tumor suppressor proteins

Summary

Summary: Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.

Top Publications

  1. ncbi Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2
    Thomas G Hofmann
    Division of Immunochemistry G0200 German Cancer Research Center DKFZ, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
    Nat Cell Biol 4:1-10. 2002
  2. ncbi ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage
    Shuhei Matsuoka
    Department of Genetics and Center for Genetics and Genomics, Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Science 316:1160-6. 2007
  3. ncbi DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
    Christopher J Bakkenist
    Department of Hematology Oncology, St Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, Tennessee 38105, USA
    Nature 421:499-506. 2003
  4. ncbi The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate
    T Maehama
    Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109 0606, USA
    J Biol Chem 273:13375-8. 1998
  5. ncbi PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer
    J Li
    Department of Pathology, College of Physicians and Surgeons, Columbia University, 630 West 168 Street, New York, NY 10032, USA
    Science 275:1943-7. 1997
  6. pmc The hippo signaling pathway in development and cancer
    Duojia Pan
    Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Dev Cell 19:491-505. 2010
  7. ncbi TSC2 mediates cellular energy response to control cell growth and survival
    Ken Inoki
    Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
    Cell 115:577-90. 2003
  8. pmc p63 is a suppressor of tumorigenesis and metastasis interacting with mutant p53
    G Melino
    Medical Research Council, Toxicology Unit, Hodgkin Building, Leicester University, Leicester, UK
    Cell Death Differ 18:1487-99. 2011
  9. ncbi DNA double-strand breaks: signaling, repair and the cancer connection
    K K Khanna
    The Queensland Institute of Medical Research, and Department of Pathology, University of Queensland, PO Royal Brisbane Hospital, Brisbane, Queensland, Australia
    Nat Genet 27:247-54. 2001
  10. 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

Detail Information

Publications356 found, 100 shown here

  1. ncbi Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2
    Thomas G Hofmann
    Division of Immunochemistry G0200 German Cancer Research Center DKFZ, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
    Nat Cell Biol 4:1-10. 2002
    ..Interference with HIPK2 expression by antisense oligonucleotides impairs UV-induced apoptosis. Our results imply that HIPK2 is a novel regulator of p53 effector functions involved in cell growth, proliferation and apoptosis...
  2. ncbi ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage
    Shuhei Matsuoka
    Department of Genetics and Center for Genetics and Genomics, Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Science 316:1160-6. 2007
    ..This database paints a much broader landscape for the DDR than was previously appreciated and opens new avenues of investigation into the responses to DNA damage in mammals...
  3. ncbi DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
    Christopher J Bakkenist
    Department of Hematology Oncology, St Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, Tennessee 38105, USA
    Nature 421:499-506. 2003
    ....
  4. ncbi The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate
    T Maehama
    Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109 0606, USA
    J Biol Chem 273:13375-8. 1998
    ..As expected, the C124S mutant of PTEN was incapable of catalyzing dephosphorylation of PtdIns(3,4,5)P3 consistent with the mechanism observed in protein-tyrosine phosphatase-catalyzed reactions...
  5. ncbi PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer
    J Li
    Department of Pathology, College of Physicians and Surgeons, Columbia University, 630 West 168 Street, New York, NY 10032, USA
    Science 275:1943-7. 1997
    ..These homologies suggest that PTEN may suppress tumor cell growth by antagonizing protein tyrosine kinases and may regulate tumor cell invasion and metastasis through interactions at focal adhesions...
  6. pmc The hippo signaling pathway in development and cancer
    Duojia Pan
    Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Dev Cell 19:491-505. 2010
    ..These studies suggest that the core Hippo kinase cascade integrates multiple upstream inputs, enabling dynamic regulation of tissue homeostasis in animal development and physiology...
  7. ncbi TSC2 mediates cellular energy response to control cell growth and survival
    Ken Inoki
    Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
    Cell 115:577-90. 2003
    ..These observations demonstrate a model where TSC2 functions as a key player in regulation of the common mTOR pathway of protein synthesis, cell growth, and viability in response to cellular energy levels...
  8. pmc p63 is a suppressor of tumorigenesis and metastasis interacting with mutant p53
    G Melino
    Medical Research Council, Toxicology Unit, Hodgkin Building, Leicester University, Leicester, UK
    Cell Death Differ 18:1487-99. 2011
    ..This demonstrates an important role for p63 in cancer development and its progression, and the aim of this review is to set this new evidence that links p63 to metastasis within the context of the long conserved other functions of p63...
  9. ncbi DNA double-strand breaks: signaling, repair and the cancer connection
    K K Khanna
    The Queensland Institute of Medical Research, and Department of Pathology, University of Queensland, PO Royal Brisbane Hospital, Brisbane, Queensland, Australia
    Nat Genet 27:247-54. 2001
    ..Moreover, we discuss how tumor suppressor proteins such as p53, ATM, Brca1 and Brca2 have been linked to such pathways, and how accumulating evidence is ..
  10. 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...
  11. ncbi ATM activation by oxidative stress
    Zhi Guo
    Howard Hughes Medical Institute, Department of Molecular Genetics and Microbiology, and Institute for Cellular and Molecular Biology ICMB, University of Texas at Austin, Austin, TX 78712, USA
    Science 330:517-21. 2010
    ..Identification of this pathway explains observations of ATM activation under conditions of oxidative stress and shows that ATM is an important sensor of reactive oxygen species in human cells...
  12. ncbi TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
    Ken Inoki
    Department of Biological Chemistry, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, MI 48109, USA
    Nat Cell Biol 4:648-57. 2002
    ..Our data indicate a molecular mechanism for TSC2 in insulin signalling, tumour suppressor functions and in the inhibition of cell growth...
  13. ncbi Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers
    P A Steck
    Department of Neuro Oncology, University of Texas, M D Anderson Cancer Center, Houston 77030, USA
    Nat Genet 15:356-62. 1997
    ..Our results identify a strong candidate tumour suppressor gene at chromosome 10q23.3, whose loss of function appears to be associated with the oncogenesis of multiple human cancers...
  14. pmc Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands
    J G Herman
    Oncology Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA
    Proc Natl Acad Sci U S A 93:9821-6. 1996
    ....
  15. ncbi Structure, dynamics and functions of promyelocytic leukaemia nuclear bodies
    Rosa Bernardi
    Cancer Genetics Program, Beth Israel Deaconess Cancer Center and Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Nat Rev Mol Cell Biol 8:1006-16. 2007
    ..Recent data suggest that PML-NBs may be heterogeneous in composition, mobility and function...
  16. pmc Loss of p63 and its microRNA-205 target results in enhanced cell migration and metastasis in prostate cancer
    Paola Tucci
    Medical Research Council, Toxicology Unit, Leicester University, Leicester, United Kingdom
    Proc Natl Acad Sci U S A 109:15312-7. 2012
    ..These data suggest that p63/miR-205 may be a useful clinical predictor of metastatic behavior in prostate cancer...
  17. ncbi Estrogen receptor-alpha directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter
    Raphaël Métivier
    European Molecular Biology Laboratory, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Cell 115:751-63. 2003
    ....
  18. ncbi Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN
    V Stambolic
    Amgen Institute, and Department of Medical Biophysics, University of Toronto, Ontario, Canada
    Cell 95:29-39. 1998
    ..Our results show that PTEN may exert its role as a tumor suppressor by negatively regulating the PI3'K/PKB/Akt signaling pathway...
  19. ncbi Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a)
    Utz Herbig
    Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912, USA
    Mol Cell 14:501-13. 2004
    ..Distinct senescence programs can thus progress in parallel, resulting in mosaic cultures as well as individual cells responding to multiple signals...
  20. ncbi Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer
    Martin F Lavin
    Radiation Biology and Oncology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD 4029, Australia
    Nat Rev Mol Cell Biol 9:759-69. 2008
    ....
  21. pmc New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway
    L C Cantley
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 96:4240-5. 1999
    ..PTEN appears to negatively control the phosphoinositide 3-kinase signaling pathway for regulation of cell growth and survival by dephosphorylating the 3 position of phosphoinositides...
  22. ncbi RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation
    Michael H Tatham
    Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    Nat Cell Biol 10:538-46. 2008
    ..These results demonstrate that poly-SUMO chains can act as discrete signals from mono-SUMOylation, in this case targeting a poly-SUMOylated substrate for ubiquitin-mediated proteolysis...
  23. ncbi A Mutant-p53/Smad complex opposes p63 to empower TGFbeta-induced metastasis
    Maddalena Adorno
    Department of Histology, Microbiology and Medical Biotechnologies, University of Padua School of Medicine, viale Colombo 3, 35100 Padua, Italy
    Cell 137:87-98. 2009
    ..Thus, two common oncogenic lesions, mutant-p53 and Ras, selected in early neoplasms to promote growth and survival, also prefigure a cellular set-up with particular metastasis proclivity by TGFbeta-dependent inhibition of p63 function...
  24. ncbi Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1
    Eros Lazzerini Denchi
    Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nature 448:1068-71. 2007
    ..The results reveal how mammalian telomeres use multiple mechanisms to avoid DNA damage surveillance and provide an explanation for the induction of replicative senescence and genome instability by shortened telomeres...
  25. pmc Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG
    Eisuke Itakura
    Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113 8519, Japan
    Mol Biol Cell 19:5360-72. 2008
    ..These results suggest that mammalian cells have at least two distinct class III PI3-kinase complexes, which may function in different membrane trafficking pathways...
  26. ncbi ATM and related protein kinases: safeguarding genome integrity
    Yosef Shiloh
    The David and Inez Myers Laboratory for Genetic Research, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
    Nat Rev Cancer 3:155-68. 2003
    ..Understanding ATM's mode of action provides new insights into the association between defective responses to DNA damage and cancer, and brings us closer to resolving the issue of cancer predisposition in some A-T carriers...
  27. ncbi The tuberous sclerosis complex
    Peter B Crino
    Department of Neurology, University of Pennsylvania Medical Center, Philadelphia 19104, USA
    N Engl J Med 355:1345-56. 2006
  28. ncbi Arsenic degrades PML or PML-RARalpha through a SUMO-triggered RNF4/ubiquitin-mediated pathway
    Valérie Lallemand-Breitenbach
    Université de Paris 7 CNRS UMR 7151, Equipe Labellisée N11 Ligue Nationale Contre le Cancer, Hopital St Louis, 1, Av C Vellefaux 75475 Paris CEDEX 10 France
    Nat Cell Biol 10:547-55. 2008
    ..As PML SUMOylation recruits not only RNF4, ubiquitin and proteasomes, but also many SUMOylated proteins onto PML nuclear bodies, these domains could physically integrate the SUMOylation, ubiquitination and degradation pathways...
  29. ncbi Akt phosphorylates the Yes-associated protein, YAP, to induce interaction with 14-3-3 and attenuation of p73-mediated apoptosis
    Subham Basu
    Signal Transduction, Cancer Research UK London Research Institue, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    Mol Cell 11:11-23. 2003
    ..Akt phosphorylation of YAP may thus suppress the induction of the proapoptotic gene expression response following cellular damage...
  30. pmc Mutant p53 uses p63 as a molecular chaperone to alter gene expression and induce a pro-invasive secretome
    Paul M Neilsen
    Cancer Therapeutics Laboratory, Discipline of Medicine, University of Adelaide, Australia
    Oncotarget 2:1203-17. 2011
    ..Collectively, this study provides mechanistic insight into the complex nature of transcriptional regulation by mutant p53 and implicates a role for tumor-derived p53 mutations in the manipulation of the cancer cell secretome...
  31. ncbi SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27
    A C Carrano
    Department of Pathology, New York University Medical Center, New York 10016, USA
    Nat Cell Biol 1:193-9. 1999
    ..Thus, p27 degradation is subject to dual control by the accumulation of both SKP2 and cyclins following mitogenic stimulation...
  32. ncbi Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG
    Chengyu Liang
    Department of Microbiology and Molecular Genetics and Tumor Virology Division, New England Primate Research Center, Harvard Medical School, 1 Pine Hill Drive, Southborough, MA 01772, USA
    Nat Cell Biol 8:688-99. 2006
    ..These results identify UVRAG as an essential component of the Beclin1-PI(3)KC3 lipid kinase complex that is an important signalling checkpoint for autophagy and tumour-cell growth...
  33. ncbi ATM phosphorylates histone H2AX in response to DNA double-strand breaks
    S Burma
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    J Biol Chem 276:42462-7. 2001
    ..Our results clearly establish ATM as the major kinase involved in the phosphorylation of H2AX and suggest that ATM is one of the earliest kinases to be activated in the cellular response to double-strand breaks...
  34. ncbi Arsenic trioxide controls the fate of the PML-RARalpha oncoprotein by directly binding PML
    Xiao Wei Zhang
    State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China
    Science 328:240-3. 2010
    ..The identification of PML as a direct target of As2O3 provides new insights into the drug's mechanism of action and its specificity for APL...
  35. ncbi Enhanced phosphorylation of p53 by ATM in response to DNA damage
    S Banin
    Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel
    Science 281:1674-7. 1998
    ..Various damage-induced responses may be activated by enhancement of the protein kinase activity of ATM...
  36. ncbi ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin
    Aaron A Goodarzi
    Genome Damage and Stability Centre, University of Sussex, East Sussex BN1 9RQ, UK
    Mol Cell 31:167-77. 2008
    ..These data suggest that the importance of ATM signaling for DSB repair increases as the heterochromatic component of a genome expands...
  37. 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
    ..These results provide in vivo validation for the gain-of-function properties of certain p53 missense mutations and suggest a mechanistic basis for these phenotypes...
  38. ncbi AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1
    R H Medema
    Department of Hematology, University Medical Center, Utrecht, The Netherlands
    Nature 404:782-7. 2000
    ..We conclude that AFX-like proteins are involved in cell-cycle regulation and that inactivation of these proteins is an important step in oncogenic transformation...
  39. pmc The ATM protein kinase and cellular redox signaling: beyond the DNA damage response
    Scott Ditch
    The Howard Hughes Medical Institute, The Department of Molecular Genetics and Microbiology, The University of Texas at Austin, Austin, TX 78712, USA
    Trends Biochem Sci 37:15-22. 2012
    ....
  40. pmc Efficacy of neoadjuvant Cisplatin in triple-negative breast cancer
    Daniel P Silver
    Dana Farber Cancer Institute, Department of Medical Oncology, Smith 209, 1 Jimmy Fund Way, Boston, MA 02115, USA
    J Clin Oncol 28:1145-53. 2010
    ..CONCLUSION Single-agent cisplatin induced response in a subset of patients with TNBC. Decreased BRCA1 expression may identify subsets of TNBCs that are cisplatin sensitive. Other biomarkers show promise in predicting cisplatin response...
  41. pmc ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS
    Angela Alexander
    Department of Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA
    Proc Natl Acad Sci U S A 107:4153-8. 2010
    ....
  42. pmc The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins
    Laura S Harrington
    Cancer Research UK Centre for Cell and Molecular Biology, The Institute of Cancer Research, 237 Fulham Rd, London SW3 6JB, England, UK
    J Cell Biol 166:213-23. 2004
    ..Our results argue that the low malignant potential of tumors arising from TSC1-2 dysfunction may be explained by the failure of TSC mutant cells to activate PI3K and its downstream effectors...
  43. ncbi Regulation of DNA double-strand break repair pathway choice
    Meena Shrivastav
    Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine and Cancer Center, Albuquerque, NM 87131, USA
    Cell Res 18:134-47. 2008
    ....
  44. ncbi Activation of the ATM kinase by ionizing radiation and phosphorylation of p53
    C E Canman
    The Johns Hopkins School of Medicine, Oncology Center, Baltimore, MD 21205, USA
    Science 281:1677-9. 1998
    ..These observations, along with the fact that phosphorylation of p53 on serine-15 in response to ionizing radiation is reduced in ataxia telangiectasia cells, suggest that ATM is a protein kinase that phosphorylates p53 in vivo...
  45. pmc ATM activates the pentose phosphate pathway promoting anti-oxidant defence and DNA repair
    Claudia Cosentino
    Genome Stability Unit, Clare Laboratories, London Research Institute, Cancer Research UK, South Mimms, UK
    EMBO J 30:546-55. 2011
    ..These data suggest that ATM protects cells from ROS accumulation by stimulating NADPH production and promoting the synthesis of nucleotides required for the repair of DSBs...
  46. ncbi Molecular predictors of progression-free and overall survival in patients with newly diagnosed glioblastoma: a prospective translational study of the German Glioma Network
    Michael Weller
    Department of Neurology, University Hospital Zurich, Zurich, Switzerland
    J Clin Oncol 27:5743-50. 2009
    ..The prognostic value of genetic alterations characteristic of glioblastoma in patients treated according to present standards of care is unclear...
  47. ncbi Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage
    Jacob Falck
    The Wellcome Trust and Cancer Research UK Gurdon Institute, and Department of Zoology, Cambridge University, Tennis Court Road, Cambridge CB2 1QN, UK
    Nature 434:605-11. 2005
    ....
  48. pmc PML nuclear bodies
    Valérie Lallemand-Breitenbach
    INSERM CNRS Université Paris Diderot Institut Universitaire Hématologie U944 UMR7212, Laboratoire associé de la Ligue Nationale contre le Cancer, Hopital St Louis, 1, Av C Vellefaux 75475 Paris Cedex 10, France
    Cold Spring Harb Perspect Biol 2:a000661. 2010
    ..Functionally, PML bodies may sequester, modify or degrade partner proteins, but in many ways, PML bodies still constitute an enigma...
  49. ncbi Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine
    J N Sarkaria
    Division of Oncology Research, Mayo Clinic, Rochester, Minnesota 55905, USA
    Cancer Res 59:4375-82. 1999
    ..These data suggest that the radiosensitizing effects of caffeine are related to inhibition of the protein kinase activities of ATM and ATR and that both proteins are relevant targets for the development of novel anticancer agents...
  50. pmc p63 identifies keratinocyte stem cells
    G Pellegrini
    Laboratory of Tissue Engineering IDI, Istituto Dermopatico dell Immacolata, 00040 Rome, Italy
    Proc Natl Acad Sci U S A 98:3156-61. 2001
    ..The identification of p63 as a keratinocyte stem cell marker will be of practical importance for the clinical application of epithelial cultures in cell therapy as well as for studies on epithelial tumorigenesis...
  51. ncbi DNA damage-induced activation of ATM and ATM-dependent signaling pathways
    Ebba U Kurz
    Cancer Biology Research Group, Department of Biochemistry and Molecular Biology, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada
    DNA Repair (Amst) 3:889-900. 2004
    ....
  52. pmc Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella
    G J Pazour
    Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    J Cell Biol 151:709-18. 2000
    ..This indicates that IFT is important for primary cilia assembly in mammals. It is likely that primary cilia have an important function in the kidney and that defects in their assembly can lead to polycystic kidney disease...
  53. pmc Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling
    Ken Inoki
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Genes Dev 17:1829-34. 2003
    ..Our data demonstrate that Rheb acts downstream of TSC1/TSC2 and upstream of mTOR to regulate cell growth...
  54. ncbi Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis
    Megan Cully
    The Campbell Family Institute for Breast Cancer Research, University Health Network, University of Toronto, Toronto, Ontario M5G 2C1, Canada
    Nat Rev Cancer 6:184-92. 2006
    ..How does the PI3K pathway integrate signals from numerous sources, and how can this information be used in the rational design of cancer therapies?..
  55. pmc TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species
    Chong Chen
    Program of Cell and Developmental Biology, Division of Immunotherapy, Department of Surgery, University of Michigan Medical School and Comprehensive Cancer Center, Ann Arbor, MI 48109, USA
    J Exp Med 205:2397-408. 2008
    ..The detrimental effect of up-regulated ROS in metabolically active HSCs may explain the well-documented association between quiescence and the "stemness" of HSCs...
  56. pmc The TSC1-TSC2 complex is required for proper activation of mTOR complex 2
    Jingxiang Huang
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    Mol Cell Biol 28:4104-15. 2008
    ..These data demonstrate that the TSC1-TSC2 complex inhibits mTORC1 and activates mTORC2, which through different mechanisms promotes Akt activation...
  57. ncbi Pten is essential for embryonic development and tumour suppression
    A Di Cristofano
    Department of Human Genetics, Memorial Sloan Kettering Cancer Center, Sloan Kettering Institute, New York, NY 10021, USA
    Nat Genet 19:348-55. 1998
    ..These results support the notion that PTEN haploinsufficiency plays a causal role in CD, LDD and BZS pathogenesis, and demonstrate that Pten is a tumour suppressor essential for embryonic development...
  58. ncbi Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway
    Brendan D Manning
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 10:151-62. 2002
    ..Finally, we find that a tuberin mutant lacking the major PI3K-dependent phosphorylation sites can block the activation of S6K1, suggesting a means by which the PI3K-Akt pathway regulates S6K1 activity...
  59. ncbi Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis
    Gabriella D'Orazi
    Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, Via delle Messi d Oro 156, 00158 Rome, Italy
    Nat Cell Biol 4:11-9. 2002
    ..These data define a new functional interaction between p53 and HIPK2 that results in the targeted subcellular localization of p53 and initiation of apoptosis...
  60. pmc PUMA, a potent killer with or without p53
    J Yu
    Department of Pathology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    Oncogene 27:S71-83. 2008
    ..Therefore, PUMA is a general sensor of cell death stimuli and a promising drug target for cancer therapy and tissue damage...
  61. ncbi Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis
    Li Ma
    Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Cell 121:179-93. 2005
    ..Our findings position the Ras/MAPK pathway upstream of the TSC complex and suggest that Erk may modulate mTOR signaling and contribute to disease progression through phosphorylation and inactivation of TSC2...
  62. pmc PML targeting eradicates quiescent leukaemia-initiating cells
    Keisuke Ito
    Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Department of Medicine, Harvard Medical School, New Research Building, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Nature 453:1072-8. 2008
    ....
  63. pmc Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro
    S Matsuoka
    Howard Hughes Medical Institute, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 97:10389-94. 2000
    ..These results suggest that in vivo, Chk2 is directly phosphorylated by ATM in response to IR and that Chk2 is regulated by phosphorylation of the SCD...
  64. pmc p63 regulates proliferation and differentiation of developmentally mature keratinocytes
    Amy B Truong
    VA Palo Alto Health Care System, Palo Alto, California 94304, USA
    Genes Dev 20:3185-97. 2006
    ..These data indicate that p63 is required for both the proliferative and differentiation potential of developmentally mature keratinocytes...
  65. pmc TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs
    Xiaohua Su
    Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA
    Nature 467:986-90. 2010
    ....
  66. pmc The genetic basis of kidney cancer: a metabolic disease
    W Marston Linehan
    Urologic Oncology Branch, National Cancer Institute, Bethesda, MD 20892 1107, USA
    Nat Rev Urol 7:277-85. 2010
    ..Targeting the fundamental metabolic abnormalities in kidney cancer provides a unique opportunity for the development of more-effective forms of therapy for this disease...
  67. ncbi The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination
    Andrew Kovalenko
    Department of Biological Chemistry, The Weizmann Institute of Science, 76100 Rehovot, Israel
    Nature 424:801-5. 2003
    ..Truncations of CYLD found in cylindromatosis result in reduced enzymatic activity, indicating a link between impaired deubiquitination of CYLD substrates and human pathophysiology...
  68. pmc An early T cell lineage commitment checkpoint dependent on the transcription factor Bcl11b
    Long Li
    Division of Biology 156 29, California Institute of Technology, Pasadena, CA 91125, USA
    Science 329:89-93. 2010
    ....
  69. pmc Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration
    Owen J Sansom
    School of Biosciences, University of Cardiff, Cardiff CF10 3US, Wales
    Genes Dev 18:1385-90. 2004
    ..Critically, for the first time we confirm a series of Wnt target molecules in an in vivo setting and also identify a series of new candidate targets within the same setting...
  70. ncbi Regulation of PTEN transcription by p53
    V Stambolic
    Amgen Research Institute and, Ontario Cancer Institute, 620 University Avenue, Ontario, Toronto, Canada
    Mol Cell 8:317-25. 2001
    ..PTEN was required for p53-mediated apoptosis in immortalized mouse embryonic fibroblasts. Our results reveal a unique role for p53 in regulation of cellular survival and an interesting connection in tumor suppressor signaling...
  71. ncbi CYLD is a deubiquitinating enzyme that negatively regulates NF-kappaB activation by TNFR family members
    Eirini Trompouki
    Institute of Immunology, Biomedical Sciences Research Center Alexander Fleming, 34 Alexander Fleming Street, Vari 16672, Greece
    Nature 424:793-6. 2003
    ..These results indicate that CYLD is a negative regulator of the cytokine-mediated activation of NF-kappaB that is required for appropriate cellular homeostasis of skin appendages...
  72. pmc Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes
    Kaixin Zhou
    Biomedical Research Institute, University of Dundee, Dundee, UK
    Nat Genet 43:117-20. 2011
    ..We conclude that ATM, a gene known to be involved in DNA repair and cell cycle control, plays a role in the effect of metformin upstream of AMP-activated protein kinase, and variation in this gene alters glycemic response to metformin...
  73. ncbi Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association
    J O Lee
    Cellular Biochemistry and Biophysics Program, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Cell 99:323-34. 1999
    ..The phosphatase and C2 domains associate across an extensive interface, suggesting that the C2 domain may serve to productively position the catalytic domain on the membrane...
  74. ncbi Apoptosis and melanoma chemoresistance
    Maria S Soengas
    Department of Dermatology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 28109, USA
    Oncogene 22:3138-51. 2003
    ..With this knowledge in hand, the challenge is now to devise strategies potent enough to compensate or bypass these cell death defects and improve the actual poor prognosis of patients at late stages of the disease...
  75. ncbi Prox1 function is required for the development of the murine lymphatic system
    J T Wigle
    Department of Genetics, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Cell 98:769-78. 1999
    ..These findings suggest that Prox1 is a specific and required regulator of the development of the lymphatic system and that the vascular and lymphatic systems develop independently...
  76. pmc Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks
    Emma Bolderson
    Signal Transduction Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland 4029, Australia
    Nucleic Acids Res 38:1821-31. 2010
    ..These data establish a role for Exo1 in resection of DSBs in human cells, highlighting the critical requirement of Exo1 for DSB repair via HR and thus the maintenance of genomic stability...
  77. pmc PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene
    Nazneen Rahman
    Section of Cancer Genetics, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
    Nat Genet 39:165-7. 2007
    ..i.) = 1.4-3.9, P = 0.0025). The results show that PALB2 is a breast cancer susceptibility gene and further demonstrate the close relationship of the Fanconi anemia-DNA repair pathway and breast cancer predisposition...
  78. ncbi The RASSF1A tumor suppressor
    Howard Donninger
    Molecular Targets Group, Department of Medicine, J G Brown Cancer Center, University of Louisville, 119C Baxter Boulevard, 580 S Preston Street, Louisville, KY 40202, USA
    J Cell Sci 120:3163-72. 2007
    ..Current evidence supports the hypothesis that it serves as a scaffold for the assembly of multiple tumor suppressor complexes and may relay pro-apoptotic signaling by K-Ras...
  79. pmc Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems
    K Podsypanina
    Departments of Pathology and Medicine, College of Physicians and Surgeons, Columbia University, 630 W 168th Street, P and S 14 453, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 96:1563-8. 1999
    ..Taken together, these data suggest that PTEN is a regulator of apoptosis and proliferation that behaves as a "landscaper" tumor suppressor in the gut and a "gatekeeper" tumor suppressor in other organs...
  80. ncbi MGMT promoter methylation in malignant gliomas: ready for personalized medicine?
    Michael Weller
    Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, Zurich, Switzerland
    Nat Rev Neurol 6:39-51. 2010
    ..Moreover, future clinical trials will need to determine, for each subtype of glioma, the degree to which MGMT promoter methylation is predictive or prognostic, and whether testing should become routine clinical practice...
  81. pmc Frequent mutation of BAP1 in metastasizing uveal melanomas
    J William Harbour
    Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO 63110, USA
    Science 330:1410-3. 2010
    ..These findings implicate loss of BAP1 in uveal melanoma metastasis and suggest that the BAP1 pathway may be a valuable therapeutic target...
  82. pmc Prognostic value of three different methods of MGMT promoter methylation analysis in a prospective trial on newly diagnosed glioblastoma
    Arne Christians
    Clinical Cooperation Unit Neuropathology, German Cancer Research Center, DKFZ, Heidelberg, Germany
    PLoS ONE 7:e33449. 2012
    ....
  83. pmc TAp63 induces senescence and suppresses tumorigenesis in vivo
    Xuecui Guo
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
    Nat Cell Biol 11:1451-7. 2009
    ..The ability of TAp63 to trigger senescence and halt tumorigenesis irrespective of p53 status identifies TAp63 as a potential target of anti-cancer therapy for human malignancies with compromised p53...
  84. pmc Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol 3-kinase
    Qiming Sun
    Division of Biochemistry and Molecular Biology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 105:19211-6. 2008
    ....
  85. pmc Interaction between Ras(V12) and scribbled clones induces tumour growth and invasion
    Ming Wu
    Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, 295 Congress Avenue, New Haven, Connecticut 06519, USA
    Nature 463:545-8. 2010
    ..Given the conservation of the pathways examined here, similar cooperative mechanisms could have a role in the development of human cancers...
  86. ncbi The regulation of AMPK beta1, TSC2, and PTEN expression by p53: stress, cell and tissue specificity, and the role of these gene products in modulating the IGF-1-AKT-mTOR pathways
    Zhaohui Feng
    Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey, USA
    Cancer Res 67:3043-53. 2007
    ..Upon glucose starvation of E1A-transformed mouse embryo fibroblasts, a p53-mediated apoptosis ensues. Thus, there is a great deal of communication between the p53 pathway and the IGF-1-AKT and mTOR pathways...
  87. ncbi Gain of function of mutant p53 by coaggregation with multiple tumor suppressors
    Jie Xu
    Switch Laboratory, Flanders Institute for Biotechnology, Vrije Universiteit Brussel, Brussels, Belgium
    Nat Chem Biol 7:285-95. 2011
    ..Overall, our study reveals a novel disease mechanism for mutant p53 gain of function and suggests that, at least in some respects, cancer could be considered an aggregation-associated disease...
  88. ncbi p53-family proteins and their regulators: hubs and spokes in tumor suppression
    L Collavin
    Laboratorio Nazionale CIB, Area Science Park, Trieste, Italy
    Cell Death Differ 17:901-11. 2010
    ....
  89. pmc A complex interplay between Akt, TSC2 and the two mTOR complexes
    Jingxiang Huang
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA
    Biochem Soc Trans 37:217-22. 2009
    ..The present review discusses our current understanding of the increasingly complex functional interactions between Akt, the TSC1-TSC2 complex and mTOR, which are fundamentally important players in a large variety of human diseases...
  90. ncbi PKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest
    Jiyong Liang
    Molecular and Cell Biology, Sunnybrook and Women s College Health Sciences Centre, St Mary s Hospital, McGill University, Montreal, Quebec
    Nat Med 8:1153-60. 2002
    ..Thus, we show a novel mechanism whereby Akt impairs p27 function that is associated with an aggressive phenotype in human breast cancer...
  91. pmc Reversal of learning deficits in a Tsc2+/- mouse model of tuberous sclerosis
    Dan Ehninger
    Department of Neurobiology, Brain Research Institute, University of California, Los Angeles, 695 Charles E Young Drive South, Los Angeles, California 90095, USA
    Nat Med 14:843-8. 2008
    ....
  92. pmc RASSF1A elicits apoptosis through an MST2 pathway directing proapoptotic transcription by the p73 tumor suppressor protein
    David Matallanas
    Signaling and Proteomics Laboratory, The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK
    Mol Cell 27:962-75. 2007
    ..Our results describe an MST2-dependent effector pathway for RASSF1A proapoptotic signaling and indicate that silencing of RASSF1A in tumors removes a proapoptotic signal emanating from p73...
  93. ncbi 53BP1-dependent robust localized KAP-1 phosphorylation is essential for heterochromatic DNA double-strand break repair
    Angela T Noon
    Genome Damage and Stability Centre, University of Sussex, East Sussex, BN1 9RQ, UK
    Nat Cell Biol 12:177-84. 2010
    ..We propose that ionizing-radiation induced foci (IRIF) spatially concentrate ATM activity to promote localized alterations in regions of chromatin otherwise inhibitory to repair...
  94. ncbi The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54
    M Kotani
    Institut de Recherche Interdisciplinare en Biologie Humaine et Nucléaire I R I B H N, Brussels, Belgium
    J Biol Chem 276:34631-6. 2001
    ..Stimulation of oxytocin secretion after kisspeptin administration to rats confirmed this hypothesis...
  95. ncbi The LKB1 tumor suppressor negatively regulates mTOR signaling
    Reuben J Shaw
    Department of Systems Biology, Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA
    Cancer Cell 6:91-9. 2004
    ..These findings position aberrant mTOR activation at the nexus of these germline neoplastic conditions and suggest the use of mTOR inhibitors in the treatment of Peutz-Jeghers syndrome...
  96. ncbi p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest
    G J Hannon
    Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724
    Nature 371:257-61. 1994
    ..The gene encoding p15 is located on chromosome 9 adjacent to the p16 gene at a frequent site of chromosomal abnormality in human tumours (9p21)...
  97. ncbi Role of Mre11 in chromosomal nonhomologous end joining in mammalian cells
    Emilie Rass
    Unité mixte de recherche 217, Centre National de la Recherche Scientifique Commissariat à l Energie Atomique, Equipe labellisée LA LIGUE 2008, Institut de Radiobiologie Cellulaire et Moleculaire, Fontenay aux Roses, France
    Nat Struct Mol Biol 16:819-24. 2009
    ..These data demonstrate that, in addition to its role in ATM activation, Mre11 can favor alternative NHEJ through its nuclease activity...
  98. pmc Ubiquitination regulates PTEN nuclear import and tumor suppression
    Lloyd C Trotman
    Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Cell 128:141-56. 2007
    ....
  99. ncbi RASSF1A interacts with microtubule-associated proteins and modulates microtubule dynamics
    Ashraf Dallol
    Section of Medical and Molecular Genetics, Division of Reproductive and Child Health, University of Birmingham, The Medical School, Edgbaston, Birmingham, United Kingdom
    Cancer Res 64:4112-6. 2004
    ..Our data identify a role for RASSF1A in the regulation of microtubules and cell cycle dynamics that could be part of the mechanism(s) by which RASSF1A exerts its growth inhibition on cancer cells...
  100. ncbi The candidate tumour suppressor p33ING1 cooperates with p53 in cell growth control
    I Garkavtsev
    Department of Medical Biochemistry and Southern Alberta Cancer Research Center, University of Calgary, Canada
    Nature 391:295-8. 1998
    ..These results indicate that p33ING1 is a component of the p53 signalling pathway that cooperates with p53 in the negative regulation of cell proliferation by modulating p53-dependent transcriptional activation...
  101. ncbi Genetic pathways to glioblastoma: a population-based study
    Hiroko Ohgaki
    International Agency for Research on Cancer, Lyon, France
    Cancer Res 64:6892-9. 2004
    ..0208). This suggests that the acquisition of TP53 mutations in these glioblastoma subtypes occurs through different mechanisms...

Research Grants62

  1. Human Papillomavirus Association with Subsets of Colorectal Cancer
    Polly A Newcomb; Fiscal Year: 2010
    ..HPV promotes oncogenesis via viral proteins E6 and E7. These interfere with tumor suppressor proteins p53 and pRb and induce telomerase, thereby immortalizing cells...
  2. Analysis of the Human c-myc Gene Replication Origin
    Michael Leffak; Fiscal Year: 2012
    ..Errors in the components of the multiprotein replication initiation complex, or the inability of tumor suppressor proteins to resolve blocks to fork movement lead to rearrangements, losses or duplications of DNA, and result in ..
  3. POSTDOCTORAL TRAINING IN TUMOR BIOLOGY
    Michael L Cleary; Fiscal Year: 2013
    ..mechanisms in normal and malignant cells;biochemical and molecular actions of oncoproteins and tumor suppressor proteins;tumor immunology and virology;immunogenetics and immunoregulation in human and murine model systems...
  4. Spinocerebellar ataxia 7 protein function.
    Patrick A Grant; Fiscal Year: 2010
    ..HAT proteins are known to associate with cellular oncoproteins and tumor suppressor proteins and have been described in certain translocations associated with leukemias and thus have been ..
  5. The structural role of ING proteins in chromatin remodeling.
    KAREN CHAMPAGNE GLASS; Fiscal Year: 2010
    ..ING3, ING4 and INGS are tumor suppressor proteins involved in controlling the way DNA is packaged within our cells...
  6. ROCK II-mediated regulation of centrosome duplication / centrosome amplification
    Kenji Fukasawa; Fiscal Year: 2013
    ..Mutations of those oncoproteins and tumor suppressor proteins result in numeral abnormality of centrosomes, leading to mitotic defects and consequentially ..
  7. The Control of Centriole Duplication and Degeneration
    Meng Fu Bryan Tsou; Fiscal Year: 2013
    ..For example, centrosome amplification strongly correlates with loss of tumor suppressor proteins (such as p53 and pRB), and is induced after expression of viral oncoproteins (such as adenovirus E1A, ..
  8. SV40 T Antigen Role in Virus Growth and Transformation
    James M Pipas; Fiscal Year: 2010
    ..T antigen drives cells into S phase by inhibiting the Rb-family of tumor suppressor proteins, and thus activating the expression of genes regulated by the E2F-family of transcription factors...
  9. Molecular Analysis and Role of RGS6 as a Novel Growth Suppressor
    Rory A Fisher; Fiscal Year: 2010
    ..Therefore, it is surprising that RGS proteins have not been considered previously as growth or tumor suppressor proteins. Here we provide new evidence suggesting such a role for a member of the RGS protein family, RGS6, which ..
  10. Biology of the Myb-MuvB Oncoprotein Tumor Suppressor Protein Complex
    JOSEPH STEVEN LIPSICK; Fiscal Year: 2013
    ..Previous work has shown that the MuvB tumor suppressor proteins prevent the expression of genes that promote cell division...
  11. Regulation of the Mono-Ubiquitination of the Fanconi Anemia D2 Protein
    NIALL GEORGE HOWLETT; Fiscal Year: 2013
    ..The FA proteins function cooperatively with the tumor suppressor proteins BRCA1 and BRCA2 (FANCD1) in the FA- BRCA pathway to repair damaged DNA and to prevent cellular ..
  12. Cell-cell adhesion and signal transduction
    Valeri Vasioukhin; Fiscal Year: 2012
    ..This knowledge is necessary for development of novel targeted therapies for treatment of skin cancer. ..
  13. Structure and function of the U3 RNA-protein complex
    Carl C Correll; Fiscal Year: 2010
    ....
  14. Expression of Simiam Virus 40 T Antigens in Intestine
    James M Pipas; Fiscal Year: 2013
    ..T antigen acts in part by inhibiting the action of two tumor suppressor proteins, members of the retinoblastoma (Rb) family, and p53...
  15. Tip60 in p38 and PRAK Mediated Oncogene-Induced Senescence and Tumor Suppression
    Peiqing Sun; Fiscal Year: 2012
    ..studies focus on a protein kinase PRAK and an acetyltransferase Tip60, both of which are likely to be tumor suppressor proteins. Results from these studies will define the signal transduction pathway mediating the senescence ..
  16. Transcriptional regulation of oncogenic properties of mutant p53
    Luis Alfonso Martinez; Fiscal Year: 2013
    ..the mutant p53 protein functions as an oncogene: the first involves the physical inactivation of other tumor suppressor proteins such as its family members, p63 and p73, and the other is dependent on its ability to regulate gene ..
  17. Rad50: Roles in chromo. stab. and prev. of malignancy
    JOHN HJ PETRINI; Fiscal Year: 2013
    ..and mice mutants in p53, ATM and PTEN will be examined to test the hypothesis that chromosome instability in Rad50 mutants will increase the penetrance of mutations affecting these tumor suppressor proteins and predispose to cancer.
  18. Cervical Cancer Cofactors and HPV DNA Integration
    Wayne Lancaster; Fiscal Year: 2005
    ..The vast majority of CaCx are associated with high risk HPV types. HPV-16 perturbs the function of the tumor suppressor proteins p53 by HPV E6 and pRB by HPV E7 proteins...
  19. The Role of Beta-catenin/Tcf Pathway Defects in Cancer
    Eric Fearon; Fiscal Year: 2009
    ..kinase 3beta (GSK3beta) protein functions in concert with the Axin and APC (adenomatous polyposis coli) tumor suppressor proteins and other kinases to phosphorylate (-catenin at multiple serine and threonine residues in its amino (N)-..
  20. Anti-cancer effects by the green tea catechins
    SEUNG BAEK; Fiscal Year: 2006
    ..Some reports are suggesting an involvement of p53 tumor suppressor proteins, but others do not...
  21. SV40-LIKE SEQUENCES IN HUMAN TUMORS ANALYSES
    Michele Carbone; Fiscal Year: 2001
    ..if the SV40-like antigen (Tag) produced in human mesotheliomas binds and inactivates the cellular tumor suppressor proteins known to bind Tag in tissue culture: p53, Rb, pRb2, p107, p300...
  22. Investigation of the Function and Regulationof Peroxiredoxins Prdx1 and Prdx6 in
    SHELLEY PHELAN; Fiscal Year: 2009
    ..However, certain members of this family have now been implicated as tumor suppressor proteins. Prdx1 and Prdx6 are two structurally and functionally distinct peroxiredoxins that are overexpressed in ..
  23. How Karyopherins Move Across The Nuclear Pore Complex
    Michael Rexach; Fiscal Year: 2006
    ..b>Tumor suppressor proteins, hormone receptors, and cell-cycle checkpoint control proteins are among the hundreds of essential ..
  24. Molecular mediators of metastasis in hepatocellular carcinoma
    Brian C Lewis; Fiscal Year: 2010
    ..to: 1) Explore whether the induction of metastasis is dependent on the loss of either the p16 or p19 tumor suppressor proteins (encoded by the Ink4a/Arf locus), or both...
  25. Nuclear Function of the c-Abl Protooncoprotien
    Jean Wang; Fiscal Year: 2007
    ..The upstream regulators of c-Abl are two tumor suppressor proteins. The retinoblastoma tumor suppressor (RB) inhibits c-Abl in G0G1 nuclei...
  26. REGULATION OF P130 DURING THE CELL CYCLE AND QUIESCENCE
    Xavier Grana; Fiscal Year: 2000
    ..Although pRb is one of the best characterized tumor suppressor proteins, very little is known about p107 and p130...
  27. Targeted Gene Knockouts of p14ARF and p16INK4a
    Utz Herbig; Fiscal Year: 2005
    ..This locus encodes the two tumor suppressor proteins p16 INK4a and p14 ARF...
  28. MAPPING SURFACE CONTACTS IN BIOMACROMOLECULE COMPLEXES
    Alan Marshall; Fiscal Year: 2000
    ..The INK4 family of tumor suppressor proteins (p15,p16,p18,p19) acts in part by forming non-covalent complexes with cyclin-dependent kinases (cdk, 34-..
  29. IDENTIFICATION AND ANALYSIS OF HAT/COACTIVATOR COMPLEXES
    Patrick Grant; Fiscal Year: 2005
    ..HAT/coactivator proteins are known to associate with cellular oncoproteins and tumor suppressor proteins and have been described in certain translocations associated with leukemias...
  30. The role of Inil in chromatin development and cancer
    Stephen Jones; Fiscal Year: 2006
    ..Subunits of the SWI/SNF enzymes interact with Rb and BRCA-l, known tumor suppressor proteins. The recent identification of Ini1 mutations in familial malignant rhabdoid tumors has further ..
  31. Structural and Functional Analysis of Oxygen Sensor
    Hao Zhu; Fiscal Year: 2003
    ..Hypoxic inducible factors (HIF) and von Hippel-Lindau (VHL) tumor suppressor proteins are so far the only well-characterized proteins in the mammalian oxygen sensing pathway...
  32. Brk interaction with ErbB receptors alters cell fate
    Julie Ostrander; Fiscal Year: 2006
    ..In addition to genetic alterations of tumor suppressor proteins and oncoproteins, enhanced tyrosine kinase activity is also associated with breast cancer and is a ..
  33. EXPRESSION AND FUNCTIONS OF MDM2 PROTEINS
    MARY PERRY; Fiscal Year: 2001
    ..likely to contribute to the development of cancer because MDM2 proteins antagonize the functions of two tumor suppressor proteins, p53 and the retinoblastoma protein...
  34. ROLE OF CHROMATIN REMODELING IN GROWTH CONTROL
    GAVIN SCHNITZLER; Fiscal Year: 2004
    ..might be essential for growth control mechanisms through recruitment by the retinoblastoma family of tumor suppressor proteins. Although this evidence indicates an important role for these complexes, it tells us very little about ..
  35. BIOLOGY OF THE PAPILLOMAVIRUS E5 ONCOPROTEIN FAMILY
    Richard Schlegel; Fiscal Year: 2010
    ..and differentiation, target the p53 and Rb tumor suppressor proteins, and induce the hTERT gene and cellular immortalization...
  36. BRCA1 Function
    Jeffrey Parvin; Fiscal Year: 2006
    DESCRIPTION: (provided by applicant) Breast cancer is associated with the loss of function of tumor suppressor proteins as well as the activation of oncogenes...
  37. SV40 st induced cell transformation via PP2A inhibition
    Madathia Sarkissian; Fiscal Year: 2007
    ..learned much about specific cellular components that regulate the proliferation of cells, such as the tumor suppressor proteins p53 and the retinoblastoma, by deciphering LT and 17K function but relatively little is known about st...
  38. SUMO conjugation in cell biology and Development
    Albert J Courey; Fiscal Year: 2010
    ..Furthermore, the sumoylation of numerous oncoproteins (c-jun, elk-1, and TEL) and tumor suppressor proteins (p53, RB, and PML) modulates their function...
  39. Transduction of Tumor Suppressor Proteins into Gliomas
    STEVEN DOWDY; Fiscal Year: 2005
    ..We propose to test this hypothesis by generating transducible tumor suppressor proteins. My laboratory has further developed the methodology of protein transduction...
  40. The Function of RASSF1A in T Cells
    JOANNE PRATT; Fiscal Year: 2009
    Significant research efforts have focused on the tumor suppressor proteins involved in inhibition of cell cycle progression and induction of programmed cell death in cancer models...
  41. ANALYSIS OF P73 FUNCTION AND REGULATION BY E2F 1
    Meredith Irwin; Fiscal Year: 2001
    Dual inactivation of the retinoblastoma (pRb) and p53 tumor suppressor proteins occurs commonly during carcinogenesis. Inactivation of pRb leads to dysregulation of the E2F transcription factor family...
  42. PROHIBITIN GENE IN GROWTH CONTROL AND TUMOR SUPPRESSION
    Srikumar Chellappan; Fiscal Year: 2009
    ..These events are stringently regulated by a complex machinery comprising of signaling molecules, tumor suppressor proteins, transcription factors and their downstream targets...
  43. MDM2 AND P53 IN TUMOR CELLS
    DONNA GEORGE; Fiscal Year: 2000
    ..Proteins encoded by the mdm2 oncogene can bind to, and inhibit the function of, two key tumor suppressor proteins, p53 and RB. Dr...
  44. Proteolytic Control Of Yeast Cell Type
    JEFFREY LANEY; Fiscal Year: 2009
    ..factors, signaling molecules, cell cycle regulators, apoptotic factors, proto-oncogene products, and tumor suppressor proteins. In eukaryotes, these regulatory proteins are targeted for destruction by a complex enzymatic system ..
  45. G1 Cell Cycle in Tumorigenesis and Senescence
    E Reddy; Fiscal Year: 2007
    ..e. mutant CDK4, E1A and MDM2) and potential tumor suppressor proteins (p130 and p107) alter these critical regulatory pathways. In Project #1, Dr...
  46. Heterogeneity of Human Melanoma, Cytokines and iNOS
    Elizabeth Grimm; Fiscal Year: 2006
    ..Aim II address molecular mechanisms of NO in melanoma, with an initial emphasis on the nitration of tumor suppressor proteins. Preliminary evidence suggests that a functional inactivation of wtp53 may be directly related to ..
  47. Structural-Function Studies of Shared hRNAP Components
    JOHN LADIAS; Fiscal Year: 2005
    ..3) To dissect the role of the common subunits hRPB10alpha, hRPB10beta, and hRPB8 in the function of tumor suppressor proteins. These studies will provide high-resolution three-dimensional structures of the human common subunits ..
  48. Cellular Mechanisms for Tubuloglomerular Feedback
    Phillip Bell; Fiscal Year: 2009
    ..Overall these studies should provide important new information regarding the role of ATP in macula densa signaling, activation of the tubuloglomerular feedback mechanism, and control of glomerular hemodynamics. ..
  49. Regulation of Mdm2 compartmentalization
    Lindsey Mayo; Fiscal Year: 2009
    ....
  50. Melanoma in p16INK4a and p19ARF Deficient Mice
    NORMAN SHARPLESS; Fiscal Year: 2006
    ..Such a model could then serve as a foundation for future studies of melanoma progression and therapy, and the results of this work will have implications for the treatment of human MM. ..
  51. SODIUM-CALCUIM EXCHANGE IN THE RENAL MICROCIRCULATION
    Phillip Bell; Fiscal Year: 2003
    ....
  52. 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. ..
  53. 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. ..
  54. MICROTUBULE/KERATIN INTERACTIONS DURING SPERMATOGENESIS
    ABRAHAM KIERSZENBAUM; Fiscal Year: 2002
    ..Engineering mouse models in which the expression of K9 is null, is important for both reproductive biology and cancer research. ..
  55. IMRT in the Treatment of Node-Positive Breast Cancer
    Lori Pierce; Fiscal Year: 2003
    ..4) Determine the effect of motion on static IMRT and PWTF dose distributions, and then correct/adjust for motion to determine the best delivery-optimized plan. ..
  56. HTLV Deregulation of CD40(L) in Cancer&Neurodegeneration
    Edward Harhaj; Fiscal Year: 2007
    ..Completion of the proposed studies may lead to therapeutic strategies of immune modulation, which could prevent leukemia and/or neuroinflammatory disease. [unreadable] [unreadable] [unreadable] [unreadable]..
  57. PHOSPHOLIPASE C AND CARDIAC HYPERTROPHY
    GERALD DORN; Fiscal Year: 2005
    ..abstract_text> ..
  58. Senescence and Longevity Modulating Genes, WRN and BLM
    Judith Campisi; Fiscal Year: 2008
    ..Our studies will provide important insights into how WRN and BLM postpone the development of aging phenotypes and the development of cancer in humans. ..
  59. Roles of Tuberin (TSC2), Hamartin (TSC1), and Rheb in Renal Cyst Pathogenesis
    Elizabeth P Henske; Fiscal Year: 2010
    ....
  60. DIET AND SOMATIC MUTATIONS IN COLON CANCER
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2007
    ..e. p53, K-ras, and microsatellite instability). Differences in colon and rectal tumors will be compared. Additionally data from rectal tumors will be combined with that from colon tumors to define disease pathways. ..