neurofibromin 2

Summary

Summary: A membrane protein homologous to the ERM (Ezrin-Radixin-Moesin) family of cytoskeleton-associated proteins which regulate physical properties of membranes. Alterations in neurofibromin 2 are the cause of NEUROFIBROMATOSIS 2.

Top Publications

  1. pmc Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus
    Wei Li
    Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cell 140:477-90. 2010
  2. doi Merlin regulates transmembrane receptor accumulation and signaling at the plasma membrane in primary mouse Schwann cells and in human schwannomas
    D Lallemand
    INSERM, U674, Paris, France
    Oncogene 28:854-65. 2009
  3. pmc Loss of tumor suppressor Merlin in advanced breast cancer is due to post-translational regulation
    K Adam Morrow
    Department of Oncologic Sciences, Mitchell Cancer Institute, Mobile, Alabama 36604, USA
    J Biol Chem 286:40376-85. 2011
  4. pmc Contact-dependent inhibition of EGFR signaling by Nf2/Merlin
    Marcello Curto
    MGH Center for Cancer Research, Harvard Medical School Department of Pathology, Charlestown, MA 02129, USA
    J Cell Biol 177:893-903. 2007
  5. pmc The neurofibromatosis 2 protein, merlin, regulates glial cell growth in an ErbB2- and Src-dependent manner
    S Sean Houshmandi
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Mol Cell Biol 29:1472-86. 2009
  6. ncbi Merlin and ERM proteins: unappreciated roles in cancer development?
    Andrea I McClatchey
    Massachusetts General Hospital Cancer Center, Harvard Medical School Department of Pathology, 149 13th Street, Charlestown, Massachusetts 02129, USA
    Nat Rev Cancer 3:877-83. 2003
  7. pmc Erbin and the NF2 tumor suppressor Merlin cooperatively regulate cell-type-specific activation of PAK2 by TGF-beta
    Mark C Wilkes
    Thoracic Diseases Research Unit, Department of Biochemistry and Molecular Biology and Mayo Clinic Cancer Center, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Dev Cell 16:433-44. 2009
  8. pmc The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44
    H Morrison
    Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, and University of Karlsruhe, Institute of Genetics, 76021 Karlsruhe, Germany
    Genes Dev 15:968-80. 2001
  9. pmc The NF2 tumor suppressor gene product, merlin, inhibits cell proliferation and cell cycle progression by repressing cyclin D1 expression
    Guang Hui Xiao
    Human Genetics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    Mol Cell Biol 25:2384-94. 2005
  10. pmc Unfurling of the band 4.1, ezrin, radixin, moesin (FERM) domain of the merlin tumor suppressor
    S D Yogesha
    Cell Adhesion Laboratory, Department of Cancer Biology, The Scripps Research Institute, Jupiter, Florida 33458, USA
    Protein Sci 20:2113-20. 2011

Detail Information

Publications263 found, 100 shown here

  1. pmc Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus
    Wei Li
    Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cell 140:477-90. 2010
    ..We propose that Merlin suppresses tumorigenesis by translocating to the nucleus to inhibit CRL4(DCAF1)...
  2. doi Merlin regulates transmembrane receptor accumulation and signaling at the plasma membrane in primary mouse Schwann cells and in human schwannomas
    D Lallemand
    INSERM, U674, Paris, France
    Oncogene 28:854-65. 2009
    ....
  3. pmc Loss of tumor suppressor Merlin in advanced breast cancer is due to post-translational regulation
    K Adam Morrow
    Department of Oncologic Sciences, Mitchell Cancer Institute, Mobile, Alabama 36604, USA
    J Biol Chem 286:40376-85. 2011
    ....
  4. pmc Contact-dependent inhibition of EGFR signaling by Nf2/Merlin
    Marcello Curto
    MGH Center for Cancer Research, Harvard Medical School Department of Pathology, Charlestown, MA 02129, USA
    J Cell Biol 177:893-903. 2007
    ..These studies define a new mechanism of tumor suppression, provide mechanistic insight into the poorly understood phenomenon of contact-dependent inhibition of proliferation, and suggest a therapeutic strategy for NF2-mutant tumors...
  5. pmc The neurofibromatosis 2 protein, merlin, regulates glial cell growth in an ErbB2- and Src-dependent manner
    S Sean Houshmandi
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Mol Cell Biol 29:1472-86. 2009
    ..Lastly, we show that merlin competes with Src for direct binding to ErbB2 and present a novel molecular mechanism for merlin regulation of ErbB2-dependent Src signaling and growth control...
  6. ncbi Merlin and ERM proteins: unappreciated roles in cancer development?
    Andrea I McClatchey
    Massachusetts General Hospital Cancer Center, Harvard Medical School Department of Pathology, 149 13th Street, Charlestown, Massachusetts 02129, USA
    Nat Rev Cancer 3:877-83. 2003
  7. pmc Erbin and the NF2 tumor suppressor Merlin cooperatively regulate cell-type-specific activation of PAK2 by TGF-beta
    Mark C Wilkes
    Thoracic Diseases Research Unit, Department of Biochemistry and Molecular Biology and Mayo Clinic Cancer Center, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Dev Cell 16:433-44. 2009
    ..These results not only identify Erbin as a key determinant of epithelial resistance to TGF-beta signaling, they also show that Erbin controls Merlin tumor suppressor function by switching the functional valence of PAK2 binding...
  8. pmc The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44
    H Morrison
    Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, and University of Karlsruhe, Institute of Genetics, 76021 Karlsruhe, Germany
    Genes Dev 15:968-80. 2001
    ..At low cell density, merlin is phosphorylated, growth permissive, and exists in a complex with ezrin, moesin, and CD44. These data indicate that merlin and CD44 form a molecular switch that specifies cell growth arrest or proliferation...
  9. pmc The NF2 tumor suppressor gene product, merlin, inhibits cell proliferation and cell cycle progression by repressing cyclin D1 expression
    Guang Hui Xiao
    Human Genetics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    Mol Cell Biol 25:2384-94. 2005
    ....
  10. pmc Unfurling of the band 4.1, ezrin, radixin, moesin (FERM) domain of the merlin tumor suppressor
    S D Yogesha
    Cell Adhesion Laboratory, Department of Cancer Biology, The Scripps Research Institute, Jupiter, Florida 33458, USA
    Protein Sci 20:2113-20. 2011
    ..We conclude the "closed" tumor suppressor conformer of merlin-1 is in fact an "open" dimer whose functions are disabled by Nf2 mutations that disrupt this architecture...
  11. pmc Merlin, a "magic" linker between extracellular cues and intracellular signaling pathways that regulate cell motility, proliferation, and survival
    Ivan Stamenkovic
    Department of Oncological Sciences, Mount Sinai School of Medicine, New York, NY10029, USA
    Curr Protein Pept Sci 11:471-84. 2010
    ....
  12. doi Lack of neurofibromatosis type 2 gene promoter methylation in sporadic vestibular schwannomas
    D Koutsimpelas
    Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, Mainz, Germany
    ORL J Otorhinolaryngol Relat Spec 74:33-7. 2012
    ..For a subset of VS without detectable gene alterations, promoter inactivation by hypermethylation has been suggested. However, published data are very limited and contradictory...
  13. ncbi Chromosome 22q alterations and expression of the NF2 gene product, merlin, in gastrointestinal stromal tumors
    Lea Pylkkanen
    Department of Industrial Hygiene, Finnish Institute of Occuapational Health, Helsinki, Finland
    Hum Pathol 34:872-9. 2003
    ..The findings suggest that allelic losses at 22q are associated with high mitotic activity and recurring disease, and that alterations in the NF2 gene are unlikely to participate in the pathogenesis of GIST...
  14. ncbi Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2
    G A Rouleau
    Centre de recherche en Neuroscience, McGill University, Montreal, Quebec, Canada
    Nature 363:515-21. 1993
    ..Its deduced product has homology with proteins at the plasma membrane and cytoskeleton interface, a previously unknown site of action of tumour suppressor genes in humans...
  15. pmc Neurofibromatosis 2 (NF2) tumor suppressor merlin inhibits phosphatidylinositol 3-kinase through binding to PIKE-L
    Rong Rong
    Department of Pathology and Laboratory Medicine, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA
    Proc Natl Acad Sci U S A 101:18200-5. 2004
    ..Knocking down PIKE-L with RNA interference abolishes merlin's tumor-suppressive activity. Our data support the hypothesis that PIKE-L is an important mediator of merlin growth suppression...
  16. ncbi Impaired intercellular adhesion and immature adherens junctions in merlin-deficient human primary schwannoma cells
    C Flaiz
    Department of Clinical Neurobiology, Institute of Biomedical and Clinical Science, Peninsula College for Medicine and Dentistry, Plymouth, UK
    Glia 56:506-15. 2008
    ....
  17. ncbi Mutations in transcript isoforms of the neurofibromatosis 2 gene in multiple human tumour types
    A B Bianchi
    Department of Molecular Genetics and Cell Biology, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543 4000
    Nat Genet 6:185-92. 1994
    ..The NF2 gene may thus constitute a tumour suppressor gene of more general importance in tumorigenesis...
  18. ncbi The fat cadherin acts through the hippo tumor-suppressor pathway to regulate tissue size
    Maria Willecke
    Department of Biochemistry and Molecular Biology, University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Curr Biol 16:2090-100. 2006
    ..However, components acting upstream of Expanded and Merlin, such as transmembrane receptors, have not yet been identified...
  19. pmc Merlin is a potent inhibitor of glioma growth
    Ying Ka Ingar Lau
    Department of Oncological Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA
    Cancer Res 68:5733-42. 2008
    ..Collectively, our results show that merlin is a potent inhibitor of high-grade human glioma...
  20. ncbi Inhibition of the hyaluronan-CD44 interaction by merlin contributes to the tumor-suppressor activity of merlin
    Y Bai
    Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Oncogene 26:836-50. 2007
    ....
  21. doi Functional inactivation of NF2/merlin in human mesothelioma
    Claudio Thurneysen
    Laboratory of Molecular Oncology, Clinic and Policlinic of Oncology, University Hospital of Zurich, Häldeliweg 4, 8044 Zurich, Switzerland
    Lung Cancer 64:140-7. 2009
    ..In tumors where no NF2 truncation can be detected, NF2 is rendered inactive by phosphorylation of Ser 518 and this can be explained at least in part by an increased expression of CPI-17...
  22. ncbi Delineation of a Fat tumor suppressor pathway
    Eunjoo Cho
    Howard Hughes Medical Institute and Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA
    Nat Genet 38:1142-50. 2006
    ..melanogaster tumor suppressors, establish a basic framework for Fat signaling from receptor to transcription factor and implicate Warts as an integrator of multiple growth control signals...
  23. ncbi Upregulation of the Rac1/JNK signaling pathway in primary human schwannoma cells
    Katherine Kaempchen
    Department of Neurology, Zentrum für Klinische Forschung, University of Ulm, Helmholtzstr 8 1, 89081 Ulm, Germany
    Hum Mol Genet 12:1211-21. 2003
    ..We conclude that merlin regulates Rac activation, and suggest that this is important for human schwannoma cell dedifferentiation...
  24. ncbi Cyclic AMP-dependent protein kinase phosphorylates merlin at serine 518 independently of p21-activated kinase and promotes merlin-ezrin heterodimerization
    Kaija Alfthan
    Biomedicum Helsinki, Department of Anatomy and Pathology, Neuroscience Program, University of Helsinki and Helsinki University Hospital, FIN 00014 Helsinki, Finland
    J Biol Chem 279:18559-66. 2004
    ..This study provides further evidence on the connection between merlin and cAMP/PKA signaling and suggests a role for merlin in the cAMP/PKA transduction pathway...
  25. ncbi Akt phosphorylation regulates the tumour-suppressor merlin through ubiquitination and degradation
    Xiaoling Tang
    Department of Pathology and Laboratory Medicine, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA
    Nat Cell Biol 9:1199-207. 2007
    ..Furthermore, Akt-mediated phosphorylation leads to merlin degradation by ubiquitination. These studies demonstrate that Akt-mediated merlin phosphorylation regulates the function of merlin in the absence of an inactivating mutation...
  26. pmc NF2/merlin is a novel negative regulator of mTOR complex 1, and activation of mTORC1 is associated with meningioma and schwannoma growth
    Marianne F James
    Center for Human Genetic Research, Massachusetts General Hospital, Richard B Simches Research Building, 185 Cambridge St, Boston, MA 02114, USA
    Mol Cell Biol 29:4250-61. 2009
    ....
  27. ncbi Tumorigenesis in neurofibromatosis: new insights and potential therapies
    N Reed
    Department of Neurology, Pediatrics and Genetics, Washington University School of Medicine, Box 8111, 660 S. Euclid Avenue, St Louis, MO 63110, USA
    Trends Mol Med 7:157-62. 2001
    ..By understanding the function of these tumor suppressors, we have a unique opportunity to develop targeted pharmacotherapeutic interventions for these disorders...
  28. ncbi Neurofibromatosis 2 tumor suppressor protein, merlin, forms two functionally important intramolecular associations
    D H Gutmann
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA
    J Neurosci Res 58:706-16. 1999
    ..Lastly, we identify NF2 patient mutations that dramatically reduce each of these interactions in vitro. Based on these findings, we propose a model for merlin folding critical to its ability to function as a tumor suppressor protein...
  29. ncbi Overexpression of Merlin in B16F10 mouse melanoma cells reduces their metastatic activity: role of the cell surface heparan sulfate glycosaminoglycans
    Zoya Galcheva-Gargova
    Momenta Pharmaceuticals, Inc, Cambridge, MA 02142, USA
    Int J Oncol 32:1237-43. 2008
    ..The results obtained provide a causal link between the reorganization/changes to the cell surface HSGAGs by the overexpression of Merlin and the inhibition of the metastatic activity of the mouse melanoma B16F10 cells in vivo...
  30. doi Merlin/NF2 functions upstream of the nuclear E3 ubiquitin ligase CRL4DCAF1 to suppress oncogenic gene expression
    Jonathan Cooper
    Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Sci Signal 4:pt6. 2011
    ..We propose that Merlin mediates contact inhibition and suppresses tumorigenesis by translocating to the nucleus to inhibit CRL4(DCAF1)...
  31. ncbi Alternative transcripts in the mouse neurofibromatosis type 2 (NF2) gene are conserved and code for schwannomins with distinct C-terminal domains
    D P Huynh
    Neurogenetics Laboratory, Cedars Sinai Medical Center, UCLA School of Medicine 90048
    Hum Mol Genet 3:1075-9. 1994
    ..These results suggest that schwannomin isoforms have distinct functional roles and predict the existence of human mutations involving the C-terminus of schwannomin...
  32. ncbi Neurofibromatosis 2 tumour suppressor schwannomin interacts with betaII-spectrin
    D R Scoles
    Division of Neurology, CSMC Burns and Allen Research Institute, Cedars Sinai Medical Center, University of California School of Medicine at Los Angeles, 90048, USA
    Nat Genet 18:354-9. 1998
    ..Thus, schwannomin is a tumour suppressor directly involved in actin-cytoskeleton organization, which suggests that alterations in the cytoskeleton are an early event in the pathogenesis of some tumour types...
  33. ncbi The role of insulin-like growth factors signaling in merlin-deficient human schwannomas
    Sylwia Ammoun
    Clinical Neurobiology, Peninsula Medical School, Plymouth University, Plymouth PL68BU, United Kingdom
    Glia 60:1721-33. 2012
    ..PI3K is relevant for both IGF-IR and previously described PDGFR-β signaling in schwannoma...
  34. ncbi Immunohistochemistry study of human vestibular nerve schwannoma differentiation
    Gene Hung
    Department of Cell and Molecular Biology, House Ear Institute, Los Angeles, California
    Glia 38:363-70. 2002
    ..These results suggest that the NF2 gene might be involved in the differentiation of Schwann cells...
  35. ncbi The merlin tumor suppressor localizes preferentially in membrane ruffles
    C Gonzalez-Agosti
    Molecular Neurogenetics Unit, Massachusetts General Hospital East, Charlestown 02129, USA
    Oncogene 13:1239-47. 1996
    ..Thus, merlin is associated with motile regions of the cell and its participation in these structures may be intimately involved in control of proliferation in Schwann cells and meningeal cells...
  36. ncbi Structure-function relationships in the ezrin family and the effect of tumor-associated point mutations in neurofibromatosis 2 protein
    O Turunen
    Department of Virology, Haartman Institute, University of Helsinki, POB 21, FIN 00014 Helsinki, Finland
    Biochim Biophys Acta 1387:1-16. 1998
    ..Some known mutations are observed at a site potentially interacting with cell adhesion molecules. We will also discuss the implications of the evolutionary information and the actin-binding models in the ezrin family...
  37. pmc Universal absence of merlin, but not other ERM family members, in schwannomas
    A O Stemmer-Rachamimov
    Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, USA
    Am J Pathol 151:1649-54. 1997
    ..These data indicate that the specific loss of merlin is universal to schwannomas and is not linked to loss of ezrin, radixin, or moesin expression...
  38. pmc Binary regulation of Hippo pathway by Merlin/NF2, Kibra, Lgl, and Melted specifies and maintains postmitotic neuronal fate
    David Jukam
    Center for Developmental Genetics, Department of Biology, New York University, 100 Washington Square East, New York, NY 10003 6688, USA
    Dev Cell 21:874-87. 2011
    ..These results reveal roles for Merlin, Kibra, and Lgl in neuronal specification and maintenance and show that the Hippo pathway is reimplemented for sensory neuron fate by combining canonical and noncanonical regulatory steps...
  39. ncbi A clue to the therapy of neurofibromatosis type 2: NF2/merlin is a PAK1 inhibitor
    Yumiko Hirokawa
    Ludwig Institute for Cancer Research, Melbourne, Australia
    Cancer J 10:20-6. 2004
    ..NF2 can inhibit Ras-induced malignant transformation. However, the primary (signaling) target of NF2 in the oncogenic pathway has not been previously identified...
  40. doi Altered adhesive structures and their relation to RhoGTPase activation in merlin-deficient Schwannoma
    Christine Flaiz
    Department of Clinical Neurobiology, Institute of Biomedical and Clinical Science, Peninsula College for Medicine and Dentistry, Plymouth, UK
    Brain Pathol 19:27-38. 2009
    ....
  41. ncbi Homotypic and heterotypic interaction of the neurofibromatosis 2 tumor suppressor protein merlin and the ERM protein ezrin
    M Grönholm
    Departments of Pathology and Virology, University of Helsinki, Haartman Institute, PO Box 21 Haartmaninkatu 3, FIN 00014 Helsinki
    J Cell Sci 112:895-904. 1999
    ..These results biochemically connect merlin to the cortical cytoskeleton and indicate differential regulation of merlin from ERM proteins...
  42. ncbi Allelic loss of 14q and 22q, NF2 mutation, and genetic instability occur independently of c-kit mutation in gastrointestinal stromal tumor
    T Fukasawa
    Department of Pathology, Jichi Medical School, Minami Kawachi Machi, Kawachi, Tochigi 329 0498, Japan
    Jpn J Cancer Res 91:1241-9. 2000
    ..NF2 contributes as a tumor suppressor in a small subset of GIST. These abnormalities are presumably followed by increased genetic instability...
  43. pmc Nilotinib alone or in combination with selumetinib is a drug candidate for neurofibromatosis type 2
    Sylwia Ammoun
    Clinical Neurobiology, Peninsula College for Medicine and Dentistry, The John Bull Building, Tamar Science Park, Research Way, Plymouth PL6 8BU, United Kingdom
    Neuro Oncol 13:759-66. 2011
    ..We suggest that therapy with nilotinib or combinational therapy that  simultaneously inhibits PDGFR and the downstream Raf/MEK1/2/ERK1/2 pathway could represent an effective treatment for schwannomas and other merlin-deficient tumors...
  44. ncbi A genetic screen in zebrafish identifies the mutants vps18, nf2 and foie gras as models of liver disease
    Kirsten C Sadler
    Center for Cancer Research, Massachusetts Institute of Technology, Cambridge MA 02139, USA
    Development 132:3561-72. 2005
    ..These mutants illustrate the utility of zebrafish as a model for studying liver development and disease, and provide valuable tools for investigating the molecular pathogenesis of congenital biliary disorders and fatty liver disease...
  45. ncbi The tumor suppressors Merlin and Expanded function cooperatively to modulate receptor endocytosis and signaling
    Sushmita Maitra
    Department of Molecular Genetics and Cell Biology, University of Chicago, Illinois 60637, USA
    Curr Biol 16:702-9. 2006
    ..We propose that these proteins control proliferation by regulating the abundance, localization, and turnover of cell-surface receptors and that misregulation of these processes may be a key component of tumorigenesis...
  46. ncbi Erbin regulates mitogen-activated protein (MAP) kinase activation and MAP kinase-dependent interactions between Merlin and adherens junction protein complexes in Schwann cells
    Reshma Rangwala
    Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon 97006, USA
    J Biol Chem 280:11790-7. 2005
    ..Collectively, these data indicate that erbin regulates MAP kinase activation in Schwann cells and suggest that erbin links merlin to both adherens junction protein complexes and the MAP kinase signaling pathway...
  47. ncbi Merlin/neurofibromatosis type 2 suppresses growth by inhibiting the activation of Ras and Rac
    Helen Morrison
    Institute of Age Research, Fritz Lipmann Institute, Jena, Germany
    Cancer Res 67:520-7. 2007
    ..We propose that the interference of merlin with Ras- and Rac-dependent signal transfer represents part of the tumor-suppressive action of merlin...
  48. pmc Mice heterozygous for a mutation at the Nf2 tumor suppressor locus develop a range of highly metastatic tumors
    A I McClatchey
    Department of Biology and the Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Genes Dev 12:1121-33. 1998
    ..Together, our results suggest an important role for the NF2 tumor suppressor, and perhaps the ERM family in tumor formation and metastasis...
  49. ncbi Interdomain interaction of merlin isoforms and its influence on intermolecular binding to NHE-RF
    C Gonzalez-Agosti
    Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Biol Chem 274:34438-42. 1999
    ....
  50. ncbi NF2 expression levels of gastrointestinal stromal tumors: a quantitative real-time PCR study
    Antonio Taddei
    Department of Surgical Pathology, University of Florence, School of Medicine, Florence, Italy
    Tumori 94:551-5. 2008
    ..NF2 gene mRNA expression was assessed in fresh tissue of stomach from 5 consecutive patients. We detected no alterations in NF2 gene expression in the quantitative analyses of the 5 tumors...
  51. ncbi Magic but treatable? Tumours due to loss of merlin
    C O Hanemann
    Clinical Neurobiology, Peninsula Medical School, The John Bull Building, Tamar Science Park, Research Way, Plymouth, PL6 8BU, UK
    Brain 131:606-15. 2008
    ..Finally, I will discuss how loss of merlin leads to tumourigenesis in order to understand the rationale for emerging new therapeutic targets...
  52. ncbi p21-activated kinase links Rac/Cdc42 signaling to merlin
    Guang Hui Xiao
    Human Genetics Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Biol Chem 277:883-6. 2002
    ..These biochemical investigations provide insights into the regulation of merlin function and establish a framework for elucidating tumorigenic mechanisms involved in neoplasms associated with merlin inactivation...
  53. ncbi Increased expression of the NF2 tumor suppressor gene product, merlin, impairs cell motility, adhesionand spreading
    D H Gutmann
    The Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    Hum Mol Genet 8:267-75. 1999
    ..These data indicate that merlin may function to maintain normal cytoskeletal organization, and suggest that merlin's influence on cell growth depends on specific cytoskeletal rearrangements...
  54. pmc Localization to the cortical cytoskeleton is necessary for Nf2/merlin-dependent epidermal growth factor receptor silencing
    Banumathi K Cole
    Massachusetts General Hospital East, 149 CNY 13th St, Charlestown, MA 02129, USA
    Mol Cell Biol 28:1274-84. 2008
    ....
  55. ncbi The 2.7 A crystal structure of the activated FERM domain of moesin: an analysis of structural changes on activation
    S D Edwards
    BBSRC Bloomsbury Centre for Structural Biology and School of Crystallography, Birkbeck College, University of London, Malet Street, London WC1E 7HX, UK
    Biochemistry 40:7061-8. 2001
    ..More interestingly, a negatively charged peptide binds to the inositol site in a crystal contact and causes a greater conformational change in the structure than inositol...
  56. ncbi The NF2 interactor, hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), associates with merlin in the "open" conformation and suppresses cell growth and motility
    D H Gutmann
    Department of Neurology, Washington University School of Medicine, Box 8111, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Hum Mol Genet 10:825-34. 2001
    ..These results suggest the possibility that merlin and HRS may regulate cell growth in schwannoma cells through interacting pathways...
  57. ncbi Normal membrane localization and actin association of the NF2 tumor suppressor protein are dependent on folding of its N-terminal domain
    E Brault
    , U434 INSERM-CEPH Fondation Jean Dausset, 75010 Paris, France
    J Cell Sci 114:1901-12. 2001
    ..These results suggest that loss of activity of several naturally occurring schwannomin mutants is due to disruption of the fold of the N-terminal domain, leading to loss of both membrane localization and actin association...
  58. ncbi A NHERF binding site links the betaPDGFR to the cytoskeleton and regulates cell spreading and migration
    Marianne F James
    Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Building 149, 13th Street, Charlestown, MA 02129, USA
    J Cell Sci 117:2951-61. 2004
    ..Thus, the interaction of betaPDGFR with NHERF may provide an essential link between the cell membrane and the cortical actin cytoskeleton independent of receptor activity...
  59. pmc NF2 deficiency promotes tumorigenesis and metastasis by destabilizing adherens junctions
    Dominique Lallemand
    MGH Cancer Center and Harvard Medical School Department of Pathology, Charlestown, Massachusetts 02129, USA
    Genes Dev 17:1090-100. 2003
    ..Our studies indicate that merlin functions as a tumor and metastasis suppressor by controlling cadherin-mediated cell:cell contact...
  60. pmc Phosphorylation and activity of the tumor suppressor Merlin and the ERM protein Moesin are coordinately regulated by the Slik kinase
    Sarah C Hughes
    Department of Cell Biology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada
    J Cell Biol 175:305-13. 2006
    ..These results suggest the existence of a novel mechanism for coordinate regulation of cell proliferation and epithelial integrity in developing tissues...
  61. pmc Mixed-lineage kinase 3 regulates B-Raf through maintenance of the B-Raf/Raf-1 complex and inhibition by the NF2 tumor suppressor protein
    Deborah N Chadee
    Molecular Cardiology Research Institute, Tufts New England Medical Center, Tufts University School of Medicine, 750 Washington Street, Boston, MA 02111, USA
    Proc Natl Acad Sci U S A 103:4463-8. 2006
    ..Thus, MLK3 is part of a multiprotein complex and is required for ERK activation. The levels of this complex may be negatively regulated by merlin...
  62. ncbi Inhibition of ras-mediated activator protein 1 activity and cell growth by merlin
    Hongtae Kim
    Neuroscience Genome Research Center, The Catholic University of Korea, Seoul
    Mol Cells 14:108-14. 2002
    ....
  63. ncbi NHE-RF, a regulatory cofactor for Na(+)-H+ exchange, is a common interactor for merlin and ERM (MERM) proteins
    A Murthy
    Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown 02129, USA
    J Biol Chem 273:1273-6. 1998
    ....
  64. ncbi Cellular transformation by a FERM domain mutant of the Nf2 tumor suppressor gene
    Kristen C Johnson
    Department of Biology and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, MA 02139, USA
    Oncogene 21:5990-7. 2002
    ..Finally, fibroblasts that express this mutant Nf2 allele form tumors when injected into nude mice...
  65. ncbi ERM proteins and merlin: integrators at the cell cortex
    Anthony Bretscher
    Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA
    Nat Rev Mol Cell Biol 3:586-99. 2002
    ..The closely related tumour suppressor merlin shares many properties with ERM proteins, yet also provides a distinct and essential function...
  66. pmc Distinct cellular and subcellular patterns of expression imply distinct functions for the Drosophila homologues of moesin and the neurofibromatosis 2 tumor suppressor, merlin
    B M McCartney
    Department of Zoology, Duke University, Durham, North Carolina 27708 1000, USA
    J Cell Biol 133:843-52. 1996
    ..As a result of these studies, we propose that the merlin protein has unique functions in the cell which differ from those of other ERM family members...
  67. ncbi Paxillin binds schwannomin and regulates its density-dependent localization and effect on cell morphology
    Cristina Fernandez-Valle
    Department of Molecular Biology and Microbiology, University of Central Florida, Orlando, Florida 32826, USA
    Nat Genet 31:354-62. 2002
    ..It defines a pathogenic mechanism for the development of NF2 in humans with mutations in exon 2 of NF2...
  68. ncbi Merlin, the product of the Nf2 tumor suppressor gene, is an inhibitor of the p21-activated kinase, Pak1
    Joseph L Kissil
    Department of Biology and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Mol Cell 12:841-9. 2003
    ..This link provides a possible mechanism for the effect of loss of merlin expression in tumorigenesis...
  69. pmc Merlin/NF-2 mediates contact inhibition of growth by suppressing recruitment of Rac to the plasma membrane
    Tomoyo Okada
    Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Cell Biol 171:361-71. 2005
    ..These results provide a framework for understanding the tumor suppressor function of Merlin and indicate that Merlin mediates contact inhibition of growth by suppressing recruitment of Rac to matrix adhesions...
  70. ncbi Merlin and the ERM proteins in Schwann cells, neurons and growth cones
    Vijaya Ramesh
    Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    Nat Rev Neurosci 5:462-70. 2004
  71. pmc Structural analysis of Drosophila merlin reveals functional domains important for growth control and subcellular localization
    D R LaJeunesse
    Developmental, Cell and Molecular Biology Group, Department of Zoology, Duke University, Durham, North Carolina 27708 1000, USA
    J Cell Biol 141:1589-99. 1998
    ..These results provide insights into the functions and functional organization of a novel tumor suppressor gene...
  72. ncbi Effect of merlin phosphorylation on neurofibromatosis 2 (NF2) gene function
    Ezequiel I Surace
    Department of Neurology, Washington University School of Medicine, Box 8111, 660 S Euclid Avenue, St Louis, MO 63110, USA
    Oncogene 23:580-7. 2004
    ....
  73. ncbi The NF2 tumor suppressor Merlin and the ERM proteins interact with N-WASP and regulate its actin polymerization function
    Nitasha Manchanda
    Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Biol Chem 280:12517-22. 2005
    ..This novel function of merlin and the ERMs illustrates a mechanism by which these proteins directly exert their effects on actin reorganization and also provides new insight into N-WASP regulation...
  74. ncbi Activation of the tumor suppressor merlin modulates its interaction with lipid rafts
    John T Stickney
    Department of Cell Biology, Neurobiology, and Anatomy, Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    Cancer Res 64:2717-24. 2004
    ....
  75. pmc Evolution and origin of merlin, the product of the Neurofibromatosis type 2 (NF2) tumor-suppressor gene
    Kseniya Golovnina
    Institute of Cytology and Genetics, Russian Academy of Sciences, 630090, Novosibirsk, Russia
    BMC Evol Biol 5:69. 2005
    ..While merlin's functional activity has been examined in mammalian and Drosophila models, little is understood about its evolution, diversity, and overall distribution among different taxa...
  76. ncbi Serine 518 phosphorylation modulates merlin intramolecular association and binding to critical effectors important for NF2 growth suppression
    Rong Rong
    Department of Pathology and Laboratory Medicine, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA
    Oncogene 23:8447-54. 2004
    ..These observations suggest that merlin S518 phosphorylation directly modulates merlin intramolecular and intermolecular associations important for the ability of merlin to function as a tumor suppressor...
  77. pmc The Drosophila tumor suppressors Expanded and Merlin differentially regulate cell cycle exit, apoptosis, and Wingless signaling
    Brett J Pellock
    Massachusetts General Hospital Cutaneous Biology Research Center, Charlestown, MA 02129, and University of California, Berkeley, Department of Molecular and Cell Biology 94720, USA
    Dev Biol 304:102-15. 2007
    ..Finally, ex has a role in regulating Wingless protein levels in the eye that is not obviously shared by either mer or hpo. Taken together, our data suggest that Mer and Ex differentially regulate multiple downstream pathways...
  78. ncbi Membrane organization and tumorigenesis--the NF2 tumor suppressor, Merlin
    Andrea I McClatchey
    Massachusetts General Hospital, Center for Cancer Research and Harvard Medical School, Department of Pathology, Charlestown, Massachusetts 02129, USA
    Genes Dev 19:2265-77. 2005
    ..Varying use of this organizing activity by different types of cells could provide an explanation for the unique spectrum of tumors associated with NF2 deficiency in mammals...
  79. ncbi Merlin differentially associates with the microtubule and actin cytoskeleton
    H M Xu
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci Res 51:403-15. 1998
    ..These microtubule association results confirm the notion that merlin exists in "open" and "closed" conformations relevant to its function as a negative growth regulator...
  80. ncbi Merlin phosphorylation by p21-activated kinase 2 and effects of phosphorylation on merlin localization
    Joseph L Kissil
    Department of Biology and Center for Cancer Research and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Biol Chem 277:10394-9. 2002
    ..By using wild-type and mutated forms of merlin and phospho-directed antibodies, we show that phosphorylation of merlin at serine 518 leads to dramatic protein relocalization...
  81. ncbi The Nf2 tumor suppressor, merlin, functions in Rac-dependent signaling
    R J Shaw
    Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139, USA
    Dev Cell 1:63-72. 2001
    ..Finally, Nf2-/- cells exhibit characteristics of cells expressing activated alleles of Rac. These studies provide insight into the normal cellular function of merlin and how Nf2 mutation contributes to tumor initiation and progression...
  82. ncbi Structural basis for neurofibromatosis type 2. Crystal structure of the merlin FERM domain
    Toshiyuki Shimizu
    Structural Biology Laboratory, Nara Institute of Science and Technology and CREST, Japan
    J Biol Chem 277:10332-6. 2002
    ..The structure also is consistent with inactivation mechanisms caused by the pathogenic mutations associated with NF2...
  83. pmc Loss of the tumor suppressor gene NF2, encoding merlin, constitutively activates integrin-dependent mTORC1 signaling
    Miguel A López-Lago
    Cell Biology Program, Sloan Kettering Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA
    Mol Cell Biol 29:4235-49. 2009
    ....
  84. pmc A systematic screen for dominant second-site modifiers of Merlin/NF2 phenotypes reveals an interaction with blistered/DSRF and scribbler
    D R LaJeunesse
    Developmental, Cell and Molecular Biology Group, Department of Biology, Duke University, Durham, North Carolina 27708 1000, USA
    Genetics 158:667-79. 2001
    ..These results suggest that Merlin, blistered, and scribbler function together in a common pathway to regulate Drosophila wing epithelial development...
  85. ncbi Functional analysis of neurofibromatosis 2 (NF2) missense mutations
    D H Gutmann
    Department of Neurology, Washington University School of Medicine, Box 8111, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Hum Mol Genet 10:1519-29. 2001
    ..These results suggest that the key functional domains of merlin lie within the highly conserved FERM domain and the unique C-terminus of the protein...
  86. pmc The neurofibromatosis 2 protein product merlin selectively binds F-actin but not G-actin, and stabilizes the filaments through a lateral association
    M F James
    Molecular Neurogenetics Unit, Massachusetts General Hospital, Building 149, 13th Street, Charlestown, MA 02129, USA
    Biochem J 356:377-86. 2001
    ..Comparison of these findings with those reported for ERM proteins reveal a distinct role for merlin in actin filament dynamics...
  87. ncbi Hierarchy of merlin and ezrin N- and C-terminal domain interactions in homo- and heterotypic associations and their relationship to binding of scaffolding proteins EBP50 and E3KARP
    R Nguyen
    Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA
    J Biol Chem 276:7621-9. 2001
    ..E3KARP binds tightly to the ezrin N-ERMAD but has little affinity for the merlin N-ERMAD. The implications of these associations and the hierarchies of binding for the function and regulation of merlin and ERM proteins are discussed...
  88. ncbi Shedding light on Merlin's wizardry
    Tomoyo Okada
    Cell Biology Program, Sloan Kettering Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Trends Cell Biol 17:222-9. 2007
    ..Here, we review these recent findings and their relevance to the tumor suppressor function of Merlin...
  89. ncbi Merlin, the Drosophila homologue of neurofibromatosis-2, is specifically required in posterior follicle cells for axis formation in the oocyte
    N MacDougall
    Wellcome Centre for Cell Biology, ICMB, King s Buildings, University of Edinburgh, Edinburgh EH9 3JR, UK
    Development 128:665-73. 2001
    ..We propose that Merlin acts in response to the Gurken signal by apically targeting the signal that initiates axis specification in the oocyte...
  90. ncbi ERM proteins and NF2 tumor suppressor: the Yin and Yang of cortical actin organization and cell growth signaling
    Alexis Gautreau
    UMR 144 CNRS Institut Curie, 26 Rue d Ulm, 75248 Cedex 05, Paris, France
    Curr Opin Cell Biol 14:104-9. 2002
    ..Recent studies have revealed that ERM proteins transduce growth signals, and have shed new light on how merlin links cell growth to the cytoskeleton...
  91. ncbi Tumorigenic transformation by CPI-17 through inhibition of a merlin phosphatase
    Hongchuan Jin
    Leibniz Institute of Age Research Fritz Lipmann Institute, Beutenbergstrasse 11, 07745 Jena, Germany
    Nature 442:576-9. 2006
    ..MYPT-1-PP1delta and its substrate merlin are part of a previously undescribed tumour suppressor cascade that can be hindered in two ways, by mutation of the NF2 gene and by upregulation of the oncoprotein CPI-17...
  92. pmc Nf2 gene inactivation in arachnoidal cells is rate-limiting for meningioma development in the mouse
    Michel Kalamarides
    INSERM U434, Fondation Jean Dausset Centre d Etude du Polymorphisme Humain, 75010 Paris, France
    Genes Dev 16:1060-5. 2002
    ..This first mouse model initiated with a genetic lesion found in human meningiomas provides a powerful tool for investigating tumor progression and for the preclinical evaluation of therapeutic interventions...
  93. ncbi The tumor suppressor merlin interacts with microtubules and modulates Schwann cell microtubule cytoskeleton
    Taru Muranen
    Program of Neuroscience, Department of Pathology, University of Helsinki, Biomedicum Helsinki C511, PL 63, 0014, Finland
    Hum Mol Genet 16:1742-51. 2007
    ..The results show that merlin plays a key role in the regulation of the Schwann cell microtubule cytoskeleton and suggest a mechanism by which loss of merlin leads to cytoskeletal defects observed in human schwannomas...
  94. pmc The Nf2 tumor suppressor regulates cell-cell adhesion during tissue fusion
    Margaret E McLaughlin
    Department of Biology and Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 104:3261-6. 2007
    ..Our work reveals that regulation of Nf2 expression is a previously unrecognized means of controlling adhesion at the leading front, thereby ensuring successful tissue fusion...
  95. ncbi The neurofibromatosis-2 homologue, Merlin, and the tumor suppressor expanded function together in Drosophila to regulate cell proliferation and differentiation
    B M McCartney
    Developmental, Cell and Molecular Biology Group, Duke University, Durham, NC 27708 1000, USA
    Development 127:1315-24. 2000
    ..These results indicate that Merlin and Expanded function together to regulate proliferation and differentiation, and have implications for understanding the functions of other Protein 4.1 superfamily members...
  96. ncbi Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain
    M A Pearson
    Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA
    Cell 101:259-70. 2000
    ..This extended binding mode suggests a novel mechanism for how different signals could produce varying levels of activation. Sequence conservation suggests a similar regulation of the tumor suppressor merlin...
  97. pmc The neurofibromatosis type 2 gene product, merlin, reverses the F-actin cytoskeletal defects in primary human Schwannoma cells
    Anne Marie Bashour
    Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA
    Mol Cell Biol 22:1150-7. 2002
    ..These results lay the foundation for epigenetic complementation studies in NF2 mouse models and possibly for experiments to evaluate the utility of merlin transduction into patients as protein therapy...
  98. ncbi Novel alternatively spliced isoforms of the neurofibromatosis type 2 tumor suppressor are targeted to the nucleus and cytoplasmic granules
    B Schmucker
    Institute of Human Genetics, University of Erlangen, Germany
    Hum Mol Genet 8:1561-70. 1999
    ..Although the NF2 protein is known as a cytoskeletal linker, additional functions in a cytoplasmic compartment and in the nucleus may exist...
  99. pmc Binding of the merlin-I product of the neurofibromatosis type 2 tumour suppressor gene to a novel site in beta-fodrin is regulated by association between merlin domains
    G W Neill
    Centre for Cutaneous Research, St Bartholomew s and The Royal London, Queen Mary and Westfield College, 2 Newark Street, London E1 2AT, UK
    Biochem J 358:727-35. 2001
    ....
  100. ncbi Expression of the neurofibromatosis 2 (NF2) gene isoforms during rat embryonic development
    D H Gutmann
    Department of Neurology, Washington University School of Medicine, St Louis, MO, USA
    Hum Mol Genet 4:471-8. 1995
    ....
  101. ncbi The neurofibromatosis 2 (NF2) tumor suppressor gene encodes multiple alternatively spliced transcripts
    M J Pykett
    Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia 19104 6145
    Hum Mol Genet 3:559-64. 1994
    ..They also should be considered in studies investigating mutations of this gene in members of NF2 families and in tumor analyses...

Research Grants87

  1. Contribution of c-Jun N-terminal kinase activity to vestibular schwannoma growth
    Marlan R Hansen; Fiscal Year: 2010
    ..These studies seek to identify the underlying cellular abnormalities that lead to tumor formation and to identify novel therapies that specifically limit schwannoma growth. ..
  2. Contribution of c-Jun N-terminal kinase activity to vestibular schwannoma growth
    Marlan Hansen; Fiscal Year: 2009
    ..These studies seek to identify the underlying cellular abnormalities that lead to tumor formation and to identify novel therapies that specifically limit schwannoma growth. ..
  3. Role of CD98 Glycoprotein in Intestinal Inflammation
    Hamed Laroui; Fiscal Year: 2012
    ..g. DDW and FASEB), and receive guidance from a selected Career Development Research Advisory Committee. ..
  4. Growth Factor-Induced Peripheral Gliogenesis
    Donald Pizzo; Fiscal Year: 2006
    ..Furthermore, the development of a quantitative tumor model allows for the assessment of small molecule therapeutics in a pre-clinical setting. [unreadable] [unreadable]..
  5. Growth Factor-Induced Peripheral Gliogenesis
    Donald Pizzo; Fiscal Year: 2007
    ..Furthermore, the development of a quantitative tumor model allows for the assessment of small molecule therapeutics in a pre-clinical setting. [unreadable] [unreadable]..
  6. Growth Factor-Induced Peripheral Gliogenesis
    Donald Pizzo; Fiscal Year: 2004
    ..Furthermore, the development of a quantitative tumor model allows for the assessment of small molecule therapeutics in a pre-clinical setting. ..
  7. Growth Factor-Induced Peripheral Gliogenesis
    Donald Pizzo; Fiscal Year: 2005
    ..Furthermore, the development of a quantitative tumor model allows for the assessment of small molecule therapeutics in a pre-clinical setting. ..
  8. Mechanism of Merlin-mediated contact inhibition and tumor suppression.
    Filippo G Giancotti; Fiscal Year: 2010
    ..It is expected that a mechanistic understanding of Merlin's function will shed light on contact inhibition and on the pathogenesis of NF2 mutant tumors. ..
  9. Molecular Genetics of Inherited Neurological Diseases
    Xandra Breakefield; Fiscal Year: 2002
    ..Collectively these studies provide a concerted effort towards understanding the neurologic functions of NF2 and TSC genes and treating disease manifestations associated with these diseases. ..
  10. Molecular Genetics of Inherited Neurological Diseases
    Xandra Breakefield; Fiscal Year: 2005
    ..Collectively these studies provide a concerted effort towards understanding the neurologic functions of NF2 and TSC genes and treating disease manifestations associated with these diseases. ..
  11. Molecular Genetics of Inherited Neurological Diseases
    Xandra Breakefield; Fiscal Year: 2001
    ..Collectively these studies provide a concerted effort towards understanding the neurologic functions of NF2 and TSC genes and treating disease manifestations associated with these diseases. ..
  12. Molecular Genetics of Inherited Neurological Diseases
    Xandra Breakefield; Fiscal Year: 2003
    ..Collectively these studies provide a concerted effort towards understanding the neurologic functions of NF2 and TSC genes and treating disease manifestations associated with these diseases. ..
  13. Molecular Genetics of Inherited Neurological Diseases
    Xandra Breakefield; Fiscal Year: 2004
    ..Collectively these studies provide a concerted effort towards understanding the neurologic functions of NF2 and TSC genes and treating disease manifestations associated with these diseases. ..
  14. MLK3 function in neurofibromatosis tumor cells
    John Kyriakis; Fiscal Year: 2009
    ..Alternatively, merlin could repress the recruitment of MLK3 by Rho family GTPases. In Aim 3, we will use biochemical and molecular biological methods to explore these possibilities. ..
  15. MLK3 function in neurofibromatosis tumor cells
    John Kyriakis; Fiscal Year: 2007
    ..Alternatively, merlin could repress the recruitment of MLK3 by Rho family GTPases. In Aim 3, we will use biochemical and molecular biological methods to explore these possibilities. ..
  16. MLK3 function in neurofibromatosis tumor cells
    John Kyriakis; Fiscal Year: 2006
    ..Alternatively, merlin could repress the recruitment of MLK3 by Rho family GTPases. In Aim 3, we will use biochemical and molecular biological methods to explore these possibilities. ..
  17. MLK3 function in neurofibromatosis tumor cells
    John Kyriakis; Fiscal Year: 2005
    ..Alternatively, merlin could repress the recruitment of MLK3 by Rho family GTPases. In Aim 3, we will use biochemical and molecular biological methods to explore these possibilities. ..
  18. MOLECULAR GENETIC ALTERATIONS IN MALIGNANT MESOTHELIOMA
    JOSEPH TESTA; Fiscal Year: 2004
    ..Overall, these studies are expected to provide insights regarding mechanisms by which specific TSGs contribute to the pathogenesis of MM and delineate potential avenues for therapeutic intervention. ..
  19. MOLECULAR GENETIC ALTERATIONS IN MALIGNANT MESOTHELIOMA
    JOSEPH TESTA; Fiscal Year: 2005
    ..Overall, these studies are expected to provide insights regarding mechanisms by which specific TSGs contribute to the pathogenesis of MM and delineate potential avenues for therapeutic intervention. ..
  20. MOLECULAR GENETIC ALTERATIONS IN MALIGNANT MESOTHELIOMA
    JOSEPH TESTA; Fiscal Year: 2002
    ..Overall, these studies are expected to provide insights regarding mechanisms by which specific TSGs contribute to the pathogenesis of MM and delineate potential avenues for therapeutic intervention. ..
  21. MOLECULAR GENETIC ALTERATIONS IN MALIGNANT MESOTHELIOMA
    JOSEPH TESTA; Fiscal Year: 2006
    ..Overall, these studies are expected to provide insights regarding mechanisms by which specific TSGs contribute to the pathogenesis of MM and delineate potential avenues for therapeutic intervention. ..
  22. MOLECULAR GENETIC ALTERATIONS IN MALIGNANT MESOTHELIOMA
    JOSEPH TESTA; Fiscal Year: 2003
    ..Overall, these studies are expected to provide insights regarding mechanisms by which specific TSGs contribute to the pathogenesis of MM and delineate potential avenues for therapeutic intervention. ..
  23. MOLECULAR GENETICS OF INHERITED NEUROLOGIC DISEASES
    Xandra Breakefield; Fiscal Year: 1999
    ....
  24. Molecular Genetics Of Meningioma and Neurofibromatosis Related Disorders
    James F Gusella; Fiscal Year: 2011
    ..abstract_text> ..
  25. Molecular Genetics of Inherited Neurological Diseases
    Xandra Breakefield; Fiscal Year: 2009
    ....
  26. Molecular Genetics of Inherited Neurological Diseases
    Xandra Breakefield; Fiscal Year: 2009
    ....
  27. MOLECULAR GENETICS OF MENINGIOMA AND NF-RELATED DISORDERS
    James Gusella; Fiscal Year: 2001
    ..Overall, our studies should improve our understanding of the molecular biology behind slow-growing, benign tumors affecting the nervous system and provide clues for development of novel therapies. ..
  28. FUNCTIONAL ANALYSIS OF NF2 GENE MUTATIONS
    David Gutmann; Fiscal Year: 1999
    ....
  29. Accurate detection of chromosomal abnormalities with multi-color image processing
    Yu Ping Wang; Fiscal Year: 2009
    ..This will in turn benefit the health of human beings. Furthermore, the developed computational techniques can be applicable to a wide range of multi-color bio-imaging problems, thereby having a broad impact on the biomedical community. ..
  30. Control of cell number in developing retina
    Duojia Pan; Fiscal Year: 2012
    ..Such insights may facilitate the therapeutic interventions of relevant human diseases, including diseases of the retina. ..
  31. Control of cell number in developing retina
    Duojia Pan; Fiscal Year: 2010
    ..Such insights may facilitate the therapeutic interventions of relevant human diseases, including diseases of the retina. ..
  32. Computational and Statistical Models for Human Pedigrees
    Goncalo Abecasis; Fiscal Year: 2004
    ..abstract_text> ..
  33. Computational and Statistical Models for Human Pedigrees
    Goncalo Abecasis; Fiscal Year: 2007
    ..abstract_text> ..
  34. Computational and Statistical Models for Human Pedigrees
    Goncalo Abecasis; Fiscal Year: 2006
    ..abstract_text> ..
  35. Computational and Statistical Models for Human Pedigrees
    Goncalo Abecasis; Fiscal Year: 2004
    ..abstract_text> ..
  36. Computational and Statistical Models for Human Pedigrees
    Goncalo Abecasis; Fiscal Year: 2003
    ..abstract_text> ..
  37. CONTROL OF SCHWANN CELL DIFFERENTIATION
    Cristina Fernandez Valle; Fiscal Year: 2000
    ....
  38. CONTROL OF SCHWANN CELL DIFFERENTIATION
    Cristina Fernandez Valle; Fiscal Year: 2001
    ....
  39. CONTROL OF SCHWANN CELL DIFFERENTIATION
    Cristina Fernandez Valle; Fiscal Year: 1999
    ....
  40. ErbB receptor regulation of Vestibular Schwannomas
    JONI DOHERTY; Fiscal Year: 2009
    ..Treatment is limited to surgery or radiation. The proposed project investigates the molecular events that cause vestibular schwannomas with the goal of developing a new medical treatment alternative. ..
  41. ErbB receptor regulation of Vestibular Schwannomas
    JONI DOHERTY; Fiscal Year: 2007
    ..Treatment is limited to surgery or radiation. The proposed project investigates the molecular events that cause vestibular schwannomas with the goal of developing a new medical treatment alternative. ..
  42. PROTEIN 4.1 TUMOR SUPPRESSORS IN MENINGIOMA PATHOGENESIS
    David Gutmann; Fiscal Year: 2001
    ..and (3) analyzing the ability of DAL-1 to impair cell growth and motility. These studies are collectively designed to define the role of this novel family of growth regulators in meningioma tumorigenesis and progression. ..
  43. PROTEIN 4.1 TUMOR SUPPRESSORS IN MENINGIOMA PATHOGENESIS
    David Gutmann; Fiscal Year: 2002
    ..and (3) analyzing the ability of DAL-1 to impair cell growth and motility. These studies are collectively designed to define the role of this novel family of growth regulators in meningioma tumorigenesis and progression. ..
  44. FUNCTION OF MERLIN, A DROSOPHILA NF2 GENE HOMOLOGUE
    Richard G Fehon; Fiscal Year: 2010
    ..Finally, these studies should contribute to work on the mechanisms by which cellular interactions function to control cell growth and determine cell fate during development. ..
  45. FACTORS CONTROLLING LENS EPITHELIAL DIFFERENTIATION
    David Beebe; Fiscal Year: 1999
    ..Mouse lenses from animals with one defective NF2 gene will be used to determine whether accumulated DNA damage is the cause of several kinds of cataracts. ..
  46. FACTORS CONTROLLING LENS EPITHELIAL DIFFERENTIATION
    David Beebe; Fiscal Year: 2000
    ..Mouse lenses from animals with one defective NF2 gene will be used to determine whether accumulated DNA damage is the cause of several kinds of cataracts. ..
  47. CHARACTERIZATION OF MERLIN EXPRESSION
    James Gusella; Fiscal Year: 1999
    ..In the long- term, this line of investigation may form the foundation on which to develop effective treatments to prevent the formation or to slow the growth of the tumors associated with NF2 and their sporadic counterparts. ..
  48. Schwann Cells in Neurofibromatosis Type 2 (NF2)
    Nancy Ratner; Fiscal Year: 2010
    ..The proposed studies are expected to provide insight into regulation of normal axon-glial interactions, and to lead to strategies to understand and ultimately treat human schwannomas. ..
  49. Schwann Cells in Neurofibromatosis Type 2 (NF2)
    Nancy Ratner; Fiscal Year: 2009
    ..The proposed studies are expected to provide insight into regulation of normal axon-glial interactions, and to lead to strategies to understand and ultimately treat human schwannomas. ..
  50. Schwann Cells in Neurofibromatosis Type 2 (NF2)
    Nancy Ratner; Fiscal Year: 2007
    ..The proposed studies are expected to provide insight into regulation of normal axon-glial interactions, and to lead to strategies to understand and ultimately treat human schwannomas. ..
  51. AKT AND TUMOR SUPPRESSOR PATHWAYS IN MESOTHELIOMA
    JOSEPH TESTA; Fiscal Year: 2006
    ..abstract_text> ..
  52. FUNCTIONAL ANALYSIS OF NF2 GENE MUTATIONS
    David Gutmann; Fiscal Year: 2001
    ..Our ability to design rational therapies for schwannomas and meningiomas is dependent on an improved understanding of the mechanisms by which loss of merlin expression and function promotes tumor formation. ..
  53. FUNCTIONAL ANALYSIS OF NF2 GENE MUTATIONS
    David Gutmann; Fiscal Year: 2000
    ..Our ability to design rational therapies for schwannomas and meningiomas is dependent on an improved understanding of the mechanisms by which loss of merlin expression and function promotes tumor formation. ..
  54. FUNCTIONAL ANALYSIS OF NF2 GENE MUTATIONS
    David Gutmann; Fiscal Year: 2000
    ..Our ability to design rational therapies for schwannomas and meningiomas is dependent on an improved understanding of the mechanisms by which loss of merlin expression and function promotes tumor formation. ..
  55. FUNCTIONAL ANALYSIS OF NF2 GENE MUTATIONS
    David Gutmann; Fiscal Year: 2002
    ..Our ability to design rational therapies for schwannomas and meningiomas is dependent on an improved understanding of the mechanisms by which loss of merlin expression and function promotes tumor formation. ..
  56. Computational and Statistical Models for Human Pedigrees
    Goncalo Abecasis; Fiscal Year: 2005
    ..abstract_text> ..
  57. Structure, Function and Regulation of Merlin
    Wallace Ip; Fiscal Year: 2009
    ..We anticipate that these studies will shed new light on pathways involved in merlin-mediated tumor suppression, and may suggest possible molecular targets for therapeutic strategies for tumors that arise from loss of merlin function. ..
  58. Structure, Function and Regulation of Merlin
    Wallace Ip; Fiscal Year: 2006
    ..We anticipate that these studies will shed new light on pathways involved in merlin-mediated tumor suppression, and may suggest possible molecular targets for therapeutic strategies for tumors that arise from loss of merlin function. ..
  59. Structure, Function and Regulation of Merlin
    Wallace Ip; Fiscal Year: 2009
    ..We anticipate that these studies will shed new light on pathways involved in merlin-mediated tumor suppression, and may suggest possible molecular targets for therapeutic strategies for tumors that arise from loss of merlin function. ..
  60. Structure, Function and Regulation of Merlin
    Wallace Ip; Fiscal Year: 2007
    ..We anticipate that these studies will shed new light on pathways involved in merlin-mediated tumor suppression, and may suggest possible molecular targets for therapeutic strategies for tumors that arise from loss of merlin function. ..
  61. Structure, Function and Regulation of Merlin
    Wallace Ip; Fiscal Year: 2005
    ..We anticipate that these studies will shed new light on pathways involved in merlin-mediated tumor suppression, and may suggest possible molecular targets for therapeutic strategies for tumors that arise from loss of merlin function. ..
  62. Merlin Signal in Glioma: Therapeutic Agents and Targets
    Qin Yu; Fiscal Year: 2009
    ..Therefore, this proposal has high biological and clinical relevance ..
  63. Merlin Signal in Glioma: Therapeutic Agents and Targets
    Qin Yu; Fiscal Year: 2010
    ..Therefore, this proposal has high biological and clinical relevance ..
  64. NF2 BINDING PROTEINS
    Stefan Pulst; Fiscal Year: 1999
    ..Based on nucleolar localization of schwannomin in STS26T Schwann cells, its effect on RNA polymerase I transcription will be assayed in vitro using nuclear extracts, purified transcription factors and recombinant proteins. ..
  65. NF2 BINDING PROTEINS
    Stefan Pulst; Fiscal Year: 2000
    ..Based on nucleolar localization of schwannomin in STS26T Schwann cells, its effect on RNA polymerase I transcription will be assayed in vitro using nuclear extracts, purified transcription factors and recombinant proteins. ..
  66. NF2 BINDING PROTEINS
    Stefan Pulst; Fiscal Year: 1999
    ..Based on nucleolar localization of schwannomin in STS26T Schwann cells, its effect on RNA polymerase I transcription will be assayed in vitro using nuclear extracts, purified transcription factors and recombinant proteins. ..
  67. NF2 BINDING PROTEINS
    Stefan Pulst; Fiscal Year: 1999
    ..Based on nucleolar localization of schwannomin in STS26T Schwann cells, its effect on RNA polymerase I transcription will be assayed in vitro using nuclear extracts, purified transcription factors and recombinant proteins. ..
  68. FUNCTION OF MERLIN, A DROSOPHILA NF2 GENE HOMOLOGUE
    Richard Fehon; Fiscal Year: 2003
    ..Finally, these studies should contribute to work on the mechanisms by which cellular interactions function to control cell growth and determine cell fate during development. ..
  69. FUNCTION OF MERLIN, A DROSOPHILA NF2 GENE HOMOLOGUE
    Richard Fehon; Fiscal Year: 2005
    ..Finally, these studies should contribute to work on the mechanisms by which cellular interactions function to control cell growth and determine cell fate during development ..
  70. FUNCTION OF MERLIN, A DROSOPHILA NF2 GENE HOMOLOGUE
    Richard Fehon; Fiscal Year: 2004
    ..Finally, these studies should contribute to work on the mechanisms by which cellular interactions function to control cell growth and determine cell fate during development ..
  71. FUNCTION OF MERLIN, A DROSOPHILA NF2 GENE HOMOLOGUE
    Richard Fehon; Fiscal Year: 2009
    ..Finally, these studies should contribute to work on the mechanisms by which cellular interactions function to control cell growth and determine cell fate during development ..
  72. FUNCTION OF MERLIN, A DROSOPHILA NF2 GENE HOMOLOGUE
    Richard Fehon; Fiscal Year: 1999
    ..Finally, these studies should contribute to work on the mechanisms by which cellular interactions function to control cell growth and determine cell fate during development. ..
  73. A Manual Standup Wheelchair
    Steve Green; Fiscal Year: 2009
    ....
  74. FUNCTION OF MERLIN, A DROSOPHILA NF2 GENE HOMOLOGUE
    Richard Fehon; Fiscal Year: 2002
    ..Finally, these studies should contribute to work on the mechanisms by which cellular interactions function to control cell growth and determine cell fate during development. ..
  75. FUNCTION OF MERLIN, A DROSOPHILA NF2 GENE HOMOLOGUE
    Richard Fehon; Fiscal Year: 2000
    ..Finally, these studies should contribute to work on the mechanisms by which cellular interactions function to control cell growth and determine cell fate during development. ..
  76. FUNCTION OF MERLIN, A DROSOPHILA NF2 GENE HOMOLOGUE
    Richard Fehon; Fiscal Year: 2006
    ..Finally, these studies should contribute to work on the mechanisms by which cellular interactions function to control cell growth and determine cell fate during development ..
  77. Transcriptional regulation of growth downstream of tumor suppressor pathways
    Hyangyee Oh; Fiscal Year: 2007
    ....
  78. FUNCTION OF MERLIN, A DROSOPHILA NF2 GENE HOMOLOGUE
    Richard Fehon; Fiscal Year: 1999
    ..Finally, these studies should contribute to work on the mechanisms by which cellular interactions function to control cell growth and determine cell fate during development. ..
  79. FUNCTION OF MERLIN, A DROSOPHILA NF2 GENE HOMOLOGUE
    Richard Fehon; Fiscal Year: 2007
    ..Finally, these studies should contribute to work on the mechanisms by which cellular interactions function to control cell growth and determine cell fate during development ..
  80. Transcriptional regulation of growth downstream of tumor suppressor pathways
    Hyangyee Oh; Fiscal Year: 2009
    ....
  81. A Manual Standup Wheelchair
    Steve Green; Fiscal Year: 2010
    ....
  82. FUNCTION OF MERLIN, A DROSOPHILA NF2 GENE HOMOLOGUE
    Richard Fehon; Fiscal Year: 2001
    ..Finally, these studies should contribute to work on the mechanisms by which cellular interactions function to control cell growth and determine cell fate during development. ..
  83. Fine mapping 8q24 in Familial Bipolar Disorder
    Melvin McInnis; Fiscal Year: 2007
    ..With the identification, replication and characterization of the association for BP and 8q24 we will be in a strong positionto pursue further gene and functional studies. ..
  84. Fine mapping 8q24 in Familial Bipolar Disorder
    Melvin McInnis; Fiscal Year: 2005
    ..With the identification, replication and characterization of the association for BP and 8q24 we will be in a strong positionto pursue further gene and functional studies. ..
  85. Elucidation of NF2's tumor supressive function
    Chunling Yi; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  86. The NF2 gene: elucidation of tumor suppressor function
    JOSEPH KISSIL; Fiscal Year: 2004
    ..This should lead to a better understanding of merlin function in normal cells and the consequences of its loss in tumor development. Such information will directly assist in the search for effective therapies. ..
  87. Elucidation of NF2's tumor supressive function
    Chunling Yi; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable] [unreadable]..