sufficient to largely rescue these defects. Thus, Rb family members collectively maintain HSC quiescence and the balance between lymphoid and myeloid cell fates in the hematopoietic system...
  76. pmc CCAAT/enhancer-binding protein beta inhibits proliferation in monocytic cells by affecting the retinoblastoma protein/E2F/cyclin E pathway but is not directly required for macrophage morphology
    Romina Gutsch
    Institute of Clinical Chemistry, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    J Biol Chem 286:22716-29. 2011
    ..Inhibition of proliferation by C/EBPβ may be important for coordinated monocytic differentiation...
  77. pmc Tumor promotion by caspase-resistant retinoblastoma protein
    Helena L Borges
    Division of Hematology Oncology, Moores Cancer Center, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 102:15587-92. 2005
    ..These results suggest that RB tumor suppressor function, i.e., inhibition of proliferation, is inactivated by phosphorylation, whereas RB tumor promoting function, i.e., inhibition of apoptosis, is inactivated by caspase cleavage...
  78. ncbi Failure to phosphorylate the retinoblastoma gene product in senescent human fibroblasts
    G H Stein
    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder 80309 0347
    Science 249:666-9. 1990
    ..Both senescent and quiescent HDF contained the unphosphorylated form (p110Rb) of the retinoblastoma protein, a putative inhibitor of proliferation...
  79. ncbi Cyclin E in human cancers
    R Donnellan
    Department of Pathology, University of Natal Medical School, Durban, South Africa
    FASEB J 13:773-80. 1999
    ..These interactions are important in elucidating the mechanisms of neoplasia. They may also provide prognostic information in a wide range of common cancers. Cyclin E may even be a target for treatment of cancers in the future...
  80. ncbi Identification of senescence-associated genes and their networks under oxidative stress by the analysis of Bach1
    Kazushige Ota
    Department of Biochemistry, Tohoku University Graduate School of Medicine, Seiryo machi 2 1, Sendai, Japan
    Antioxid Redox Signal 14:2441-51. 2011
    ..Our elucidations contrast with previous reports describing monopolistic regulations of senescence by single p53 target genes...
  81. ncbi Pax-6 interactions with TATA-box-binding protein and retinoblastoma protein
    A Cvekl
    Laboratory of Molecular and Developmental Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892 2730, USA
    Invest Ophthalmol Vis Sci 40:1343-50. 1999
    ..To identify proteins that physically interact with Pax-6, a paired domain- and homeodomain (HD)-containing transcription factor that is a key regulator of eye development...
  82. pmc Cooperativity of Rb, Brca1, and p53 in malignant breast cancer evolution
    Prashant Kumar
    Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    PLoS Genet 8:e1003027. 2012
    ..Gene expression analyses demonstrate that the tumors share attributes of both Basal-like and Claudin-low signatures, two molecular subtypes encompassed by the broader, triple-negative class defined by clinical markers...
  83. ncbi Loss of RB1 induces non-proliferative retinoma: increasing genomic instability correlates with progression to retinoblastoma
    Helen Dimaras
    Department of Molecular and Medical Genetics, University of Toronto, Medical Sciences Building, 1 King s College Circle, Toronto, ON, Canada
    Hum Mol Genet 17:1363-72. 2008
    ..However, stable retinoma is rarely clinically observed because progressive genomic instability commonly leads to highly proliferative retinoblastoma...
  84. ncbi The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit
    T Durfee
    Center for Molecular Medicine Institute of Biotechnology, University of Texas Health Science Center, San Antonio 78245
    Genes Dev 7:555-69. 1993
    The retinoblastoma protein (p110RB) interacts with many cellular proteins in complexes potentially important for its growth-suppressing function...
  85. ncbi Adenovirus and cell cycle control
    Haggit Ben-Israel
    The Gonda Center of Molecular Microbiology, The Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa 31096, Israel
    Front Biosci 7:d1369-95. 2002
    ..Such "oncolytic" viruses are being tested for their ability to specifically replicate in and lyse cancer cells...
  86. ncbi Biological activities and molecular targets of the human papillomavirus E7 oncoprotein
    K Munger
    Department of Pathology and Harvard Center for Cancer Biology, Harvard Medical School, Boston, MA 02115, USA
    Oncogene 20:7888-98. 2001
    ..The transforming activities of E7 largely reflect this important function...
  87. ncbi In vitro and in vivo pharmacokinetic-pharmacodynamic relationships for the trisubstituted aminopurine cyclin-dependent kinase inhibitors olomoucine, bohemine and CYC202
    Florence I Raynaud
    Cancer Research UK Centre for Cancer Therapeutics at The Institute of Cancer Research, Haddow Laboratories, Belmont, Sutton, United Kingdom
    Clin Cancer Res 11:4875-87. 2005
    ..To investigate pharmacokinetic-pharmacodynamic relationships for the trisubstituted aminopurine cyclin-dependent kinase inhibitors olomoucine, bohemine, and CYC202 (R-roscovitine; seliciclib) in the HCT116 human colon carcinoma model...
  88. ncbi Frequent alterations of the candidate genes hMLH1, ITGA9 and RBSP3 in early dysplastic lesions of head and neck: clinical and prognostic significance
    Amlan Ghosh
    Department of Oncogene Regulation and Gynaecology Oncology, Chittaranjan National Cancer Institute, Kolkata, India
    Cancer Sci 101:1511-20. 2010
    ..Thus our data suggests that dysregulation of hMLH1, ITGA9, and RBSP3 associated multiple cellular pathways are needed for the development of early dysplastic lesions of the head and neck...
  89. pmc NRMT is an alpha-N-methyltransferase that methylates RCC1 and retinoblastoma protein
    Christine E Schaner Tooley
    Department of Microbiology, Center for Cell Signaling, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA
    Nature 466:1125-8. 2010
    ..identification of numerous new methylation targets, including SET (also known as TAF-I or PHAPII) and the retinoblastoma protein, RB...
  90. pmc Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth
    Kuei Chun Wang
    Department of Bioengineering and Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 107:3234-9. 2010
    ..Our findings indicate that PS suppresses EC proliferation through the regulation of miR-23b and provide insights into the role of miRs in mechanotransduction...
  91. ncbi Merkel cell polyomavirus infection, large T antigen, retinoblastoma protein and outcome in Merkel cell carcinoma
    Harri Sihto
    Laboratory of Molecular Oncology, Biomedicum Helsinki, Finland
    Clin Cancer Res 17:4806-13. 2011
    ..Polyomaviruses repress tumor suppressor proteins, thus influencing cell-cycle progression, but the effect of MCPyV on the key cell-cycle regulating proteins is poorly understood...
  92. pmc Intracellular signaling and hepatocellular carcinoma
    Polina Iakova
    Department of Pathology and Immunology and Huffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, United States
    Semin Cancer Biol 21:28-34. 2011
    ..Particularly, recent reports suggest a critical role of histone deacetylase 1, HDAC1, in the development of HCC through the interactions with transcription factors such as C/EBP family proteins...
  93. pmc Rb/E2F regulates expression of neogenin during neuronal migration
    Matthew G Andrusiak
    Department of Cellular Molecular Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, Ontario K1H 8M5, Canada
    Mol Cell Biol 31:238-47. 2011
    ..These studies identify a novel mechanism through which Rb regulates transcription of a gene beyond the classical E2F targets to regulate events distinct from cell cycle progression...
  94. pmc Somatic tetraploidy in specific chick retinal ganglion cells induced by nerve growth factor
    Sandra M Morillo
    Department of Molecular, Cellular and Developmental Neurobiology, Instituto Cajal, Consejo Superior de Investigaciones Cientificas, Avenida Doctor Arce 37, E 28002 Madrid, Spain
    Proc Natl Acad Sci U S A 107:109-14. 2010
    ..cells that express both the neurotrophin receptor p75 and the E2F1 transcription factor, but that lack the retinoblastoma protein. Many of these neurons avoid G2/M transition and remain alive in the retina as tetraploid cells with large ..
  95. pmc Retinoblastoma protein is essential for early meiotic events in Arabidopsis
    Zhong Chen
    Temasek Life Sciences Laboratory, Singapore
    EMBO J 30:744-55. 2011
    ..have analysed the role of RBR (retinoblastoma related), the Arabidopsis homologue of the tumour suppressor Retinoblastoma protein (pRb), during meiosis. We characterise the rbr-2 mutation, which causes a loss of RBR in male meiocytes...
  96. ncbi Interaction between the retinoblastoma protein and the oncoprotein MDM2
    Z X Xiao
    Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nature 375:694-8. 1995
    ..Therefore, both pRB and p53 can be subjected to negative regulation by the product of a single cellular protooncogene...
  97. ncbi Distinct pattern of E2F1 expression in human lung tumours: E2F1 is upregulated in small cell lung carcinoma
    B Eymin
    Groupe de Recherche sur le Cancer du Poumon, EA 2021, Equipe INSERM 9924, Institut Albert Bonniot, 38706 La Tronche Cedex, France
    Oncogene 20:1678-87. 2001
    ..0001) as well as a Bcl-2:Bax ratio >1 (P<0.001). Overall, these results demonstrate a distinct pattern of E2F1 expression in human lung tumours and suggest that its deregulation could be involved in the carcinogenesis of SCLC...
  98. ncbi Taxol-induced apoptosis depends on MAP kinase pathways (ERK and p38) and is independent of p53
    S S Bacus
    Quantitative Diagnostic Laboratories, Inc, Elmhurst, Illinois 60126, USA
    Oncogene 20:147-55. 2001
    ..However, p53 may serve as a survival factor in breast carcinoma cells treated with Taxol by blocking cells in G2/M phase of the cell cycle...
  99. ncbi Honokiol causes G0-G1 phase cell cycle arrest in human prostate cancer cells in association with suppression of retinoblastoma protein level/phosphorylation and inhibition of E2F1 transcriptional activity
    Eun Ryeong Hahm
    Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Mol Cancer Ther 6:2686-95. 2007
    ..PC-3 and LNCaP cells exhibited a marked decrease in the levels of total and phosphorylated retinoblastoma protein (Rb), which correlated with the suppression of transcriptional activity of E2F1...
  100. pmc Newly identified aspects of tumor suppression by RB
    Patrick Viatour
    Department of Genetics, Stanford University, Stanford, CA 94305, USA
    Dis Model Mech 4:581-5. 2011
    ..In particular, we discuss the pro- and anti-tumorigenic roles of RB during the early stages of cancer, as well as the importance of the RB pathway in stem cells and cell fate decisions...
  101. pmc RB·E2F1 complex mediates DNA damage responses through transcriptional regulation of ZBRK1
    Ching Chun Liao
    Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
    J Biol Chem 285:33134-43. 2010
    ....

Research Grants62

  1. Vitamin D3, Interference with Androgen Signal and Inhibition of Prostate Cancer
    Bandana Chatterjee; Fiscal Year: 2013
    ..promoter that results from enhanced E2F1 interaction with Alien, prohibitin or well-known E2F1 partner Rb (retinoblastoma protein), and with Alien/prohibitin/Rb-recruited corepressors...
  2. Role of Polyamines in MYCN-Amplified Neuroblastoma
    ANDRE BACHMANN; Fiscal Year: 2009
    ..of polyamines in MYCN-amplified NB cells caused G1 cell cycle arrest and affected p27Kip1 levels, retinoblastoma protein Rb phosphorylation, and most intriguingly, blocked MYCN expression, thus providing a rationale for the ..
  3. Does the extreme variability of methadone metabolism have an epigenetic cause?
    Gavin R Schnitzler; Fiscal Year: 2010
    ..are often associated with the aberrant loss of mRNA for important tumor suppressor genes, including retinoblastoma protein (pRB) and breast cancer associated protein 1 (BRCA1)...
  4. Murine Model of HCV-Associated Human Liver Cancer
    Lishan Su; Fiscal Year: 2013
    ..and oxidative stress, and to specifically assess the role played by the targeted destruction of the retinoblastoma protein by HCV and sequestration of the tumor suppressor DDX3 by HCV core protein...
  5. Regulation of Tumor Metabolism by Retinoblastoma Protein
    Brian F Clem; Fiscal Year: 2013
    ..2. To determine the effects of Rb1 deletion on glucose/glutamine metabolism and growth of lung adenocarcinomas in vivo. 3. To correlate the loss of Rb function with changes in the 13C-glucose utilization by human lung tumors in vivo. ..
  6. Development of sd-rxRNAs as Therapy for Retinoblastoma and Other Malignancies
    Pamela Pavco; Fiscal Year: 2012
    ..The Cobrinik lab has recently shown that retinoblastoma growth is driven not only by retinoblastoma protein (RB) mutations, but also by "normal" signaling circuitry of retinal cone precursors...
  7. Condensin II/RBF
    Nicholas J Dyson; Fiscal Year: 2013
    ..This proposal investigates the normal function of the retinoblastoma protein, pRB, one of the most famous and best characterized tumor suppressors...
  8. Cyclin D1 and vitamin D signaling in oral keratinocyte pathophysiology
    Sanjay M Mallya; Fiscal Year: 2013
    ..Acting via its kinase partners CDK4 and CDK6, it results in phosphorylation of the retinoblastoma protein to effect cell cycle progression...
  9. The Regulation of PP1 in the Nucleus
    Rebecca Page; Fiscal Year: 2013
    ..the post-translational modification of p53 and MDM2 and it plays essential role in the regulation of the retinoblastoma protein in response to cellular stress, critical processes for the regulation of cancer...
  10. Genetic Interaction Between the pRB and Warts Tumor Suppressor Pathways
    Brandon Nicolay; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): The retinoblastoma protein (pRB) is very important tumor suppressor that is often mutated or inactivated during the formation of cancer...
  11. Developmental Functions of Rb family proteins
    David S Fay; Fiscal Year: 2013
    ..by applicant): Among the many pathways controlling cell proliferation and differentiation, genes of the retinoblastoma protein (pRb) regulatory network stand out as frequent, if not obligatory, targets for mutation or deregulation ..
  12. Basic Mechanisms of Human Calcific Aortic Valve Disease
    Gordon S Huggins; Fiscal Year: 2013
    ..gene SNPs with aortic valve calcification is provocative because we have previously demonstrated that the retinoblastoma protein (pRb) and CDK pathway regulate bone formation through the runx2 transcription factor and by regulating ..
  13. Structural basis for functional modulation of CBP/p300 by the HPV oncoprotein E7
    ARIANE LESLIE JANSMA; Fiscal Year: 2012
    ..will be employed to determine if high and low risk E7 bind simultaneously to TAZ2 and the tumor suppressor retinoblastoma protein (pRb)...
  14. BIOLOGICAL Function of the Retinoblastoma Gene Product
    Jean Y J Wang; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): The retinoblastoma protein, RB, is a negative regulator of cell proliferation and apoptosis. The anti- proliferation function of RB underlies its tumor suppression activity...
  15. Functions of an E1A-Associated Cellular Protein
    Bayar Thimmapaya; Fiscal Year: 2010
    ..These include p400, p300 and the highly related CBP, Retinoblastoma protein (Rb), and two Rb related proteins p107 and p130...
  16. Nuclear Lamin Functions and Human Disease
    Brian K Kennedy; Fiscal Year: 2013
    ..normal proliferation, (2) further mechanistic studies to determine why A-type lamins act to stabilize the retinoblastoma protein, and (3) exploring the links between A-type lamins and Gankyrin expression...
  17. Hematopoietic Regulation Via GATA Switches
    Emery H Bresnick; Fiscal Year: 2013
    ..hypothesize that 1-83 is defective in recruiting critical co-repressors, and residues 81-85 constitute a Retinoblastoma Protein-binding motif. We shall test whether 1-83 is compromised in specific steps leading to Gata2 repression...
  18. Cell cycle regulation by protein phosphatase 2A
    Marc C Mumby; Fiscal Year: 2012
    ..Two proteins required for these transitions are the retinoblastoma protein, which controls the expression of genes required for G1 progression and the cell division cycle 6 protein (..
  19. The Role of Rb Dephosphorylation in Apoptosis
    Nancy A Krucher; Fiscal Year: 2010
    ..The phosphorylation state of the Retinoblastoma protein (Rb) regulates the ability of this protein to control cell proliferation...
  20. Role of LEK and Rb Protein Interactions in Heart and Skeletal Muscle Development
    MARY ELLEN DEES; Fiscal Year: 2013
    ..a role of LEK proteins in a pathway critical for regulating growth and differentiation in all cells, the retinoblastoma protein (Rb) pathway...
  21. The role of pRb-dependent Ihh in osteogenesis and osteosarcoma
    CRYSTAL BRYAN; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The retinoblastoma protein (pRb) is a tumor suppressor that is found mutated or dysregulated in most human cancers. It is most commonly directly affected in retinoblastoma and osteosarcoma...
  22. Molecular Mechanisms Regulating the Retinoblastoma Protein Family
    SETH MICHAEL RUBIN; Fiscal Year: 2013
    ..It is anticipated that these studies will provide fundamental new concepts for understanding mechanisms of tumorigenesis and strategies for treating cancers that result from deregulated cell-cycle control mechanisms. ..
  23. TESTOSTERONE REPLACEMENT & PHYSICAL FUNCTION IN HIV+MEN
    Shalender Bhasin; Fiscal Year: 2005
    ..Phosphorylated retinoblastoma protein and proliferating cell nuclear antigen (PCNA) will be used as markers of satellite cell cycle events...
  24. Role of MDM2 in Cell Proliferation and Tumorigenesis
    Zhi Xiong Jim Xiao; Fiscal Year: 2010
    ..This application focuses on MDM2-mediated regulation on retinoblastoma protein (Rb)...
  25. FUNCTIONS OF RB PROTEASE(S) IN APOPTOSIS
    QING DOU; Fiscal Year: 2000
    ..abstract): The under- phosphorylated (p110/pRB), but not the phosphorylated (pI2O/ppRB), form of retinoblastoma protein (RB) serves as an endogenous inhibitor of cell proliferation, differentiation and senescence...
  26. Conditional Replicating Adenovirus for Glioma Treatment
    Juan Fueyo; Fiscal Year: 2006
    ..have previously generated a conditional replicating adenovirus, D24, unable to bind to and inactivate the retinoblastoma protein (Rb). This tumor-selective adenovirus is able to replicate in glioma cells but not in normal cells...
  27. PROLIFERATIVE EFFECTS OF CDK4 AND CDK6 DYSREGULATION
    Philip Hinds; Fiscal Year: 2006
    DESCRIPTION (provided by applicant): Inactivation of the retinoblastoma protein (pRb) is one of the most frequent events in cancer and is often the consequence of hyperactivation of regulatory cyclin D/cdk complexes...
  28. REGULATION OF INTESTINAL EPITHELIAL CELL PROLIFERATION
    John Lynch; Fiscal Year: 2004
    ..We will also demonstrate that this block is associated with hypophosphorylation of the retinoblastoma protein, and down-regulation of cyclin D1 and D2 protein...
  29. FUNCTION OF THE RETINOBLASTOMA PROTEIN
    Edward Harlow; Fiscal Year: 2002
    ..We have finished the initial characterization of these differences and in the next round of this grant will investigate the functional differences between pRB p107 and p130 in adipogenesis and in other defined differentiation systems. ..
  30. PROTEIN PHOSPHATASE 1 AND NEOPLASTIC TRNSFORMATION
    Norbert Berndt; Fiscal Year: 2004
    ..This ability depends on intact pathways that converge on the retinoblastoma protein, RB, whose major function is to prevent cells from committing to the next cell division...
  31. INTERFERON REGULATORY FACTOR 2 FUNCTIONS
    George Blanck; Fiscal Year: 2002
    ..In some cases, this defect has been attributed to loss of the retinoblastoma protein. In many other cases, lack of HLA class II induction is attributable to lack of induction of class II ..
  32. GROWTH REGULATION--SENESCENT VS NONSENESCENT CELLS
    GRETCHEN STEIN; Fiscal Year: 1999
    ..Previous studies have shown that mitogen-stimulated senescent HDF fail to phosphorylate their retinoblastoma protein (pRB) and lack c-fos, cyclin A and cdc2...
  33. MOLECULAR BASIS OF RETINAL APOPTOSIS AND RETINOBLASTOMA
    JOLENE WINDLE; Fiscal Year: 1999
    ..In addition, transgenic mice which express the human papillomavirus E7 protein (which inactivates the retinoblastoma protein) specifically in photoreceptor cells develop apoptotic retinal degeneration rather than retinoblastoma...
  34. CELL GROWTH, NA/H EXCHANGE, AND CYCLINS IN IDDM PATIEN
    Daniel Batlle; Fiscal Year: 2002
    ..The retinoblastoma protein (pRB), acting in its un- phosphorylated form, inhibits cell-cycle progression at the GS/1 boundary...
  35. ANDROGEN RECEPTOR REGULATION OF PROSTATE CANCER GROWTH
    Samir Taneja; Fiscal Year: 2002
    ..expression of cyclin A and cyclin dependent kinases (cdk's) 1 and 2, and decreased expression of the retinoblastoma protein (Rb)...
  36. Cell Cycle Dependent Mechanisms of Renal Hypertrophy
    Daniel Riley; Fiscal Year: 2006
    ..Using unique transgenic mice overexpressing retinoblastoma protein (Rb) and mesangial cells expressing Rb from a tetracycline-confrollable promoter system, we have ..
  37. IRF 1 AND PROLACTIN IN T CELL ACTIVATION
    Li Yuan Yu Lee; Fiscal Year: 1999
    ..and activator of transcription" or Stat, and the cell cycle-regulated transcription complex containing retinoblastoma protein (Rb) as possible PRL signaling molecules at the IRF-i promoter...
  38. INVESTIGATION OF THE CELLULAR P300 PROTEIN
    Edward Harlow; Fiscal Year: 1993
    ..but the interaction with p3OO is genetically and physically distinct from ElA's association with the retinoblastoma protein and human cyclin A. Although p300 has many interesting properties, it has proven to be difficult to study...
  39. MONOCLONAL ANTIBODY AGAINST RETINOBLASTOMA GENE PRODUCT
    CHUNMING HUANG; Fiscal Year: 1991
    ..3. To study the extent of RB defects in established tumor cell lines. 4. To survey the extent of RB defects in various primary tumors...
  40. ECTOPIC EXPRESSION OF THE RETINOBLASTOMA GENE IN MICE
    STEPHEN HEDRICK; Fiscal Year: 1993
    ..These experiments will provide information concerning the biological function of at least one "tumor suppressor" gene and provide a model for studying the onset of malignancy in patients with a heterozygous defect in the RB gene...
  41. TWO NOVEL CPLA2 BINDING PROTEINS AND CELL DEATH
    Alice Sheridan; Fiscal Year: 2005
    ..PLIP expression is associated with a marked decrease in GO/G1 phase cells associated with a decrease in retinoblastoma protein. Endogenous PLIP is increased in mesangial cells following genotoxic stress suggesting that PLIP may ..
  42. FUNCTIONAL ANALYSIS OF THE RETINAL REGULATORY PROTEIN RB
    JAMES HARBOUR; Fiscal Year: 2002
    ..where many important contributions have been made in understanding the structure and function of the retinoblastoma protein (Rb) in health and disease...
  43. Transcriptional Responses in Neurodegenerative Diseases
    Robert Bowser; Fiscal Year: 2007
    ..Key protein components of the cell cycle regulated death of neurons include p53, E2F1 and the retinoblastoma protein (pRb)...
  44. ARF MDM2 P53 TUMOR SUPPRESSION PATHWAY
    Yanping Zhang; Fiscal Year: 2005
    ..p16INK4a inhibits the activity of cyclin D-dependent kinases (CDK4 and CDK6), thereby maintaining the retinoblastoma protein (Rb) in its growth suppressive state...
  45. PHOSPHORYLATION OF THE RETINOBLASTOMA PROTEIN
    ANTE LUNDBERG; Fiscal Year: 1999
    ..Current research suggests that this decision is determined by hyperphosphorylation of the retinoblastoma protein (pRB), but the precise molecular mechanisms by which this occurs remain unclear...
  46. Rb, p53, & Bcl-2 Proteins in Apoptosis
    STEVEN WEINTRAUB; Fiscal Year: 2007
    ..Finally, we found that at least in some cells, the retinoblastoma protein mediates the suppression of Bcl-xL deamidation...
  47. Molecular Analysis of Viral Cyclin
    Stephen Brandt; Fiscal Year: 2006
    ..K-cyclin binds a DNA consensus found in promoters regulated by retinoblastoma protein/Sp/Kruppel-like factor (Rb/Sp/KLF) complexes...
  48. FUNCTION OF PRB RELATED PROTEINS IN SKELETAL DEVELOPMENT
    David Cobrinik; Fiscal Year: 2001
    ..The retinoblastoma protein (pRB)-related p107 and p130 proteins are implicated in these processes, since mouse embryos that are ..
  49. E2F4 and RB in differentiation control and tumorigenesis
    Jacqueline A Lees; Fiscal Year: 2010
    ..The retinoblastoma protein (pRB) inhibits cellular proliferation by binding to the E2F transcription factors and thereby blocks the ..
  50. RETINOBLASTOMA PROTEIN IN DROSOPHILA
    Wei Du; Fiscal Year: 2005
    ..abstract_text> ..
  51. EXPRESSION AND FUNCTIONS OF MDM2 PROTEINS
    MARY PERRY; Fiscal Year: 2001
    ..of cancer because MDM2 proteins antagonize the functions of two tumor suppressor proteins, p53 and the retinoblastoma protein. Overexpression of mdm2 can reverse the block in progression through the cell cycle mediated by either Rb ..
  52. MECHANISMS OF REPRESSION BY THE RETINOBLASTOMA PROTEIN
    STEVEN WEINTRAUB; Fiscal Year: 2000
    DESCRIPTION (Adapted from applicant's abstract and specific aims): Retinoblastoma protein (Rb) function appears to be essential in the differentiation of airway epithelium as well as several other tissues...
  53. IGFS AND SKELETAL MUSCLE CELL DIFFERENTIATION
    Saleh Adi; Fiscal Year: 2000
    ..the decision of skeletal muscle cells to grow or differentiate by regulating the phosphorylation of retinoblastoma protein (pRB), a key regulator of the cell cycle machinery, which when phosphorylated promotes growth but when ..
  54. MECHANISM OF ACTION OF THE SKI ONCOGENE
    Michael Hayman; Fiscal Year: 2005
    ..Ski interacts with the retinoblastoma protein, (Rb), and effects E2F regulated transcription...
  55. RETINOBLASTOMA PROTEIN IN LUNG AND OTHER TISSUES
    Douglas Dean; Fiscal Year: 2002
    ..We propose additional studies to further examine the mechanism of action and the role of Rb in cultured cells and transgenic mice. ..
  56. Nuclear Function of the c-Abl Protooncoprotien
    Jean Wang; Fiscal Year: 2007
    ..Aim 6 will implement two strategies to identify other nuclear substrates of c-Abl. Identification of substrates will provide further information on the biological function of the c-Abl tyrosine kinase. ..
  57. Protein Tyrosine Kinases in Leiomyomata Uteri
    Jean Wang; Fiscal Year: 2007
    ..Information gathered from the proposed research may therefore lead to the development of new therapeutics to control the growth of fibroids. ..
  58. Modulation of Aflatoxin B1-induced hepatocarcinogenesis by RB loss
    Erik Knudsen; Fiscal Year: 2007
    ..These studies will identify critical facets of RB function in vivo and delineate specific consequences of RB loss that are germane to tumor formation following genotoxic insult. [unreadable] [unreadable] [unreadable]..
  59. Using Synthetic Lethality to Select Cancer Drug Targets
    William Kaelin; Fiscal Year: 2005
    ..Moreover, they may establish a new paradigm for the selection of anticancer drug targets based on inactivating mutations of TSG. ..
  60. Real-Time Imaging of Hypoxia based on VHL Activity
    William Kaelin; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  61. A Luciferase Fusion Protein Library to Identify & Monitor Ubiquitylation Targets
    William Kaelin; Fiscal Year: 2008
    ..Reisolation of HIF in aims 2 and 3 would constitute proof of concept with respect to the potential utility of this approach. ..
  62. Apoptosis Signaling: BH3 to BH123 Proteins
    GOVINDASWAMY CHINNADURAI; Fiscal Year: 2008
    ..The knowledge gained would be valuable in modulating the activity of BAX in cancer and in degenerative diseases. ..