Trp53

Summary

Gene Symbol: Trp53
Description: transformation related protein 53
Alias: Tp53, bbl, bfy, bhy, p44, p53, cellular tumor antigen p53, mutant p53, p53 cellular tumor antigen, tumor suppressor p53, tumor supressor p53
Species: mouse

Top Publications

  1. ncbi Mdm2 promotes the rapid degradation of p53
    Y Haupt
    Lautenberg Center for General and Tumor Immunology, The Hebrew University Haddassah Medical School, Jerusalem, Israel
    Nature 387:296-9. 1997
  2. ncbi Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
    M Serrano
    Cold Spring Harbor Laboratory, New York 11724, USA
    Cell 88:593-602. 1997
  3. ncbi Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
    L A Donehower
    Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030
    Nature 356:215-21. 1992
  4. ncbi Tumor spectrum analysis in p53-mutant mice
    T Jacks
    Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139
    Curr Biol 4:1-7. 1994
  5. ncbi Regulation of p53 stability by Mdm2
    M H Kubbutat
    ABL Basic Research Program, NCI FCRDC, Frederick, Maryland 21702 1201, USA
    Nature 387:299-303. 1997
  6. ncbi Oncogene-induced senescence as an initial barrier in lymphoma development
    Melanie Braig
    Charité Universitätsmedizin Berlin Haematology Oncology, 13353 Berlin, Germany
    Nature 436:660-5. 2005
  7. ncbi The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation
    J Momand
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, New Jersey 08544 1014
    Cell 69:1237-45. 1992
  8. ncbi p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression
    Tongxiang Lin
    Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0322, USA
    Nat Cell Biol 7:165-71. 2005
  9. pmc p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation
    Hongwu Zheng
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 455:1129-33. 2008
  10. pmc Distinct p53 transcriptional programs dictate acute DNA-damage responses and tumor suppression
    Colleen A Brady
    Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Cell 145:571-83. 2011

Research Grants

Detail Information

Publications224 found, 100 shown here

  1. ncbi Mdm2 promotes the rapid degradation of p53
    Y Haupt
    Lautenberg Center for General and Tumor Immunology, The Hebrew University Haddassah Medical School, Jerusalem, Israel
    Nature 387:296-9. 1997
    ..Raised amounts of Mdm2 strongly repress mutant p53 accumulation in tumour-derived cells...
  2. ncbi Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
    M Serrano
    Cold Spring Harbor Laboratory, New York 11724, USA
    Cell 88:593-602. 1997
    ..of primary cells by ras requires either a cooperating oncogene or the inactivation of tumor suppressors such as p53 or p16...
  3. ncbi Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
    L A Donehower
    Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030
    Nature 356:215-21. 1992
    Mutations in the p53 tumour-suppressor gene are the most frequently observed genetic lesions in human cancers...
  4. ncbi Tumor spectrum analysis in p53-mutant mice
    T Jacks
    Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139
    Curr Biol 4:1-7. 1994
    The p53 tumor suppressor gene is mutated in a large percentage of human malignancies, including tumors of the colon, breast, lung and brain. Individuals who inherit one mutant allele of p53 are susceptible to a wide range of tumor types...
  5. ncbi Regulation of p53 stability by Mdm2
    M H Kubbutat
    ABL Basic Research Program, NCI FCRDC, Frederick, Maryland 21702 1201, USA
    Nature 387:299-303. 1997
    The tumour-suppressor p53 is a short-lived protein that is maintained at low, often undetectable, levels in normal cells...
  6. ncbi Oncogene-induced senescence as an initial barrier in lymphoma development
    Melanie Braig
    Charité Universitätsmedizin Berlin Haematology Oncology, 13353 Berlin, Germany
    Nature 436:660-5. 2005
    ..Here we show that Emicro-N-Ras transgenic mice harbouring targeted heterozygous lesions at the Suv39h1, or the p53 locus for comparison, succumb to invasive T-cell lymphomas that lack expression of Suv39h1 or p53, respectively...
  7. ncbi The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation
    J Momand
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, New Jersey 08544 1014
    Cell 69:1237-45. 1992
    ..phosphoprotein with an apparent molecular mass of 90 kd (p90) that forms a complex with both mutant and wild-type p53 protein has been characterized, purified, and identified...
  8. ncbi p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression
    Tongxiang Lin
    Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0322, USA
    Nat Cell Biol 7:165-71. 2005
    The tumour suppressor p53 becomes activated in response to upstream stress signals, such as DNA damage, and causes cell-cycle arrest or apoptosis...
  9. pmc p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation
    Hongwu Zheng
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 455:1129-33. 2008
    ..secondary GBM subtype evolves from the slow progression of a low-grade disease that classically possesses PDGF and TP53 events...
  10. pmc Distinct p53 transcriptional programs dictate acute DNA-damage responses and tumor suppression
    Colleen A Brady
    Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Cell 145:571-83. 2011
    The molecular basis for p53-mediated tumor suppression remains unclear. Here, to elucidate mechanisms of p53 tumor suppression, we use knockin mice expressing an allelic series of p53 transcriptional activation mutants...
  11. ncbi A model for p53-induced apoptosis
    K Polyak
    The Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Nature 389:300-5. 1997
    The inactivation of the p53 gene in a large proportion of human cancers has inspired an intense search for the encoded protein's physiological and biological properties...
  12. pmc Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas
    Wen Xue
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Nature 445:656-60. 2007
    ..b>p53 is an important tumour suppressor that acts to restrict proliferation in response to DNA damage or deregulation of ..
  13. pmc 53BP1 promotes non-homologous end joining of telomeres by increasing chromatin mobility
    Nadya Dimitrova
    The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA
    Nature 456:524-8. 2008
    ....
  14. ncbi Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice
    S E Artandi
    Department of Adult Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nature 406:641-5. 2000
    ..Here we provide evidence that telomere attrition in ageing telomerase-deficient p53 mutant mice promotes the development of epithelial cancers by a process of fusion-bridge breakage that leads to the ..
  15. ncbi Restoration of p53 function leads to tumour regression in vivo
    Andrea Ventura
    Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    Nature 445:661-5. 2007
    ..Although loss of p53 function is a common feature of human cancers, it is not known whether sustained inactivation of this or other ..
  16. pmc Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors
    Jason I Herschkowitz
    Lineberger Comprehensive Cancer Center
    Genome Biol 8:R76. 2007
    ..To address this need, we characterized mammary tumor gene expression profiles from 13 different murine models using DNA microarrays and compared the resulting data to those from human breast tumors...
  17. ncbi Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice
    Sunil R Hingorani
    Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Cancer Cell 7:469-83. 2005
    ..requirements for pancreatic ductal adenocarcinoma (PDA), we have targeted concomitant endogenous expression of Trp53(R172H) and Kras(G12D) to the mouse pancreas, revealing the cooperative development of invasive and widely ..
  18. ncbi Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome
    Kenneth P Olive
    Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 119:847-60. 2004
    ..is commonly altered in human tumors, predominantly through missense mutations that result in accumulation of mutant p53 protein. These mutations may confer dominant-negative or gain-of-function properties to p53...
  19. ncbi Delayed ageing through damage protection by the Arf/p53 pathway
    Ander Matheu
    Tumor Suppression Group, Spanish National Cancer Research Centre CNIO, Madrid 28029, Spain
    Nature 448:375-9. 2007
    ..pathway formed by the alternative reading frame protein of the Cdkn2a locus (Arf) and by p53 (also called Trp53) plays a central part in the detection and elimination of cellular damage, and this constitutes the basis of its ..
  20. pmc mdm2 expression is induced by wild type p53 activity
    Y Barak
    Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel
    EMBO J 12:461-8. 1993
    We have recently characterized a 95 kDa protein, p95, which exhibits enhanced binding to temperature-sensitive p53 (ts-p53) when cells are shifted down to 32...
  21. ncbi High-frequency developmental abnormalities in p53-deficient mice
    J F Armstrong
    Department of Pathology, University Medical School, Edinburgh, UK
    Curr Biol 5:931-6. 1995
    Several strains of mice carrying null mutations of the tumour suppressor gene p53 have been developed. It has been reported that homozygous mice from all of these strains develop normally to birth, but then succumb rapidly to neoplasia.
  22. ncbi Gain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome
    Gene A Lang
    Department of Molecular Genetics, Section of Cancer Genetics, The University of Texas MD Anderson Cancer Center and The University of Texas Graduate School of Biomedical Sciences, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Cell 119:861-72. 2004
    Individuals with Li-Fraumeni syndrome carry inherited mutations in the p53 tumor suppressor gene and are predisposed to tumor development...
  23. pmc Chronic cisplatin treatment promotes enhanced damage repair and tumor progression in a mouse model of lung cancer
    Trudy G Oliver
    David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, 02139, USA
    Genes Dev 24:837-52. 2010
    ..Importantly, we demonstrate that this response does not depend on the tumor suppressor p53 or its transcriptional target, p21...
  24. ncbi p53, the cellular gatekeeper for growth and division
    A J Levine
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, New Jersey 08544, USA
    Cell 88:323-31. 1997
  25. ncbi p53 mutant mice that display early ageing-associated phenotypes
    Stuart D Tyner
    Cell and Molecular Biology Program, Baylor College of Medicine, Houston, TX 77030, USA
    Nature 415:45-53. 2002
    The p53 tumour suppressor is activated by numerous stressors to induce apoptosis, cell cycle arrest, or senescence...
  26. ncbi The differential effects of mutant p53 alleles on advanced murine lung cancer
    Erica L Jackson
    Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02141, USA
    Cancer Res 65:10280-8. 2005
    ..In contrast to the lung tumors, expression of the point-mutant p53 alleles strongly promoted the development of sinonasal adenocarcinomas compared with simple loss-of-function, ..
  27. pmc Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation
    Ssang Taek Lim
    Department of Reproductive Medicine, Moores Cancer Center, University of California, San Diego, 3855 Health Sciences Drive, MC0803, La Jolla, CA 92093, USA
    Mol Cell 29:9-22. 2008
    ..Here we show that, during mouse development, FAK inactivation results in p53- and p21-dependent mesodermal cell growth arrest...
  28. pmc Early inactivation of p53 tumor suppressor gene cooperating with NF1 loss induces malignant astrocytoma
    Yuan Zhu
    Center for Developmental Biology and Kent Waldrep Foundation Center for Basic Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Cancer Cell 8:119-30. 2005
    ..prevalent primary brain tumor, is resistant to all known therapies and frequently harbors mutations that inactivate p53 and activate Ras signaling...
  29. ncbi Nucleolar protein NPM interacts with HDM2 and protects tumor suppressor protein p53 from HDM2-mediated degradation
    Sari Kurki
    Haartman Institute and Molecular Cancer Biology Research Program, Biomedicum Helsinki, University of Helsinki, P O Box 63, FIN 00014 Helsinki, Helsinki, Finland
    Cancer Cell 5:465-75. 2004
    ..an abundant nucleolar phosphoprotein involved in ribosome biogenesis, and interacts with tumor suppressor proteins p53 and Rb...
  30. ncbi p53 suppresses the self-renewal of adult neural stem cells
    Konstantinos Meletis
    Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, SE 171 77 Stockholm, Sweden
    Development 133:363-9. 2006
    ..We show here that the prototypical tumor suppressor p53, which plays an important role in brain tumor initiation and growth, is expressed in the neural stem cell ..
  31. ncbi A subset of p53-deficient embryos exhibit exencephaly
    V P Sah
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Nat Genet 10:175-80. 1995
    ..Mice lacking the p53 tumour suppressor gene are predisposed to tumours, but the viability of these animals indicates that p53 function ..
  32. pmc Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2
    T Kamijo
    Howard Hughes Medical Institute, St Jude Children s Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA
    Proc Natl Acad Sci U S A 95:8292-7. 1998
    ..p16(INK4a) and p19(ARF), that restrain cell growth by affecting the functions of the retinoblastoma protein and p53, respectively...
  33. pmc Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint
    Q Liu
    Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA
    Genes Dev 14:1448-59. 2000
    ..Taken together, these data indicate that Chk1 plays an essential role in the mammalian DNA damage checkpoint, embryonic development, and tumor suppression, and that Atr regulates Chk1...
  34. ncbi Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53
    R Montes de Oca Luna
    Department of Molecular Genetics, University of Texas, M D Anderson Cancer Center, Houston 77030, USA
    Nature 378:203-6. 1995
    The gene p53 encodes a transcriptional activator of genes involved in growth arrest, DNA repair and apoptosis. Loss of p53 function contributes to tumour development in vivo...
  35. ncbi Somatic activation of the K-ras oncogene causes early onset lung cancer in mice
    L Johnson
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Nature 410:1111-6. 2001
    ..This model was further characterized by examining the effects of germline mutations in the tumour suppressor gene p53, which is known to be mutated along with K-ras in human tumours...
  36. ncbi A spatially and temporally restricted mouse model of soft tissue sarcoma
    David G Kirsch
    Center for Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    Nat Med 13:992-7. 2007
    ..Intramuscular delivery of an adenovirus expressing Cre recombinase in mice with conditional mutations in Kras and Trp53 was sufficient to initiate high-grade sarcomas with myofibroblastic differentiation...
  37. doi 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
    ..Here, we report the functional consequences of the simultaneous elimination of Trp53 and retinoblastoma (Rb) genes in epidermis using Cre-loxP system...
  38. ncbi Loss of p53 induces changes in the behavior of subventricular zone cells: implication for the genesis of glial tumors
    Sara Gil-Perotin
    Department Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    J Neurosci 26:1107-16. 2006
    ..This study addresses these questions in mice carrying the deletion of p53, a tumor-suppressor gene expressed in the SVZ...
  39. ncbi Apoptosis in small intestinal epithelial from p53-null mice: evidence for a delayed, p53-independent G2/M-associated cell death after gamma-irradiation
    A J Merritt
    Cancer Research Campaign Department of Epithelial Biology, Christie Hospital Trust, School of Biological Sciences, The University of Manchester, UK
    Oncogene 14:2759-66. 1997
    ..cells has been characterized and quantitated after irradiation of mice rendered homozygously null for the p53 gene. In wild-type animals homozygous for p53 a rapid (4...
  40. pmc Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis
    C M Eischen
    Department of Biochemistry, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Genes Dev 13:2658-69. 1999
    ..The protracted latent period before the onset of frank disease likely reflects the ability of c-Myc to induce a p53-dependent apoptotic program that initially protects animals against tumor formation but is disabled when overtly ..
  41. ncbi Medulloblastoma growth inhibition by hedgehog pathway blockade
    David M Berman
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Science 297:1559-61. 2002
    ....
  42. ncbi Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence
    Akinori Takaoka
    Department of Immunology, Faculty of Medicine and Graduate School of Medicine, University of Tokyo, Hongo 7 3 1, Bunkyo ku, Tokyo 113 0033, Japan
    Nature 424:516-23. 2003
    ..The tumour suppressor p53 and interferon-alpha and -beta (IFN-alpha/beta) are essential for the induction of apoptosis in cancerous cells and ..
  43. ncbi Deregulation of DNA methyltransferases and loss of parental methylation at the insulin-like growth factor II (Igf2)/H19 loci in p53 knockout mice prior to tumor development
    In Young Park
    Department of Biological Sciences, 373 1 Gusung Dong, Korea Advanced Institute of Science and Technology, Yusung Gu, Taejon 305 701, Republic of Korea
    J Cell Biochem 94:585-96. 2005
    To ascertain whether p53 deficiency in vivo leads to the deregulation of DNA methylation machinery prior to tumor development, we investigated the expression profile of DNA methyltransferases in the thymus and the liver of p53(+/+), p53(+..
  44. ncbi DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletion
    Giulia B Celli
    Laboratory for Cell Biology and Genetic, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Nat Cell Biol 7:712-8. 2005
    ..Upon removal of TRF2 from TRF2(F/-) p53-/- mouse embryo fibroblasts, a telomere damage response is observed at most chromosome ends...
  45. pmc p53 regulates metanephric development
    Zubaida Saifudeen
    Section of Pediatric Nephrology, Department of Pediatrics, and the Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, LA 70112, USA
    J Am Soc Nephrol 20:2328-37. 2009
    b>p53 is best known as a tumor suppressor that regulates cell-cycle, differentiation, and apoptosis pathways, but its potential role in embryonic development and organogenesis remains controversial...
  46. pmc A genomewide study identifies the Wnt signaling pathway as a major target of p53 in murine embryonic stem cells
    Kyoung Hwa Lee
    Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 107:69-74. 2010
    Both p53 and the Wnt signaling pathway play important roles in regulating the differentiation of mouse embryonic stem cells (mESCs). However, it is not known whether they directly and/or functionally crosstalk in mESCs...
  47. pmc Evidence for type II cells as cells of origin of K-Ras-induced distal lung adenocarcinoma
    Xia Xu
    Department of Surgery, Duke University, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 109:4910-5. 2012
    ..However, only type II cells appear to progress to adenocarcinoma...
  48. pmc EMT and induction of miR-21 mediate metastasis development in Trp53-deficient tumours
    Olga Bornachea
    Molecular Oncology Unit, CIEMAT, Ave Complutense 40, E 28040 Madrid, Spain
    Sci Rep 2:434. 2012
    ..Here we show that squamous cell carcinomas generated by the specific ablation of Trp53 gene in mouse epidermis are highly metastatic...
  49. pmc Retention of wild-type p53 in tumors from p53 heterozygous mice: reduction of p53 dosage can promote cancer formation
    S Venkatachalam
    Division of Molecular Virology and Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA
    EMBO J 17:4657-67. 1998
    ..The tumor suppressor gene, p53, is mutated in approximately 50% of human sporadic cancers and in an inherited cancer predisposition (Li-Fraumeni ..
  50. pmc The non-apoptotic role of p53 in neuronal biology: enlightening the dark side of the moon
    Andrea Tedeschi
    Laboratory for NeuroRegeneration and Repair, Department of Neurology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Otfried Mueller Strasse 27, Tuebingen D 72076, Germany
    EMBO Rep 10:576-83. 2009
    The transcription factor p53 protects neurons from transformation and DNA damage through the induction of cell-cycle arrest, DNA repair and apoptosis in a range of in vitro and in vivo conditions...
  51. pmc Asymmetry-defective oligodendrocyte progenitors are glioma precursors
    Sista Sugiarto
    Department of Neurological Surgery, University of California San Francisco, USA
    Cancer Cell 20:328-40. 2011
    ..Regulators of asymmetric cell division are misexpressed in low-grade oligodendrogliomas. Our results identify loss of asymmetric division associated with the neoplastic transformation of OPC...
  52. pmc Multiple stress signals activate mutant p53 in vivo
    Young Ah Suh
    Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Res 71:7168-75. 2011
    ..the upstream signals that regulate wild-type p53 are known; however, limited information for the regulation of mutant p53 exists...
  53. ncbi WAF1, a potential mediator of p53 tumor suppression
    W S El-Deiry
    Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231
    Cell 75:817-25. 1993
    ..hybridization approach, we identified a gene, named WAF1, whose induction was associated with wild-type but not mutant p53 gene expression in a human brain tumor cell line. The WAF1 gene was localized to chromosome 6p21...
  54. pmc No requirement for V(D)J recombination in p53-deficient thymic lymphoma
    M J Liao
    Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill Medical School, Chapel Hill, North Carolina 27599, USA
    Mol Cell Biol 18:3495-501. 1998
    The p53 tumor suppressor is activated in response to a variety of cellular stress signals, although specific in vivo signals that trigger tumor suppression are unknown...
  55. pmc Tumorigenesis in mice carrying a truncating Brca1 mutation
    T Ludwig
    Department of Anatomy and Cell Biology, Columbia University, New York, New York 10032, USA
    Genes Dev 15:1188-93. 2001
    ..The mammary tumors showed striking variability in histopathological patterns suggesting stochastic engagement of tumorigenic pathways in their progression, to which the Brca1(tr/tr) mutation was apparently a late participant...
  56. ncbi Reversal of senescence in mouse fibroblasts through lentiviral suppression of p53
    Annette M G Dirac
    Division of Molecular Carcinogenesis, and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    J Biol Chem 278:11731-4. 2003
    ..In mouse embryo fibroblasts (MEFs), induction of senescence requires the presence of p19(ARF) and p53, as genetic ablation of either of these genes allows escape from senescence and leads to immortalization...
  57. pmc Combinations of genetic mutations in the adult neural stem cell compartment determine brain tumour phenotypes
    Thomas S Jacques
    Neural Development Unit, UCL Institute of Child Health and Department of Histopathology, Great Ormond Street Hospital, London, UK
    EMBO J 29:222-35. 2010
    ..We deleted Rb/p53, Rb/p53/PTEN or PTEN/p53 in adult subventricular stem cells; in ectopically neurografted stem cells; in mature ..
  58. pmc p53-dependent senescence delays Emu-myc-induced B-cell lymphomagenesis
    S M Post
    Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Oncogene 29:1260-9. 2010
    The effect of p53-dependent cell-cycle arrest and senescence on Emu-myc-induced B-cell lymphoma development remains controversial...
  59. pmc Calorie restriction delays spontaneous tumorigenesis in p53-knockout transgenic mice
    S D Hursting
    Laboratory of Nutritional and Molecular Regulation, National Cancer Institute Frederick Cancer Research and Development Center, MD 21702
    Proc Natl Acad Sci U S A 91:7036-40. 1994
    Transgenic mice with both alleles of the p53 tumor suppressor gene (frequently mutated in human tumors) knocked out by gene targeting provide a potentially useful tumorigenesis model because these mice rapidly develop spontaneous tumors...
  60. ncbi p53 protein stability in tumour cells is not determined by mutation but is dependent on Mdm2 binding
    C A Midgley
    Department of Biochemistry, University of Dundee, UK
    Oncogene 15:1179-89. 1997
    ..b>Mutant p53 proteins are however frequently detected at constitutively high levels in many tumours and tumour cell lines, ..
  61. ncbi A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy
    Clemens A Schmitt
    Cold Spring Harbor Laboratory, 1 Bungtown Road, New York 11724, USA
    Cell 109:335-46. 2002
    b>p53 and INK4a/ARF mutations promote tumorigenesis and drug resistance, in part, by disabling apoptosis. We show that primary murine lymphomas also respond to chemotherapy by engaging a senescence program controlled by p53 and p16(INK4a)...
  62. ncbi Nutrient availability regulates SIRT1 through a forkhead-dependent pathway
    Shino Nemoto
    Cardiovascular Branch, National Heart, Lung, and Blood Institute NHLBI, Bethesda, MD 20892, USA
    Science 306:2105-8. 2004
    ..Stimulation of SIRT1 transcription by Foxo3a was mediated through two p53 binding sites present in the SIRT1 promoter, and a nutrient-sensitive physical interaction was observed between ..
  63. pmc BH3-only proteins Puma and Bim are rate-limiting for gamma-radiation- and glucocorticoid-induced apoptosis of lymphoid cells in vivo
    Miriam Erlacher
    Division of Experimental Pathophysiology and Immunology, Biocenter, Innsbruck Medical University, A 6020 Innsbruck, Austria
    Blood 106:4131-8. 2005
    Numerous p53 target genes have been implicated in DNA damage-induced apoptosis signaling, but proapoptotic Bcl-2 (B-cell leukemia 2) family members of the BH3 (Bcl-2 homolog region [BH] 3)-only subgroup appear to play the critical ..
  64. pmc 53BP1 cooperates with p53 and functions as a haploinsufficient tumor suppressor in mice
    Irene M Ward
    Division of Oncology Research, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA
    Mol Cell Biol 25:10079-86. 2005
    b>p53 binding protein 1 (53BP1) is a putative DNA damage sensor that accumulates at sites of double-strand breaks (DSBs) in a manner dependent on histone H2AX...
  65. pmc Formation of dynamic gamma-H2AX domains along broken DNA strands is distinctly regulated by ATM and MDC1 and dependent upon H2AX densities in chromatin
    Velibor Savic
    Cell and Molecular Biology Graduate Program, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Mol Cell 34:298-310. 2009
    ..Our data suggest that H2AX fuels a gamma-H2AX self-reinforcing mechanism that retains MDC1 and activated ATM in chromatin near DSBs and promotes continued local phosphorylation of H2AX...
  66. pmc Tissue regenerative delays and synthetic lethality in adult mice after combined deletion of Atr and Trp53
    Yaroslava Ruzankina
    Abramson Family Cancer Research Institute, Department of Cancer Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Nat Genet 41:1144-9. 2009
    b>Trp53 loss of function has previously been shown to rescue tissue maintenance and developmental defects resulting from DNA damage or DNA-repair gene mutations...
  67. pmc Non-stem cell origin for oligodendroglioma
    Anders I Persson
    Department of Neurology, University of California, San Francisco, 94158, USA
    Cancer Cell 18:669-82. 2010
    ..Our results suggest that oligodendroglioma cells show hallmarks of OPCs, and that a progenitor rather than a NSC origin underlies improved prognosis in patients with this tumor...
  68. pmc The requirement of p53 for maintaining chromosomal stability during tetraploidization
    Chui Chui Ho
    Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong
    Oncotarget 1:583-95. 2010
    ..Due to the unequal segregation of chromosomes during multipolar mitosis, the majority of cells were eliminated by p53-dependent mechanisms after tetraploidization...
  69. pmc Deletion of p37Ing1 in mice reveals a p53-independent role for Ing1 in the suppression of cell proliferation, apoptosis, and tumorigenesis
    Andrew H Coles
    Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
    Cancer Res 67:2054-61. 2007
    ..of the inhibitor of growth family, encodes p37(Ing1), a plant homeodomain (PHD) protein that interacts with the p53 tumor suppressor protein and seems to be a critical cofactor in p53-mediated regulation of cell growth and ..
  70. pmc ARF functions as a melanoma tumor suppressor by inducing p53-independent senescence
    Linan Ha
    Laboratory of Cancer Biology and Genetics, National Cancer Institute, Bethesda, MD 20892 4264, USA
    Proc Natl Acad Sci U S A 104:10968-73. 2007
    Inactivation of the p53 pathway represents the most common molecular defect of human cancer...
  71. pmc Loss of p53 causes mitochondrial DNA depletion and altered mitochondrial reactive oxygen species homeostasis
    Maria A Lebedeva
    Department of Pathology, Yale University School of Medicine, New Haven, CT 06520 8023, USA
    Biochim Biophys Acta 1787:328-34. 2009
    In addition to its central role in cellular stress signaling, the tumor suppressor p53 modulates mitochondrial respiration through its nuclear transcription factor activity and localizes to mitochondria, where it enhances apoptosis and ..
  72. pmc Expression of mutant p53 proteins implicates a lineage relationship between neural stem cells and malignant astrocytic glioma in a murine model
    Yuan Wang
    Department of Internal Medicine, Division of Molecular Medicine and Genetics, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Cancer Cell 15:514-26. 2009
    ..Our data show that accumulation of a detectable level of mutant p53 proteins occurs first in neural stem cells in the subventricular zone (SVZ) and that subsequent expansion of ..
  73. pmc Overexpression of Mdm2 in mice reveals a p53-independent role for Mdm2 in tumorigenesis
    S N Jones
    Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Proc Natl Acad Sci U S A 95:15608-12. 1998
    ..Because Mdm2 protein forms a complex with the p53 tumor suppressor protein and down-regulates p53 function, the oncogenic potential of Mdm2 is presumed to be p53-..
  74. pmc Akt activation synergizes with Trp53 loss in oral epithelium to produce a novel mouse model for head and neck squamous cell carcinoma
    Marta Moral
    Division of Biomedicine, Molecular Oncology Unit, CIEMAT, Madrid, Spain
    Cancer Res 69:1099-108. 2009
    ..Here we show that mice displaying constitutive Akt activity (myrAkt) in combination with Trp53 loss in stratified epithelia develop oral cavity tumors that phenocopy human HNSCC...
  75. ncbi p53 regulates mitochondrial respiration
    Satoaki Matoba
    Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Science 312:1650-3. 2006
    ..Here, we show that p53, one of the most frequently mutated genes in cancers, modulates the balance between the utilization of respiratory ..
  76. 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
    Pathways mediated by p53 and Rb are frequently altered in aggressive human cancers, including prostate carcinoma...
  77. ncbi In vitro growth characteristics of embryo fibroblasts isolated from p53-deficient mice
    M Harvey
    Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030
    Oncogene 8:2457-67. 1993
    Fibroblast cultures were derived from mouse embryos containing either one (p53+/-) or two (p53-/-) inactivated p53 alleles and compared to normal embryo fibroblasts for a number of growth parameters...
  78. pmc INK4a/ARF mutations accelerate lymphomagenesis and promote chemoresistance by disabling p53
    C A Schmitt
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Genes Dev 13:2670-7. 1999
    The INK4a/ARF locus encodes upstream regulators of the retinoblastoma and p53 tumor suppressor gene products...
  79. ncbi Negative control of p53 by Sir2alpha promotes cell survival under stress
    J Luo
    Institute of Cancer Genetics and Department of Pathology, College of Physicians and Surgeons, Columbia University, 1150 St Nicholas Avenue, New York, NY 10032, USA
    Cell 107:137-48. 2001
    ..Here, we show that mammalian Sir2alpha physically interacts with p53 and attenuates p53-mediated functions...
  80. pmc The C-terminal lysines fine-tune P53 stress responses in a mouse model but are not required for stability control or transactivation
    Kurt A Krummel
    The Salk Institute for Biological Studies, Gene Expression Laboratory, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 102:10188-93. 2005
    b>P53 is an unstable transcription factor that is mutated in a majority of human cancers...
  81. pmc Chromatin-bound p53 anchors activated Smads and the mSin3A corepressor to confer transforming-growth-factor-beta-mediated transcription repression
    Deepti Srinivas Wilkinson
    Department of Biochemistry and Molecular Biology, Unit 1000, University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
    Mol Cell Biol 28:1988-98. 2008
    In hepatic cells, Smad and SnoN proteins converge with p53 to repress transcription of AFP, an oncodevelopmental tumor marker aberrantly reactivated in hepatoma cells...
  82. pmc p53-targeted LSD1 functions in repression of chromatin structure and transcription in vivo
    Wen Wei Tsai
    Dept of Biochemistry and Molecular Biology, University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Box 1000, Houston, TX 77030, USA
    Mol Cell Biol 28:5139-46. 2008
    Despite years of study focused on the tumor suppressor p53, little is understood about its functions in normal, differentiated cells...
  83. doi p53 regulates the self-renewal and differentiation of neural precursors
    A Armesilla-Diaz
    Department of Cellular and Molecular Physiopathology, Consejo Superior de Investigaciones Cientificas, Ramiro de Maeztu, 9, 28040 Madrid, Spain
    Neuroscience 158:1378-89. 2009
    ..In the present work we report that the absence of tumor suppressor protein p53 increases the number of neurosphere-forming cells and the proliferation of stem cells derived from 13...
  84. pmc Phosphorylation of p53 by IkappaB kinase 2 promotes its degradation by beta-TrCP
    Yifeng Xia
    Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 106:2629-34. 2009
    Functional inactivation of p53 and constitutive activation of the NF-kappaB pathway has been associated with several human cancers...
  85. pmc Loss of p53 enhances catalytic activity of IKKbeta through O-linked beta-N-acetyl glucosamine modification
    Keiko Kawauchi
    Department of Molecular Oncology, Institute of Gerontology, Nippon Medical School, Kawasaki, Kanagawa 211 8533, Japan
    Proc Natl Acad Sci U S A 106:3431-6. 2009
    The IkappaB kinase (IKK)-NF-kappaB pathway plays a critical role in oncogenesis. Recently, we have shown that p53 regulates glucose metabolism through the IKK-NF-kappaB pathway and that, in the absence of p53, the positive feedback loop ..
  86. doi p53 Attenuates lipopolysaccharide-induced NF-kappaB activation and acute lung injury
    Gang Liu
    Department of Medicine, University of Alabama at Birmingham, AL 35294, USA
    J Immunol 182:5063-71. 2009
    The transcriptional factor p53 has primarily been characterized for its central role in the regulation of oncogenesis...
  87. pmc An ARF-independent c-MYC-activated tumor suppression pathway mediated by ribosomal protein-Mdm2 Interaction
    Everardo Macias
    Department of Radiation Oncology, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7512, USA
    Cancer Cell 18:231-43. 2010
    In vitro studies have shown that inhibition of ribosomal biogenesis can activate p53 through ribosomal protein (RP)-mediated suppression of Mdm2 E3 ligase activity...
  88. pmc mdm2 Is critical for inhibition of p53 during lymphopoiesis and the response to ionizing irradiation
    Susan M Mendrysa
    Department of Oncology, School of Medicine Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin 53706, USA
    Mol Cell Biol 23:462-72. 2003
    The function of the p53 tumor suppressor protein must be highly regulated because p53 can cause cell death and prevent tumorigenesis...
  89. pmc Telomere dysfunction suppresses spontaneous tumorigenesis in vivo by initiating p53-dependent cellular senescence
    Wilfredo Cosme-Blanco
    Department of Cancer Genetics, The MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA
    EMBO Rep 8:497-503. 2007
    Dysfunctional telomeres induce p53-dependent cellular senescence and apoptosis, but it is not known which function is more important for tumour suppression in vivo...
  90. ncbi Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53
    S N Jones
    Department of Molecular and Human Genetics, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA
    Nature 378:206-8. 1995
    ..The Mdm2 oncoprotein forms a complex with the p53 tumour-suppressor protein and inhibits p53-mediated transregulation of gene expression...
  91. ncbi Genetic background alters the spectrum of tumors that develop in p53-deficient mice
    M Harvey
    Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030
    FASEB J 7:938-43. 1993
    Using gene targeting in embryonic stem cells, we have generated mice with one or two null p53 germ line alleles...
  92. ncbi Complementary effects of platelet-derived growth factor autocrine stimulation and p53 or Ink4a-Arf deletion in a mouse glioma model
    Göran Hesselager
    Department of Genetics and Pathology, Rudbeck Laboratory, University Hospital, SE 75185 Uppsala, Sweden
    Cancer Res 63:4305-9. 2003
    INK4a-ARF and p53 inactivation are common but rarely concurrent findings in glioblastoma multiforme...
  93. ncbi Modeling the therapeutic efficacy of p53 restoration in tumors
    Carla P Martins
    Cancer Research Institute and Department of Cellular and Molecular Pharmacology, Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA
    Cell 127:1323-34. 2006
    Although restoration of p53 function is an attractive tumor-specific therapeutic strategy, it remains unclear whether p53 loss is required only for transition through early bottlenecks in tumorigenesis or also for maintenance of ..
  94. ncbi The p53-Mdm2 network in progenitor cell expansion during mouse postnatal development
    G Liu
    Department of Cancer Genetics, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    J Pathol 213:360-8. 2007
    Mdm2, an E3 ubiquitin ligase, negatively regulates the tumour suppressor p53. Loss of Mdm2 in mice results in p53-dependent apoptosis and embryonic lethality...
  95. pmc Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function
    Natalie C Jones
    Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA
    Nat Med 14:125-33. 2008
    ..Haploinsufficiency of Tcof1 perturbs mature ribosome biogenesis, resulting in stabilization of p53 and the cyclin G1-mediated cell-cycle arrest that underpins the specificity of neuroepithelial apoptosis and neural ..
  96. doi Caspases and p53 modulate FOXO3A/Id1 signaling during mouse neural stem cell differentiation
    Marcia M Aranha
    iMed UL, University of Lisbon, Portugal
    J Cell Biochem 107:748-58. 2009
    ..p-Akt, p-FOXO3A, and Id1 were significantly reduced throughout differentiation. Caspase-3 processing, p53 phosphorylation, and p53 transcriptional activation increased at 3 days of differentiation, with no evidence of ..
  97. doi Manganese superoxide dismutase versus p53: the mitochondrial center
    Aaron K Holley
    Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40536, USA
    Ann N Y Acad Sci 1201:72-8. 2010
    ..b>p53 is an important tumor suppressing protein that regulates many cellular activities, such as cell cycle regulation, ..
  98. ncbi Tumor suppressor gene expression during normal and pathologic myocardial growth
    K K Kim
    Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis 46202 4800
    J Biol Chem 269:22607-13. 1994
    Previous studies have identified several host proteins (p53, p107, and p193), which form prominent complexes with SV40 T antigen in transformed cardiomyocytes...
  99. pmc Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease
    Carl R Walkley
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Division of Hematology Oncology, Boston, MA 02115, USA
    Genes Dev 22:1662-76. 2008
    ..Analysis of familial cancer syndromes and sporadic cases has strongly implicated both p53 and pRb in its pathogenesis; however, the relative contribution of these mutations to the initiation of ..
  100. pmc Alternatively spliced p53 RNA in transformed and normal cells of different tissue types
    K A Han
    Program of Biochemistry, Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, NY 14263
    Nucleic Acids Res 20:1979-81. 1992
    The alternatively spliced RNA species of tumor suppressor gene p53, containing an additional 96 bases derived from intron 10, is present at approximately 25 to 30% the level of regularly spliced p53 RNA in both normal epidermal and ..
  101. ncbi Temporally distinct patterns of p53-dependent and p53-independent apoptosis during mouse lens development
    H Pan
    Department of Anatomy, University of Wisconsin Medical School, Madison 53706, USA
    Genes Dev 9:2157-69. 1995
    ..The tumor suppressor protein p53 is known to mediate apoptosis induced by the DNA tumor virus oncoproteins, adenovirus E1A (AdE1A) and SV40 T ..

Research Grants62

  1. Transcription Factor P53 in Terminal Nephron Different
    Zubaida Saifudeen; Fiscal Year: 2004
    ..The results of this work will provide information on what determines terminal renal differentiation. In addition, these data will advance our understanding of the role the tumor suppressor p53 in kidney development.
  2. A flexible somatic and sporadic mouse model for pancreatic ductal adenocarcinoma
    Brian Lewis; Fiscal Year: 2007
    ..genetic lesions required for tumor formation, PyMT-encoding retroviruses will be delivered to mice in which the p53 or Ink4a/Arftumor suppressor gene loci, or both, are deleted within the pancreas...
  3. FUNCTION OF NOGGIN IN HAIR FOLLICLE GROWTH AND DISEASE
    Vladimir Botchkarev; Fiscal Year: 2006
    ....
  4. Molecular mediators of metastasis in hepatocellular carcinoma
    Brian C Lewis; Fiscal Year: 2010
    ..recently generated a mouse model for HCC in which lung metastases occur in mice with liver-specific deletion of the p53 and Ink4a/Arftumor suppressor loci, but not in mice with liver-specific deletion of p53 alone...
  5. A ROLE FOR NOGGIN AND BMP2/4 IN HAIR GROWTH CONTROL
    Vladimir Botchkarev; Fiscal Year: 2003
    ..abstract_text> ..
  6. Characterization of Siva in Nervous System Development and Apoptosis
    LAURA ATTARDI; Fiscal Year: 2008
    ..The p53 tumor suppressor is a regulator of cell death known to play a role both in proper neural tube closure and in ..
  7. MOLECULAR MECHANISMS OF CHEMOTHERAPY-INDUCED HAIR LOSS
    Vladimir Botchkarev; Fiscal Year: 2005
    ..Our general strategy is to focus on the p53 transcription factor, which mediates apoptosis and growth arrest induced by chemotherapy and is essential for ..
  8. Apoptotic Mediators in HIV Associated Dementia
    Gwenn Garden; Fiscal Year: 2006
    ..Experiments proposed here will examine how the pro-apoptotic transcription factor p53 promotes neuronal injury or dysfunction in tissue culture and in vivo models of HAD...
  9. The Role of Mdm2 in Lymphoma Development
    CHRISTINE EISCHEN; Fiscal Year: 2007
    unreadable] DESCRIPTION (provided by applicant): Mdm2, an oncoprotein that regulates the tumor suppressor p53, and Myc, an oncoprotein that paradoxically drives both cell cycle progression and apoptosis, are overexpressed in many human ..
  10. 2006 Cancer Model Mechanisms
    William Kaelin; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  11. Ubiquitin, Mitochondrial Stress and AD Pathogenesis
    Zhiqun Tan; Fiscal Year: 2006
    ..Elucidation of the molecular basis of the adverse effects of UPS-mitochondria interactions may contribute to the development of novel pharmacological approaches to treat AD ..
  12. Imaging Kinase Activity In Vivo
    William Weiss; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  13. Precancerous Mammary Transcriptome in Mice after Estrog*
    Teresa Rose Hellekant; Fiscal Year: 2006
    ..Knowing more about cancer molecules will bring more preventive agents quickly to clinical trials. ..
  14. Lung epithelial and vascular morphogenesis
    David Warburton; Fiscal Year: 2006
    ..abstract_text> ..
  15. The role of Hypoxia Inducible Factor-1 alpha in stroke
    David Rempe; Fiscal Year: 2007
    ..3, we will examine the cell type-specific expression of HIF-1 alpha targets as it relates to hypoxic severity and p53 function...
  16. Real-Time Imaging of Hypoxia based on VHL Activity
    William Kaelin; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  17. Olympus FV-1000 Confocal Microscope
    Gwenn Garden; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  18. Novel Functions for Telomerase Enzyme Complex in Vivo
    Steven Artandi; Fiscal Year: 2005
    ..Through analysis of a conditional knockout mouse, we will determine the role of endogenous telomerase in cells in culture and in stern/progenitor compartments in vivo. ..
  19. The Role of Double Strand Breaks in Carcinogenesis
    CHRISTOPHER KEMP; Fiscal Year: 2006
    DESCRIPTION: (PROVIDED BY APPLICANT) The induction of p53 and apoptosis in response to ionizing radiation and other stressors in vivo varies greatly between normal tissues, between cell types within a tissue, and between tumor types...
  20. Bcl-2 family and redox control of genomic instability
    CHARLES KNUDSON; Fiscal Year: 2007
    ..Understanding the pathways that control genomic instability may result in novel therapeutic strategies for the prevention or treatment of lymphoma and other diverse human malignancies. ..
  21. Third International Mdm2 Workshop
    Ute Moll; Fiscal Year: 2005
    ..Scientific Description: The MDM2 protein is the principal negative regulator of the tumor suppressor protein p53. MDM2, a p53-specific E3 ubiquitin lipase, mediates p53 degradation via the 26S proteasome pathway, thus keeping ..
  22. Dendritic Cell-Specific Gene Targeting and Expression
    Boris Reizis; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  23. IGF-1 Signaling & ER crosstalk in mammary cancer in vivo
    Robin Fuchs Young; Fiscal Year: 2008
    ..2) Evaluate the importance of IGF-1 mediated activation of ER signaling (crosstalk) in mammary tumorigenesis and in the development of tamoxifen/antiestrogen resistance in vivo. [unreadable] [unreadable]..
  24. ATM and DNA Damage in the Nervous System
    PETER MCKINNON; Fiscal Year: 2007
    ..abstract_text> ..
  25. STEM CELLS AND AGING
    Stewart Sell; Fiscal Year: 2008
    ..First, the number and homing capacity of bone marrow stem cells from wild type p53+/+ and premature ageing p53+/m C57BL/6J mice will be assayed in vitro and in vivo...
  26. Mutant mouse models of exocrine pancreatic cancer
    DAVID TUVESON; Fiscal Year: 2008
    ..Information gained from this murine model should facilitate further understanding of human pancreatic cancer. ..
  27. 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. ..
  28. AUTOCRINE/PARACRINE GROWTH FACTORS & LUNG MORPHOGENESIS
    David Warburton; Fiscal Year: 2009
    ..Aim 4: To determine the role of tyrosine phosphorylation in protein-protein interaction and supra-molecular assembly of mSPRY2 with SHP2 and FRS2. Aim 5: To determine the functional importance of Shp2 in lung morphogenesis in vivo. ..
  29. Inhibition of Fas-apoptosis in Gastric Cancer
    JeanMarie Houghton; Fiscal Year: 2010
    ..These studies will provide critical insight into novel preventive, and anti-cancer strategies aimed at restoring Fas sensitivity within tumor cells and provide a new direction for cancer treatment. ..
  30. Mechanisms of Lymphocyte Gene Regulation by E2A and Notch1
    BARBARA LYNNE KEE; Fiscal Year: 2010
    ..abstract_text> ..
  31. Role of the Putative Tumor Suppressor PinX1 in the Etiology of Liver Cancer
    Xiao Zhen Zhou; Fiscal Year: 2010
    ..These studies would establish new animal models for studying liver cancer and provide novel insight into the etiology and treatment of liver cancer. ..
  32. Regulation of Nanog in DNA damage response, development and tumorigenesis
    Yang Xu; Fiscal Year: 2010
    ..b>Tumor suppressor p53 is required for this process and suppresses the expression of Nanog by direct binding to its promoter...
  33. Histone Deacetylases and Kidney Development
    Samir S El Dahr; Fiscal Year: 2010
    ..Thus, understanding the epigenetic regulation of kidney development may open new avenues to the treatment or prevention of kidney and urinary tract malformations and kidney failure. ..
  34. HEPTOCYTE PROLIFERATION AND AFLATOXIN METABOLISM
    Stewart Sell; Fiscal Year: 2004
    ..in regard to metabolism of aflatoxin (AFB1) and development of hepatocellular carcinoma (HCC) will be analyzed in p53 null and p53ser246 mutant transgenic, and HBV mice...
  35. AFB1 AND P53 CARCINOGENESIS IN HBSAG TRANSGENIC MICE
    Stewart Sell; Fiscal Year: 2002
    ..and aflatoxin (AFB1) exposure, and these tumors have a high frequency of mutations in the tumor suppressor gene p53 at codon 249 (p53ser249)...
  36. TRANSFORMING GROWTH FACTOR BETA IN OXIDANT LUNG INJURY
    MICHAEL O REILLY; Fiscal Year: 2002
    ..These studies are significant because understanding how ROS injure and kill pulmonary epithelial cells is critically important for improving clinical therapies that rely on supplemental oxygen. ..
  37. CALGB LABORATORY STUDIES IN THE ELDERLY
    William Cance; Fiscal Year: 2002
    ..abstract_text> ..
  38. GENETIC AND HORMONAL MECHANISMS OF BREAST CANCER
    Teresa Rose Hellekant; Fiscal Year: 2002
    ....
  39. CASPASE ENZYMES & APOPTOSIS IN HIV INDUCED NEURAL INJURY
    Gwenn Garden; Fiscal Year: 2003
    ..abstract_text> ..
  40. TRANSGENIC MOUSE MODELS OF PANCREATIC EXOCRINE FUNCTION
    ROBERT DE LISLE; Fiscal Year: 2003
    ..That over expresses Muclin in the pancreatic acinar cell using the rat elastase promoter to direct cell specific expression. ..
  41. PATHOGENEISIS OF CYSTIC FIBROSIS IN THE GI SYSTEM
    ROBERT DE LISLE; Fiscal Year: 2003
    ..Pathology and Muclin expression will be compared in CF mice, and CF mice crossed with gastrin deficient mice (lack gastric acid secretion) to normalize intestinal Ph. ..
  42. CHRONIC HEPATITIS C: MOLECULAR & CELLULAR MARKERS
    Geoffrey Farrell; Fiscal Year: 2003
    ..It will also allow the design of adjunctive treatments more appropriately targeted towards the key pathogenic processes that determine disease progression. ..
  43. Role of Fas/NF kB in H.pylori induced gastric carcinoma
    JeanMarie Houghton; Fiscal Year: 2003
    ..Defining the regulation of these pathways will help define the complex relationship helicobacter shares with its host. ..
  44. Early Events in Colitis-Associated Colorectal Cancer
    Wen Chi Chang; Fiscal Year: 2003
    ..In particular, mutation of the p53 gene appears to be an early event in colitis-associated CRC as is evident from the presence of p53 mutations in the ..
  45. P53 AND MOUSE MAMMARY TUMORIGENESIS
    Daniel Medina; Fiscal Year: 2004
    The p53 tumor suppressor gene is one of the most frequently mutated genes in human breast cancer and includes gain of function mutations as well as deletion mutations...
  46. IR-INDUCED APOPTOSIS IN THE DEVELOPING NERVOUS SYSTEM
    PETER MCKINNON; Fiscal Year: 2004
    ..the analysis of these genes by selecting those that are regulated in wildtype mice, but not in mice such as Atm or p53-null, with defective IR-induced neural apoptosis...
  47. PinX1, a Putative Tumor Suppressor for Prostate Cancer
    Xiao Zhou; Fiscal Year: 2004
    ..Furthermore, these pilot studies are novel and will serve as the first step in obtaining R01 support from NIH to start a new project on prostate cancer. ..
  48. p53-independent Role of MDM2, TGFb Resistance and Cancer
    Peiqing Sun; Fiscal Year: 2006
    ..Our results indicate that an oncogene, mdm2, is a likely cause of TGFbeta resistance through a p53-independent mechanism, most likely by interference with the Rb/3E2F functions...
  49. FUNCTIONAL STUDIES OF IMMUNOGLOBULIN KAPPA ENHANCERS
    Yang Xu; Fiscal Year: 2004
    ..We will again employ genetic approaches to further explore the functions of MiEkappa in somatic hypermutations of Igkappa in a physiological context. ..
  50. GENETICS OF A TRANSGENIC MOUSE MODEL FOR NEUROBLASTOMA
    William Weiss; Fiscal Year: 2004
    ..Given the poor outcome associated with childhood neuroblastoma, this work has the potential to increase our understanding of the pathogenesis of neuroblastoma, and may result in improved therapies for children with this disorder. ..
  51. Excess TGF beta in neonatal lung injury and repair
    David Warburton; Fiscal Year: 2004
    ..abstract_text> ..
  52. APC PATHWAY--A TARGET FOR CHEMOPREVENTIVE INTERVENTION
    Wen Chi Chang; Fiscal Year: 2005
    ..in nutritional biochemistry when combined with the proposed training in cancer prevention and molecular genetics will provide her with the unique ability to develop both natural and synthetic compounds as clinical chemopreventive agents ..
  53. TELOMERE DYSFUNCTION, GENOMIC INSTABILITY AND CANCER
    Steven Artandi; Fiscal Year: 2005
    ..Continued proliferation leads to replicative senescence, a block to continued cell growth. Inactivation of RB and p53 can bypass senescence, allowing further cell division and telomere shortening that triggers crisis, a state of ..
  54. DIFFERENTIATION OF BLOOD STEM CELLS INTO LIVER CELLS
    Stewart Sell; Fiscal Year: 2005
    ..If this project is successful, it would overcome a major hurdle in the possible use of hepatic stem cells for treatment of liver failure or ex vivo gene therapy. ..
  55. 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. ..
  56. Regulation of cell growth and oncogenesis by BcI-2 & Bax
    CHARLES KNUDSON; Fiscal Year: 2005
    ..Our molecular studies will provide insight into the cross talk that occurs between cell death and cell proliferative pathways. ..
  57. Restoration of beta-catenin signaling by perillyl alcoh*
    Wen Chi Chang; Fiscal Year: 2005
    ..Results from the proposed research will determine the feasibility of developing POH as a chemopreventive agent for patients with colorectal cancer and provide the basis for future R01 funding. ..
  58. Modulation of a breast cancer pathway by pregnancy
    Teresa Rose Hellekant; Fiscal Year: 2005
    ..This application has the following specific aims: Aim 1. Develop transgenic mice that permit manipulation of TGFa expression in mammary epithelium. Aim 2. Establish how prior pregnancy affects TGFa -induced mammary tumorigenesis. ..
  59. Melanoma in p16INK4a and p19ARF Deficient Mice
    NORMAN SHARPLESS; Fiscal Year: 2006
    ..Previous work in the mouse, however, shows p19ARF, through its regulation of p53, to be a critical tumor suppressor gene in a wide range of tissues...
  60. PROGESTERONE RECEPTOR IN MYOMETRIUM AND LEIOMYOMA
    Robin Fuchs Young; Fiscal Year: 2002
    ....