protein isoforms

Summary

Summary: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing.

Top Publications

  1. ncbi Rocks: multifunctional kinases in cell behaviour
    Kirsi Riento
    Ludwig Institute for Cancer Research, Royal Free and University College School of Medicine, 91 Riding House Street, London W1W 7BS, UK
    Nat Rev Mol Cell Biol 4:446-56. 2003
  2. pmc Alternative isoform regulation in human tissue transcriptomes
    Eric T Wang
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nature 456:470-6. 2008
  3. pmc Analysis and design of RNA sequencing experiments for identifying isoform regulation
    Yarden Katz
    Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology MIT, Cambridge, Massachusetts, USA
    Nat Methods 7:1009-15. 2010
  4. pmc Statistical inferences for isoform expression in RNA-Seq
    Hui Jiang
    Institute for Computational and Mathematical Engineering and Department of Statistics, Stanford University, Stanford, CA 94305, USA
    Bioinformatics 25:1026-32. 2009
  5. ncbi The biology of VEGF and its receptors
    Napoleone Ferrara
    Department of Molecular Oncology, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nat Med 9:669-76. 2003
  6. pmc Genome-wide mapping of alternative splicing in Arabidopsis thaliana
    Sergei A Filichkin
    Department of Botany and Plant Pathology and Center for Genome Research and Biocomputing, Oregon State University, Corvallis, Oregon 97331, USA
    Genome Res 20:45-58. 2010
  7. pmc CCAAT/enhancer-binding proteins: structure, function and regulation
    Dipak P Ramji
    Cardiff School of Biosciences, Cardiff University, Museum Avenue, P O Box 911, Cardiff CF10 3US, Wales, U K
    Biochem J 365:561-75. 2002
  8. ncbi Apolipoprotein E: far more than a lipid transport protein
    R W Mahley
    Gladstone Institute of Cardiovascular Disease, University of California at San Francisco, San Francisco, California 94141 9100, USA
    Annu Rev Genomics Hum Genet 1:507-37. 2000
  9. ncbi The cytoplasmic body component TRIM5alpha restricts HIV-1 infection in Old World monkeys
    Matthew Stremlau
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 427:848-53. 2004
  10. ncbi Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy
    R S Savkur
    Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, USA
    Nat Genet 29:40-7. 2001

Research Grants

  1. Proteomics for Testing Hypotheses about Down Syndrome
    David Patterson; Fiscal Year: 2007
  2. GENETIC ANALYSIS OF POLARITY
    RUTH M STEWARD; Fiscal Year: 2010
  3. BIOCHEMISTRY OF PRE-MRNA SPLICING
    Adrian R Krainer; Fiscal Year: 2010
  4. Genetic &Functional Analyses of Hypertension Susceptibility Genes
    YEN PEI CHRISTY CHANG; Fiscal Year: 2013
  5. Functional characterization of the Bronx waltzer deafness gene
    Botond Banfi; Fiscal Year: 2013
  6. Nuclear Function of Abl in DNA Damage Response
    Jean Y J Wang; Fiscal Year: 2012
  7. Expression control in Drosophila splicing assembly factor RNP-4F
    JACK VAUGHN; Fiscal Year: 2010
  8. Cellular Mechanisms of Lymphatic Muscle Contractility
    MICHAEL JOHN DAVIS; Fiscal Year: 2012
  9. Role of LHX3 Protein Isoforms in Pituitary Development
    SIMON JAMES RHODES; Fiscal Year: 2012
  10. Role of Splicing Factors in Breast Cancer
    OLGA ANCZUKOW-CAMARDA; Fiscal Year: 2013

Detail Information

Publications309 found, 100 shown here

  1. ncbi Rocks: multifunctional kinases in cell behaviour
    Kirsi Riento
    Ludwig Institute for Cancer Research, Royal Free and University College School of Medicine, 91 Riding House Street, London W1W 7BS, UK
    Nat Rev Mol Cell Biol 4:446-56. 2003
    ..Recent experiments have defined new functions of ROCKs in cells, including centrosome positioning and cell-size regulation, which might contribute to various physiological and pathological states...
  2. pmc Alternative isoform regulation in human tissue transcriptomes
    Eric T Wang
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nature 456:470-6. 2008
    ..alternative processing of pre-messenger RNAs, individual mammalian genes often produce multiple mRNA and protein isoforms that may have related, distinct or even opposing functions...
  3. pmc Analysis and design of RNA sequencing experiments for identifying isoform regulation
    Yarden Katz
    Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology MIT, Cambridge, Massachusetts, USA
    Nat Methods 7:1009-15. 2010
    ..Our results provide a probabilistic framework for RNA-seq analysis, give functional insights into pre-mRNA processing and yield guidelines for the optimal design of RNA-seq experiments for studies of gene and isoform expression...
  4. pmc Statistical inferences for isoform expression in RNA-Seq
    Hui Jiang
    Institute for Computational and Mathematical Engineering and Department of Statistics, Stanford University, Stanford, CA 94305, USA
    Bioinformatics 25:1026-32. 2009
    ..Our results show that isoform expression inference in RNA-Seq is possible by employing appropriate statistical methods...
  5. ncbi The biology of VEGF and its receptors
    Napoleone Ferrara
    Department of Molecular Oncology, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nat Med 9:669-76. 2003
    ..VEGF inhibition is also being tested as a strategy for the prevention of angiogenesis, vascular leakage and visual loss in age-related macular degeneration...
  6. pmc Genome-wide mapping of alternative splicing in Arabidopsis thaliana
    Sergei A Filichkin
    Department of Botany and Plant Pathology and Center for Genome Research and Biocomputing, Oregon State University, Corvallis, Oregon 97331, USA
    Genome Res 20:45-58. 2010
    ..Taken together, our results suggest that like in animals, NMD and RUST may be widespread in plants and may play important roles in regulating gene expression...
  7. pmc CCAAT/enhancer-binding proteins: structure, function and regulation
    Dipak P Ramji
    Cardiff School of Biosciences, Cardiff University, Museum Avenue, P O Box 911, Cardiff CF10 3US, Wales, U K
    Biochem J 365:561-75. 2002
    ..This review deals with the structure, biological function and the regulation of the C/EBP family...
  8. ncbi Apolipoprotein E: far more than a lipid transport protein
    R W Mahley
    Gladstone Institute of Cardiovascular Disease, University of California at San Francisco, San Francisco, California 94141 9100, USA
    Annu Rev Genomics Hum Genet 1:507-37. 2000
    ..Functional differences in the apoE isoforms that affect (or did affect) survival before the reproductive years probably account, at least in part, for the allele frequencies of the present day...
  9. ncbi The cytoplasmic body component TRIM5alpha restricts HIV-1 infection in Old World monkeys
    Matthew Stremlau
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 427:848-53. 2004
    ..Our studies identify TRIM5alpha as a species-specific mediator of innate cellular resistance to HIV-1 and reveal host cell components that modulate the uncoating of a retroviral capsid...
  10. ncbi Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy
    R S Savkur
    Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, USA
    Nat Genet 29:40-7. 2001
    ..These results support a model in which increased expression of a splicing regulator contributes to insulin resistance in DM1 by affecting IR alternative splicing...
  11. ncbi Estrogen receptors: how do they signal and what are their targets
    Nina Heldring
    Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
    Physiol Rev 87:905-31. 2007
    ..In this review we focus on several of the interesting recent discoveries concerning estrogen receptors, on estrogen as a morphogen, and on the molecular mechanisms of anti-estrogen signaling...
  12. pmc Mapping intact protein isoforms in discovery mode using top-down proteomics
    John C Tran
    Department of Chemistry and Biochemistry, and the Institute for Genomic Biology, University of Illinois at Urbana Champaign, Urbana, Illinois 61801, USA
    Nature 480:254-8. 2011
    ..and endogenous protein cleavages, especially when combinations of these create complex patterns of intact protein isoforms and species...
  13. pmc Spatially restricted patterning cues provided by heparin-binding VEGF-A control blood vessel branching morphogenesis
    Christiana Ruhrberg
    Endothelial Cell Biology Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, United Kingdom
    Genes Dev 16:2684-98. 2002
    ..We conclude that differential VEGF-A isoform localization in the extracellular space provides a control point for regulating vascular branching pattern...
  14. pmc Neurexin-neuroligin signaling in synapse development
    Ann Marie Craig
    Brain Research Centre, University of British Columbia, 2211 Wesbrook Mall, Vancouver V6T 2B5, Canada
    Curr Opin Neurobiol 17:43-52. 2007
    ....
  15. ncbi CD44, a therapeutic target for metastasising tumours
    Veronique Orian-Rousseau
    Karlsruhe Institute of Technology, Institute for Toxicology and Genetics, Hermann von Helmholtzplatz 1, 76344 Eggenstein Leopoldshafen, Germany
    Eur J Cancer 46:1271-7. 2010
    ..Other peptides block RTK activation and thereby inhibit tumour angiogenesis and metastatic spread...
  16. pmc UTRdb and UTRsite (RELEASE 2010): a collection of sequences and regulatory motifs of the untranslated regions of eukaryotic mRNAs
    Giorgio Grillo
    Istituto Tecnologie Biomediche del Consiglio Nazionale delle Ricerche, Via Amendola 122 D, 70126 Bari, Italy
    Nucleic Acids Res 38:D75-80. 2010
    ..All internet resources implemented for retrieval and functional analysis of 5' and 3' untranslated regions of eukaryotic mRNAs are accessible at http://utrdb.ba.itb.cnr.it/...
  17. 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...
  18. ncbi Akt1/PKBalpha is required for normal growth but dispensable for maintenance of glucose homeostasis in mice
    H Cho
    Department of Biology, University of Pennsylvania, Philadelphia 19104, USA
    J Biol Chem 276:38349-52. 2001
    ....
  19. ncbi Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle
    A Musaro
    Cardiovascular Research Center, Massachusetts General Hospital East, Charlestown, Massachusetts, USA
    Nat Genet 27:195-200. 2001
    ..The preservation of muscle architecture and age-independent regenerative capacity through localized mIgf-1 transgene expression suggests clinical strategies for the treatment of age or disease-related muscle frailty...
  20. pmc A novel androgen receptor splice variant is up-regulated during prostate cancer progression and promotes androgen depletion-resistant growth
    Zhiyong Guo
    Department of Pharmacology and Experimental Therapeutics and The Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA
    Cancer Res 69:2305-13. 2009
    ..Given that these novel AR splice variants are not inhibited by currently available antiandrogen drugs, development of new drugs targeting these AR isoforms may potentially be effective for treatment of ablation-resistant PCA...
  21. ncbi How do they do Wnt they do?: regulation of transcription by the Wnt/β-catenin pathway
    H C Archbold
    Program in Cell and Molecular Biology, University of Michigan, Ann Arbor, 48109 1048, USA
    Acta Physiol (Oxf) 204:74-109. 2012
    ....
  22. ncbi GFAP in health and disease
    J Middeldorp
    Department of Astrocyte Biology and Neurodegeneration, Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands
    Prog Neurobiol 93:421-43. 2011
    ..In this review we discuss the versatility of the GFAP cytoskeletal network from gene to function with a focus on astrocytes during human brain development, aging and disease...
  23. 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...
  24. pmc p53 directly transactivates Δ133p53α, regulating cell fate outcome in response to DNA damage
    M Aoubala
    Centre for Oncology and Molecular Medicine, Inserm European Associated Laboratory U858, University of Dundee, College of Medicine, Dundee, UK
    Cell Death Differ 18:248-58. 2011
    ..Therefore, endogenous Δ133p53α does not exclusively function in a dominant-negative manner toward p53, but differentially regulates cell cycle arrest and apoptosis...
  25. pmc ESRP1 and ESRP2 are epithelial cell-type-specific regulators of FGFR2 splicing
    Claude C Warzecha
    Department of Medicine, Renal Division, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Mol Cell 33:591-601. 2009
    ..These studies suggest that Epithelial Splicing Regulatory Proteins 1 and 2 (ESRP1 and ESRP2) are coordinators of an epithelial cell-type-specific splicing program...
  26. ncbi Genome-wide analyses of alternative splicing in plants: opportunities and challenges
    W Brad Barbazuk
    Donald Danforth Plant Science Center, St Louis, Missouri 63132, USA
    Genome Res 18:1381-92. 2008
    ..This review summarizes recent analyses of AS in plants, discusses the importance of further analysis, and suggests directions for future efforts...
  27. pmc Distinct roles of Akt1 and Akt2 in regulating cell migration and epithelial-mesenchymal transition
    Hanna Y Irie
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    J Cell Biol 171:1023-34. 2005
    ..These results highlight the distinct functions of Akt isoforms in regulating growth factor-stimulated EMT and cell migration, as well as the importance of Akt1 in cross-regulating the ERK signaling pathway...
  28. pmc Biological functions of p53 isoforms through evolution: lessons from animal and cellular models
    V Marcel
    Centre for Oncology and Molecular Medicine, Inserm European Associated Laboratory, University of Dundee, Ninewells Hospital, Dundee, Scotland, UK
    Cell Death Differ 18:1815-24. 2011
    The TP53 tumour-suppressor gene is expressed as several protein isoforms generated by different mechanisms, including use of alternative promoters, splicing sites and translational initiation sites, that are conserved through evolution ..
  29. ncbi A muscleblind knockout model for myotonic dystrophy
    Rahul N Kanadia
    Department of Molecular Genetics and Microbiology, Powell Gene Therapy Center, Gainesville, FL 32610, USA
    Science 302:1978-80. 2003
    ..Our results support the hypothesis that manifestations of DM can result from sequestration of specific RNA binding proteins by a repetitive element expansion in a mutant RNA...
  30. pmc Stochastic noise in splicing machinery
    Eugene Melamud
    Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, 9600 Gudelsky Drive, Rockville, MD 20850, USA
    Nucleic Acids Res 37:4873-86. 2009
    ..Based on simulation of sampling of virtual cDNA libraries, we estimate that error rates range from 1 to 10% depending on the number of introns and the expression level of a gene...
  31. ncbi p53/p63/p73 isoforms: an orchestra of isoforms to harmonise cell differentiation and response to stress
    F Murray-Zmijewski
    Department of Surgery and Molecular Oncology, University of Dundee, Ninewells Hospital, CR UK Cell Transformation Research Group, Dundee DD19SY, UK
    Cell Death Differ 13:962-72. 2006
    ..The changes in the interactions between p53, p63 and p73 isoforms are likely to be fundamental to our understanding in the transition between normal cell cycling and the onset of tumour formation...
  32. ncbi Distinct functions of the two isoforms of dopamine D2 receptors
    A Usiello
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS, INSERM, ULP, Illkirch, C U de Strasbourg, France
    Nature 408:199-203. 2000
    ..The absence of D2L reveals that D2S inhibits D1 receptor-mediated functions, uncovering a circuit of signalling interference between dopamine receptors...
  33. ncbi 14-3-3 proteins: a historic overview
    Alastair Aitken
    University of Edinburgh, School of Biological Sciences, Kings Buildings, Scotland, UK
    Semin Cancer Biol 16:162-72. 2006
    ....
  34. ncbi p63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis
    James W Rocco
    Massachusetts General Hospital Center for Cancer Research and Harvard Medical School, Boston, Massachusetts 02114, USA
    Cancer Cell 9:45-56. 2006
    ..Together, these data define a pathway whereby deltaNp63alpha promotes survival in squamous epithelial malignancy by repressing a p73-dependent proapoptotic transcriptional program...
  35. ncbi Alternative splicing: new insights from global analyses
    Benjamin J Blencowe
    Banting and Best Department of Medical Research and Department of Molecular and Medical Genetics, Centre for Cellular and Biomolecular Research, Donnelly CCBR Building, University of Toronto, Toronto, ON M5S 3E1, Canada
    Cell 126:37-47. 2006
    ..Recent progress in these areas is summarized in this review...
  36. pmc Splicing of a novel androgen receptor exon generates a constitutively active androgen receptor that mediates prostate cancer therapy resistance
    Scott M Dehm
    Department of Urology and Biochemistry, Mayo Clinical College of Medicine, Rochester, Minnesota, USA
    Cancer Res 68:5469-77. 2008
    ..Together, our data describe a simple and effective mechanism by which PCa cells can synthesize a constitutively active AR and thus circumvent androgen ablation...
  37. pmc Alternative splicing in concert with protein intrinsic disorder enables increased functional diversity in multicellular organisms
    Pedro R Romero
    School of Informatics, Indiana University Purdue University Indianapolis, 535 West Michigan Street, IT475, Indianapolis, IN 46202, USA
    Proc Natl Acad Sci U S A 103:8390-5. 2006
    Alternative splicing of pre-mRNA generates two or more protein isoforms from a single gene, thereby contributing to protein diversity...
  38. pmc p53 isoforms can regulate p53 transcriptional activity
    Jean Christophe Bourdon
    Department of Surgery, Cancer Research UK Cell Transformation Research Group, University of Dundee, Ninewells Hospital, Scotland, UK
    Genes Dev 19:2122-37. 2005
    ..The differential expression of the p53 isoforms in human tumors may explain the difficulties in linking p53 status to the biological properties and drug sensitivity of human cancer...
  39. pmc Bromodomain protein Brd4 associated with acetylated chromatin is important for maintenance of higher-order chromatin structure
    Ranran Wang
    Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 287:10738-52. 2012
    ..These studies establish a novel structural role of Brd4 in supporting the higher chromatin architecture...
  40. pmc Human SMG-1, a novel phosphatidylinositol 3-kinase-related protein kinase, associates with components of the mRNA surveillance complex and is involved in the regulation of nonsense-mediated mRNA decay
    A Yamashita
    Department of Molecular Biology, Yokohama City University School of Medicine, Yokohama 236 0004, Japan
    Genes Dev 15:2215-28. 2001
    ..Taken together, we conclude that hSMG-1 plays a critical role in NMD through the direct phosphorylation of hUPF1/SMG-2 in the evolutionally conserved mRNA surveillance complex...
  41. pmc Prediction of alternative isoforms from exon expression levels in RNA-Seq experiments
    Hugues Richard
    Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Ihnestr 73, 14195 Berlin, Germany
    Nucleic Acids Res 38:e112. 2010
    ..The software is available as an open-source R-package called Solas at http://cmb.molgen.mpg.de/2ndGenerationSequencing/Solas/...
  42. ncbi CD44 in cancer progression: adhesion, migration and growth regulation
    R Marhaba
    Department of Tumor Progression and Immune Defense, German Cancer Research Center, D 69120 Heidelberg, Germany
    J Mol Histol 35:211-31. 2004
    ....
  43. pmc Exon-level microarray analyses identify alternative splicing programs in breast cancer
    Anna Lapuk
    Life Sciences Division, Lawrence Berkeley National Laboratory, University of California at Berkeley, Berkeley, California 94720, USA
    Mol Cancer Res 8:961-74. 2010
    b>Protein isoforms produced by alternative splicing (AS) of many genes have been implicated in several aspects of cancer genesis and progression. These observations motivated a genome-wide assessment of AS in breast cancer...
  44. ncbi p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities
    A Yang
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 2:305-16. 1998
    ..We demonstrate that these truncated p63 variants can act as dominant-negative agents toward transactivation by p53 and p63, and we suggest the possibility of physiological interactions among members of the p53 family...
  45. ncbi Neuregulins: functions, forms, and signaling strategies
    Douglas L Falls
    Center for Neurodegenerative Disease, Department of Neurology, Emory University, Atlanta, GA 30322, USA
    Exp Cell Res 284:14-30. 2003
    ....
  46. pmc GFAP isoforms in adult mouse brain with a focus on neurogenic astrocytes and reactive astrogliosis in mouse models of Alzheimer disease
    Willem Kamphuis
    Netherlands Institute for Neuroscience an Institute of the Royal Netherlands Academy of Arts and Sciences, Department of Astrocyte Biology and Neurodegeneration, Amsterdam, The Netherlands
    PLoS ONE 7:e42823. 2012
    ..This evidence points to the conclusion that differential regulation of GFAP isoforms is not involved in the reorganization of the IF network in reactive gliosis or in neurogenesis in the mouse brain...
  47. pmc ΔNp63 knockout mice reveal its indispensable role as a master regulator of epithelial development and differentiation
    Rose Anne Romano
    Department of Biochemistry, Center for Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, NY 14203, USA
    Development 139:772-82. 2012
    ....
  48. pmc Muscle expression of a local Igf-1 isoform protects motor neurons in an ALS mouse model
    Gabriella Dobrowolny
    Department of Histology and Medical Embryology, CE BEMM and Interuniversity Institute of Myology, University of Rome La Sapienza, 14 00161 Rome, Italy
    J Cell Biol 168:193-9. 2005
    ..These studies establish skeletal muscle as a primary target for the dominant action of inherited SOD1 mutation and suggest that muscle fibers provide appropriate factors, such as mIgf-1, for neuron survival...
  49. pmc Analysis of alternative splicing associated with aging and neurodegeneration in the human brain
    James R Tollervey
    MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom
    Genome Res 21:1572-82. 2011
    ..In conclusion, the alternative splicing changes identified in this study provide a new link between aging and neurodegeneration...
  50. ncbi PML protein isoforms and the RBCC/TRIM motif
    K Jensen
    Centre for Structural Biology, Imperial College of Science, Technology and Medicine, Flowers Building, Armstrong Road, London SW7 2AZ, UK
    Oncogene 20:7223-33. 2001
    ..In APL oligomerization mediated by the RBCC/TRIM motif is essential for the transformation potential of the PML-RARalpha fusion protein...
  51. pmc The C-terminus of p63 contains multiple regulatory elements with different functions
    W E Straub
    Institute of Biophysical Chemistry, Goethe University, Frankfurt am Main, Germany
    Cell Death Dis 1:e5. 2010
    ..We therefore propose that the inhibitory function of the C-terminal domain is in part due to direct inhibition of the transcriptional activity of the protein and in part due to indirect inhibition by controlling the concentration of p63...
  52. pmc Global changes in processing of mRNA 3' untranslated regions characterize clinically distinct cancer subtypes
    Priyam Singh
    The Jackson Laboratory, Bar Harbor, Maine 04609, USA
    Cancer Res 69:9422-30. 2009
    ..Finally, these findings provide insights into the molecular mechanisms of gene deregulation in tumorigenesis...
  53. ncbi The ubiquitin-related BAG-1 provides a link between the molecular chaperones Hsc70/Hsp70 and the proteasome
    J Lüders
    Department of Molecular Cell Biology, Max Planck Institute for Biochemistry, Am Klopferspitz 18a, D 82152 Martinsried, Germany
    J Biol Chem 275:4613-7. 2000
    ..A regulatory function of the chaperone cofactor at the interface between protein folding and protein degradation is thus indicated...
  54. pmc Distinct roles of septins in cytokinesis: SEPT9 mediates midbody abscission
    Mathew P Estey
    Program in Cell Biology, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
    J Cell Biol 191:741-9. 2010
    ..We demonstrate that SEPT9 mediates the localization of the vesicle-tethering exocyst complex to the midbody, providing mechanistic insight into the role of SEPT9 during abscission...
  55. pmc Translational control of C/EBPalpha and C/EBPbeta isoform expression
    C F Calkhoven
    Max Delbruck Center for Molecular Medicine, 13092 Berlin, Germany
    Genes Dev 14:1920-32. 2000
    ..Our results demonstrate that the translational controlled ratio of C/EBPalpha and C/EBPbeta isoform expression determines cell fate...
  56. pmc Regulation of TMEM16A chloride channel properties by alternative splicing
    Loretta Ferrera
    Laboratory of Molecular Genetics, Istituto Giannina Gaslini, Largo G Gaslini 5, 16147 Genova
    J Biol Chem 284:33360-8. 2009
    ..Alternative splicing appears as an important mechanism to regulate the voltage and Ca(2+) dependence of the TMEM16A-dependent Cl(-) channels in a tissue-specific manner...
  57. pmc Regulation of vascular endothelial growth factor (VEGF) splicing from pro-angiogenic to anti-angiogenic isoforms: a novel therapeutic strategy for angiogenesis
    Dawid G Nowak
    Microvascular Research Laboratories, Bristol Heart Institute, Department of Physiology and Pharmacology, School of Veterinary Sciences, University of Bristol, Bristol BS2 8EJ, United Kingdom
    J Biol Chem 285:5532-40. 2010
    ..Injection of an SRPK1/2 inhibitor reduced angiogenesis in a mouse model of retinal neovascularization, suggesting that regulation of alternative splicing could be a potential therapeutic strategy in angiogenic pathologies...
  58. pmc A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis
    Ulrike Philippar
    Massachusetts Institute of Technology, Koch Institute, Cambridge, MA 02139, USA
    Dev Cell 15:813-28. 2008
    ..Upregulation of Mena(INV) could therefore enable tumor cells to invade in response to otherwise benign EGF stimulus levels...
  59. ncbi Short- and long-range attraction of cortical GABAergic interneurons by neuregulin-1
    Nuria Flames
    Instituto de Neurociencias de Alicante, Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández, 03550 San Joan d Alacant, Spain
    Neuron 44:251-61. 2004
    ..These observations provide evidence that Neuregulin-1 and its ErbB4 receptor directly control neuronal migration in the nervous system...
  60. pmc Isoform-specific p73 knockout mice reveal a novel role for delta Np73 in the DNA damage response pathway
    Margareta T Wilhelm
    The Campbell Family Institute for Breast Cancer Research, Princess Margaret Hospital, Toronto, Ontario, Canada
    Genes Dev 24:549-60. 2010
    ..This novel finding may explain why human tumors with high levels of DeltaNp73 expression show enhanced resistance to chemotherapy...
  61. ncbi c-FLIPR, a new regulator of death receptor-induced apoptosis
    Alexander Golks
    Division of Immunogenetics, Tumorimmunology Program, German Cancer Research Center, Im Neuenheimer Feld 280, D 69120 Heidelberg, Germany
    J Biol Chem 280:14507-13. 2005
    ..Taken together, our data demonstrate endogenous expression of c-FLIP(R) and similar roles of c-FLIP(R) and c-FLIP(S) isoforms in death receptor-mediated apoptosis...
  62. ncbi Cellular signaling by fibroblast growth factor receptors
    V P Eswarakumar
    Yale University School of Medicine, Department of Pharmacology, 333 Cedar Street, P O Box 208066, SHM B 295, New Haven, CT 06520, USA
    Cytokine Growth Factor Rev 16:139-49. 2005
    ....
  63. pmc MURC/Cavin-4 and cavin family members form tissue-specific caveolar complexes
    Michele Bastiani
    Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia
    J Cell Biol 185:1259-73. 2009
    ..Cavin-4 is expressed predominantly in muscle, and its distribution is perturbed in human muscle disease associated with Caveolin-3 dysfunction, identifying Cavin-4 as a novel muscle disease candidate caveolar protein...
  64. ncbi The human OCT-4 isoforms differ in their ability to confer self-renewal
    Jungwoon Lee
    Laboratory of Molecular and Cellular Biology, Department of Life Science, Sogang University, Seoul 121 742, Korea
    J Biol Chem 281:33554-65. 2006
    ..Taken together, these data suggest that the DNA binding, transactivation, and abilities to confer self-renewal of the human OCT-4 isoforms differ...
  65. pmc Expression of pro- and anti-angiogenic isoforms of VEGF is differentially regulated by splicing and growth factors
    Dawid G Nowak
    Microvascular Research Laboratories, Bristol Heart Institute, Department of Physiology and Pharmacology, School of Veterinary Sciences, University of Bristol, Southwell Street, Bristol BS2 8EJ, UK
    J Cell Sci 121:3487-95. 2008
    ....
  66. pmc Loss of function of def selectively up-regulates Delta113p53 expression to arrest expansion growth of digestive organs in zebrafish
    Jun Chen
    Laboratory of Functional Genomics, Laboratory of Molecular and Developmental Immunology, Laboratory of Control of p53 Pathway, Institute of Molecular and Cell Biology, Proteos, Singapore 138673
    Genes Dev 19:2900-11. 2005
    ....
  67. pmc Comparative proteomics reveals a significant bias toward alternative protein isoforms with conserved structure and function
    Iakes Ezkurdia
    Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre, Madrid, Spain
    Mol Biol Evol 29:2265-83. 2012
    ..We provide a detailed overview of the population of alternatively spliced protein isoforms that are detectable by peptide identification methods...
  68. pmc Functional analyses of the plant photosystem I-light-harvesting complex II supercomplex reveal that light-harvesting complex II loosely bound to photosystem II is a very efficient antenna for photosystem I in state II
    Pierre Galka
    Aix Marseille Universite, Biologie Végétale et Microbiologie Environementales, Laboratoire de Genetique et Biophysique des Plantes, 13288 Marseille, France
    Plant Cell 24:2963-78. 2012
    ..In contrast with the common opinion, we suggest that the mobile pool of LHCII may be considered an intimate part of the PSI antenna system that is displaced to PSII in State I...
  69. pmc A subset of tumor-derived mutant forms of p53 down-regulate p63 and p73 through a direct interaction with the p53 core domain
    C Gaiddon
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Mol Cell Biol 21:1874-87. 2001
    ....
  70. pmc Anchorage of VEGF to the extracellular matrix conveys differential signaling responses to endothelial cells
    Tom T Chen
    Department of Molecular, Cellular, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA
    J Cell Biol 188:595-609. 2010
    ....
  71. pmc Regulation of human p53 activity and cell localization by alternative splicing
    Anirban Ghosh
    Department of Microbiology and Immunology, McGill University, 3775 University St, Room 511, Montreal, Quebec, Canada H3A 2B4
    Mol Cell Biol 24:7987-97. 2004
    ..The expression of p47 through alternative splicing of the p53 gene thus has a major influence over p53 activity at least in part through controlling p53 ubiquitination and cell localization...
  72. ncbi Immunochemical and mass-spectrometry-based serum hepcidin assays for iron metabolism disorders
    Joyce J C Kroot
    Laboratory of Genetic, Endocrine and Metabolic Diseases, Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Clin Chem 56:1570-9. 2010
    ..Hepcidin is instrumental in the diagnosis and monitoring of iron metabolism disorders, but reliable methods for its quantification in serum are sparse, as is knowledge of their relative analytical strengths and clinical utility...
  73. ncbi Hyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms
    Cathy Andorfer
    Departments of Neuroscience and Pathology, Albert Einstein College of Medicine, Bronx, New York, USA
    J Neurochem 86:582-90. 2003
    ..This pathologic tau accumulates in the cell bodies and dendrites of neurons in a spatiotemporally relevant distribution...
  74. pmc Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKB beta
    Robert S Garofalo
    Pfizer Global Research and Development, Groton, Connecticut 06357, USA
    J Clin Invest 112:197-208. 2003
    ....
  75. ncbi SynCAMs organize synapses through heterophilic adhesion
    Adam I Fogel
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA
    J Neurosci 27:12516-30. 2007
    ..Our results define SynCAM proteins as components of novel heterophilic transsynaptic adhesion complexes that set up asymmetric interactions, with SynCAM proteins contributing to synapse organization and function...
  76. ncbi The PDGF family: four gene products form five dimeric isoforms
    Linda Fredriksson
    Ludwig Institute for Cancer Research, Stockholm Branch, Box 240, S 171 77 Stockholm, Sweden
    Cytokine Growth Factor Rev 15:197-204. 2004
    ..The discovery of two additional ligands for the two PDGF receptors suggests that PDGF-mediated cellular signaling is more complex than previously thought...
  77. ncbi Tau protein isoforms, phosphorylation and role in neurodegenerative disorders
    L Buee
    INSERM U422, Place de Verdun, 59045 Cedex, Lille, France
    Brain Res Brain Res Rev 33:95-130. 2000
    ....
  78. ncbi OCT4 spliced variants are differentially expressed in human pluripotent and nonpluripotent cells
    Yaser Atlasi
    Department of Genetics, Faculty of Basic Sciences, Tarbiat Modares University, Tehran, Iran
    Stem Cells 26:3068-74. 2008
    ....
  79. ncbi Requirements for the localization of nesprin-3 at the nuclear envelope and its interaction with plectin
    Mirjam Ketema
    Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    J Cell Sci 120:3384-94. 2007
    ..Our studies support a model in which the actin cytoskeleton influences the binding of plectin dimers to dimers of nesprin-3alpha, which in turn are retained at the nuclear envelope through an interaction with Sun proteins...
  80. pmc Alternative splicing of Tcf7l2 transcripts generates protein variants with differential promoter-binding and transcriptional activation properties at Wnt/beta-catenin targets
    Andreas Weise
    Institute of Molecular Medicine and Cell Research, Center for Biochemistry and Molecular Cell Research, Spemann Graduate School of Biology and Medicine, Albert Ludwigs University Freiburg, Germany
    Nucleic Acids Res 38:1964-81. 2010
    ..Still, the cell-type-specific complement of TCF4 isoforms is likely to be a major determinant for the context-dependent transcriptional output of Wnt/beta-catenin signalling...
  81. ncbi mRNA-Seq whole-transcriptome analysis of a single cell
    Fuchou Tang
    Wellcome Trust Cancer Research UK Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Cambridge, UK
    Nat Methods 6:377-82. 2009
    ..Finally, for Dicer1(-/-) and Ago2(-/-) (Eif2c2(-/-)) oocytes, we found that 1,696 and 1,553 genes, respectively, were abnormally upregulated compared to wild-type controls, with 619 genes in common...
  82. pmc Plectin 1f scaffolding at the sarcolemma of dystrophic (mdx) muscle fibers through multiple interactions with beta-dystroglycan
    Günther A Rezniczek
    Max F Perutz Laboratories, Department of Molecular Cell Biology, University of Vienna, A 1030 Vienna, Austria
    J Cell Biol 176:965-77. 2007
    ..Alternative splicing of plectin transcripts gives rise to more than eight protein isoforms differing only in small N-terminal sequences (5-180 residues), four of which (plectins 1, 1b, 1d, and 1f) are ..
  83. ncbi Neurofilament phosphoforms: surrogate markers for axonal injury, degeneration and loss
    Axel Petzold
    Department of Neuroimmunology, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
    J Neurol Sci 233:183-98. 2005
    ..With reference to the present symposium on multiple sclerosis, the current literature on body fluid levels of neurofilaments in demyelinating disease is summarised...
  84. pmc Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors
    Sunyoung Lee
    Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles 90095, USA
    J Cell Biol 169:681-91. 2005
    ..Our findings support the view that matrix-bound VEGF and nontethered VEGF provide different signaling outcomes. These findings reveal a novel aspect in the regulation of extracellular VEGF that holds significance for vascular patterning...
  85. ncbi A novel gene for Usher syndrome type 2: mutations in the long isoform of whirlin are associated with retinitis pigmentosa and sensorineural hearing loss
    Inga Ebermann
    Institute of Human Genetics, University Hospital of Cologne, Kerpener Str 34, 50931 Cologne, Germany
    Hum Genet 121:203-11. 2007
    ..We describe a novel genetic subtype for Usher syndrome, which we named USH2D and which is caused by mutations in whirlin. Moreover, this is the first case of USH2 that is allelic to non-syndromic deafness...
  86. pmc PML isoforms I and II participate in PML-dependent restriction of HSV-1 replication
    Delphine Cuchet
    MRC University of Glasgow Centre for Virus Research, Church Street, Glasgow G11 5JR, Scotland, UK
    J Cell Sci 124:280-91. 2011
    ..Our observations suggest that complete functionality of PML is dependent on isoform-specific C-terminal sequences acting in concert...
  87. ncbi Myelin basic protein: a multifunctional protein
    J M Boggs
    Department of Structural Biology and Biochemistry, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada
    Cell Mol Life Sci 63:1945-61. 2006
    ..Further study of this very abundant protein will reveal how it is utilized by the oligodendrocyte and myelin for different purposes...
  88. pmc Myofiber integrity depends on desmin network targeting to Z-disks and costameres via distinct plectin isoforms
    Patryk Konieczny
    Max F Perutz Laboratories, Department of Molecular Cell Biology, University of Vienna, A 1030 Vienna, Austria
    J Cell Biol 181:667-81. 2008
    ..Our findings establish plectin as the major organizer of desmin IFs in myofibers and provide new insights into plectin- and desmin-related muscular dystrophies...
  89. pmc Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells
    F Frasca
    Istituto di Medicina Interna, Malattie Endocrine e del Metabolismo, University of Catania, Ospedale Garibaldi, 95123 Catania, Italy
    Mol Cell Biol 19:3278-88. 1999
    ..These data indicate, therefore, that there are two receptors for IGF-II, both IGF-I-R and IR-A. Further, they suggest that interaction of IGF-II with IR-A may play a role both in fetal growth and cancer biology...
  90. pmc Expression and function of epithelial anoctamins
    Rainer Schreiber
    Institut fur Physiologie, Universitat Regensburg, Universitatsstrasse 31, D 93053 Regensburg, Germany
    J Biol Chem 285:7838-45. 2010
    ..We conclude that each tissue expresses a set of anoctamins that form cell- and tissue-specific Ca(2+)-dependent Cl(-) channels...
  91. ncbi Requirement for a peptidoglycan recognition protein (PGRP) in Relish activation and antibacterial immune responses in Drosophila
    Kwang Min Choe
    Molecular Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Science 296:359-62. 2002
    ....
  92. ncbi The putative ovarian tumour marker gene HE4 (WFDC2), is expressed in normal tissues and undergoes complex alternative splicing to yield multiple protein isoforms
    Lynne Bingle
    Respiratory Medicine Unit, Division of Genomic Medicine, University of Sheffield Medical School, Sheffield S10 2RX, UK
    Oncogene 21:2768-73. 2002
    ..complex series of alternative splicing events that can potentially yield five distinct WAP domain containing protein isoforms. These results cast doubt on the potential role of HE4 as a serum tumour marker specific for ovarian cancer ..
  93. ncbi RNA editing at arg607 controls AMPA receptor exit from the endoplasmic reticulum
    Ingo H Greger
    Howard Hughes Medical Institute, Department of Biochemistry, NYU School of Medicine, New York 10016, USA
    Neuron 34:759-72. 2002
    ..Therefore, Arg607 is a central regulator. In addition to channel gating, it also controls ER exit and may thereby ensure the availability of GluR2 for assembly into AMPARs...
  94. pmc Deletion of the laminin alpha4 chain leads to impaired microvessel maturation
    Jill Thyboll
    Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S 17 177 Stockholm, Sweden
    Mol Cell Biol 22:1194-202. 2002
    ..The results demonstrate a central role for the laminin alpha4 chain in microvessel growth and, in the absence of other laminin alpha chains, in the composition of endothelial basement membranes...
  95. ncbi Structure of the glucocorticoid receptor (NR3C1) gene 5' untranslated region: identification, and tissue distribution of multiple new human exon 1
    Jonathan D Turner
    Institute of Immunology, Laboratoire National de Santé, 20A rue Auguste Lumière, L 1011, Luxembourg
    J Mol Endocrinol 35:283-92. 2005
    ..UTR) of the glucocorticoid receptor (GR) plays a key role in determining tissue-specific expression and protein isoforms. Analysis of the 5' UTR of the human GR (hGR) has revealed 11 splice variants of the hGR exon 1, based on ..
  96. ncbi Distinct roles of different neural cell adhesion molecule (NCAM) isoforms in synaptic maturation revealed by analysis of NCAM 180 kDa isoform-deficient mice
    Luis Polo-Parada
    Department of Neurosciences, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106 4975, USA
    J Neurosci 24:1852-64. 2004
    ..Together, these results indicate that different isoforms of NCAM mediate distinct and important events in presynaptic maturation...
  97. pmc TRIP8b splice variants form a family of auxiliary subunits that regulate gating and trafficking of HCN channels in the brain
    Bina Santoro
    Department of Neuroscience, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA
    Neuron 62:802-13. 2009
    ..TRIP8b thus functions as an auxiliary subunit that provides a mechanism for the dynamic regulation of HCN1 channel expression and function...
  98. pmc Tissue-specific alternative splicing of TCF7L2
    Ludmila Prokunina-Olsson
    Genome Technology Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA
    Hum Mol Genet 18:3795-804. 2009
    ..Alternative splicing of TCF7L2 in pancreatic islets warrants future studies. GenBank Accession Numbers: FJ010164-FJ010174...
  99. pmc The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth
    Tadahiro Kitamura
    Naomi Berrie Diabetes Center, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York, USA
    J Clin Invest 110:1839-47. 2002
    ..We propose that insulin/IGFs regulate beta cell proliferation by relieving Foxo1 inhibition of Pdx1 expression in a subset of cells embedded within pancreatic ducts...
  100. pmc Central functions of the lumenal and peripheral thylakoid proteome of Arabidopsis determined by experimentation and genome-wide prediction
    Jean Benoit Peltier
    Department of Plant Biology, Cornell University, Ithaca, New York 14853, USA
    Plant Cell 14:211-36. 2002
    ..Many of the predicted lumenal proteins must be present at concentrations at least 10,000-fold lower than proteins of the photosynthetic apparatus...
  101. ncbi Transient association of titin and myosin with microtubules in nascent myofibrils directed by the MURF2 RING-finger protein
    Véronique Pizon
    European Molecular Biology Laboratory, Cell Biology Division, Heidelberg, Germany
    J Cell Sci 115:4469-82. 2002
    ..MURF2 can therefore act as a transient adaptor between microtubules, titin and nascent myosin filaments, as well as being involved in signalling from the sarcomere to the nucleus...

Research Grants68

  1. Proteomics for Testing Hypotheses about Down Syndrome
    David Patterson; Fiscal Year: 2007
    ..A single gene frequently gives rise to multiple protein isoforms by posttranscriptional mechanisms, such as alternative splicing or posttranslational modifications...
  2. GENETIC ANALYSIS OF POLARITY
    RUTH M STEWARD; Fiscal Year: 2010
    ..transcript that gives rise to one protein;there are multiple human PDCD2 cDNAs, giving rise to at least two protein isoforms, differentially expressed both in normal and malignant human tissues...
  3. BIOCHEMISTRY OF PRE-MRNA SPLICING
    Adrian R Krainer; Fiscal Year: 2010
    ..Many genes express multiple mRNA and protein isoforms by alternative splicing of their primary transcripts...
  4. Genetic &Functional Analyses of Hypertension Susceptibility Genes
    YEN PEI CHRISTY CHANG; Fiscal Year: 2013
    ..We will validate and characterize transcript and protein isoforms of these kinases and co-transporters to obtain a better understanding of how they work together to regulate ..
  5. Functional characterization of the Bronx waltzer deafness gene
    Botond Banfi; Fiscal Year: 2013
    ..gene that regulates essential RNA splicing in the cochlea and vestibular system will lead to the discovery of novel molecular mechanisms, proteins, and protein isoforms that are required for hair cell differentiation and survival.
  6. Nuclear Function of Abl in DNA Damage Response
    Jean Y J Wang; Fiscal Year: 2012
    ..Alternative splicing has been shown to generate pro-death and anti-death protein isoforms from a single gene, underscoring the importance of splicing regulation in programmed cell death...
  7. Expression control in Drosophila splicing assembly factor RNP-4F
    JACK VAUGHN; Fiscal Year: 2010
    ..Specifically, we propose to: (1) Characterize the spatial and temporal expression of dADAR mRNA and protein isoforms during development; (2) Identify and evaluate the role of cis- and trans-acting factors in rnp-4f 5'-UTR ..
  8. Cellular Mechanisms of Lymphatic Muscle Contractility
    MICHAEL JOHN DAVIS; Fiscal Year: 2012
    ..Surprisingly, those vessels express contractile protein isoforms typically found only in striated muscle: troponin C (cTn-C), ?-striated tropomyosin (?-TMstr), and the fast, ..
  9. Role of LHX3 Protein Isoforms in Pituitary Development
    SIMON JAMES RHODES; Fiscal Year: 2012
    ..Further, clinical collaborations will continue to provide information that enhances our understanding of the basic mechanisms of pituitary development, thereby allowing the formulation of new research hypotheses. ..
  10. Role of Splicing Factors in Breast Cancer
    OLGA ANCZUKOW-CAMARDA; Fiscal Year: 2013
    ..Cancer cells often display aberrant profiles of alternative splicing, leading to the production of protein isoforms that can increase cell proliferation, migration, and apoptotic resistance...
  11. Changing tau Protein Levels and tau Protein Isoforms in Mouse Models of Dementia
    Timothy M Miller; Fiscal Year: 2012
    ..This novel therapeutic strategy, if successful, would be applicable to treating human dementias. ..
  12. Ubiquitin and regulation of prion induction by a short-lived protein
    Keith D Wilkinson; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Prions are infectious protein isoforms that cause fatal and incurable neurodegenerative diseases in mammals and transmit heritable traits in yeast...
  13. Macronutrient Regulation of Alternative Pre-mRNA Splicing
    Scot R Kimball; Fiscal Year: 2013
    ..high-fat diet results in an altered pattern of pre-mRNA splicing in skeletal muscle, leading to expression of protein isoforms that exhibit reduced force production and/or calcium sensitivity, as well as altered metabolism...
  14. Novel transgenic tools for analysis of 5HT2C receptor expression and function
    Ronald B Emeson; Fiscal Year: 2013
    ..In re- cent studies, we have demonstrated a disparity between 5HT2C mRNA and protein isoforms as genetically modified mice solely expressing the fully edited isoform of the 5HT2C receptor exhibit an ..
  15. MECHANISMS OF ENHANCER DEPENDENT SPLICE SITE ACTIVATION
    Klemens J Hertel; Fiscal Year: 2013
    ..pre-mRNA splicing is considered to be one of the most efficient and wide spread avenues to generate multiple protein isoforms from individual genes...
  16. Spliceosome Mechanism Dissected at the Single Molecule Level
    Nils G Walter; Fiscal Year: 2013
    ..humans, 94% of all pre-mRNAs undergo alternative splicing, which allows for the dynamic expression of various protein isoforms from a single gene through cell- and tissue-specific networks of regulated splicing events...
  17. RNA editing-mediated modulation of serotonin 2C receptor protein expression
    RANDI JO ULBRICHT; Fiscal Year: 2011
    ..receptor can be modified by up to five adenosine-to- inosine RNA editing events, generating as many as 24 protein isoforms that differ in their receptor:G-protein coupling efficacy and constitutive activity...
  18. Proteolytic silencing of cancer targets using engineered ubiquitin ligases
    Matthew P DeLisa; Fiscal Year: 2013
    ..such as glycosylation or phosphorylation, the technology has the potential for silencing of certain protein isoforms while sparing others...
  19. MOUSE MODELS OF DNA REPAIR - DEFECTIVE HUMAN DISEASES
    Errol Friedberg; Fiscal Year: 2011
    ..will clarify the in vivo functions of POLK and lead to further understanding of how POLK and it's protein isoforms interact with REV1L during polymerase switching will help define how this aspect of genome maintenance works ..
  20. Markers for HCV-related HCC: plasma profiling, targeted strategies and validation
    Laura Beretta; Fiscal Year: 2013
    ..They also offered new insights into protein isoforms that are potentially important in the development of HCC...
  21. The Biology and Biochemistry of ADAR RNA Editing Enzymes
    Brenda L Bass; Fiscal Year: 2013
    ..One function of ADARs is to target codons in mRNA to allow multiple protein isoforms from the information in a single gene...
  22. Isoform-Specific Regulation and Localization of the Coxsackie and Adenovirus Rece
    KATHERINE JULIE EXCOFFON; Fiscal Year: 2010
    ..Several protein isoforms have been described for CAR, including two transmembrane forms (CAREx7 and CAREx8)...
  23. Physiologic Roles of Activin and Myostatin Antagonists
    Alan L Schneyer; Fiscal Year: 2010
    ..Our preliminary data demonstrate that the, three FST protein isoforms and FSTL3 have different biochemical characteristics that contribute to distinct bioactivities and mechanisms ..
  24. Alternative splicing in the complex Drosophila dumpy gene
    Ross J MacIntyre; Fiscal Year: 2010
    ..We will explore the possibility that different ECM protein isoforms, generated by both cis and trans alternative splicing of mRNAs encoded by the complex dumpy gene, ..
  25. Epididymal PMCA4 Expression Functional Impact and Mechanism of Sperm Uptake
    PATRICIA ANASTASIA DELEON; Fiscal Year: 2013
    ..pattern and secretion of PMCA4 in all three regions of the murine epididymis by analyzing the mRNA and protein isoforms in tissues as well as in ELF and sperm, and 2) To determine if, and how, PMCA4/a is acquired in vitro on the ..
  26. Validation of Novel Peptide/Protein Markers for Diagnosis of Type 1 Diabetes
    Qibin Zhang; Fiscal Year: 2012
    ..disease controls of type 2 diabetes, celiac disease and inflammatory bowel disease;Aim 3, to identify the protein isoforms of key marker peptides having potential roles in pathogenesis of this disease;Aim 4, to validate the peptide ..
  27. Genomic and functional analysis of transcriptome changes in Huntington's Disease
    Yi Xing; Fiscal Year: 2013
    ..transcriptome alterations in HD may extend beyond up- and down-regulated genes to include changes in gene and protein isoforms. Assessing these events on a global scale for HD will aid efforts to unravel disease pathophysiology, and may ..
  28. Assays for Screening Histone Modifications in Cancer
    Michael A Freitas; Fiscal Year: 2013
    ..chromatography with high-mass accuracy mass spectrometry to profile histone proteins and characterize histone protein isoforms in primary malignant hematopoietic tumor cells...
  29. Informatics platform for mammalian gene regulation at isoform-level
    Ramana V Davuluri; Fiscal Year: 2013
    ..Recent evidence suggests that more than 50% of the human genes produce multiple protein isoforms, through alternative splicing and alternative usage of transcription initiation and/or termination...
  30. CARDIAC HYPERTROPHIC INTRACELLULAR SIGNALING PATHWAYS
    Jeffrey Robbins; Fiscal Year: 2013
    ..reprogramming occurs within the adult cardiomyocyte that results in the expression of genes encoding fetal protein isoforms. This fundamental reprogramming of gene expression occurs through activation of membrane bound receptors (..
  31. Comprehensive characterization of the Drosophila transcriptome
    Susan E Celniker; Fiscal Year: 2011
    ..Further, we plan to characterize and annotate the extent of splice variation used to generate protein isoforms and identify the sequences necessary for regulated alternative splicing utilizing in vivo splicing reporter ..
  32. Erythroid stage-specific transcriptome expression, dynamics, and regulation
    LIOR S PACHTER; Fiscal Year: 2013
    ..include greatly improved insights into regulation of biological processes in erythroid cells by alternative protein isoforms. Moreover, the RNA-Seq data itself may stimulate studies of the transcriptional and post-transcriptional ..
  33. Protein Markers to T1D Progression
    Qibin Zhang; Fiscal Year: 2013
    ..samples collected during the progression of T1D for a comprehensive identification of novel proteins and protein isoforms correlated to the progression of this disease...
  34. Assembly and stability of supramolecular PTB: exon complexes
    Kathleen B Hall; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Alternative splicing is the primary mechanism for generation of multiple protein isoforms. Regulation of alternative splicing often requires proteins specific to a cell type or developmental stage, ..
  35. Development of technologies for genome-wide identification of RNA branch points
    Christopher B Burge; Fiscal Year: 2013
    ..splicing of an average of 8-10 introns per mRNA, and most human genes produce multiple distinct mRNA and protein isoforms through alternative splicing...
  36. Regulation and Evolution of Alternative mRNA Isoform Expression in Mammals
    Christopher B Burge; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Most human genes produce multiple distinct mRNA and protein isoforms through alternative splicing (AS)...
  37. HORMONAL REGULATION OF BREAST CANCER
    JEFFREY MARK ROSEN; Fiscal Year: 2013
    ..4. To delineate the role of specific C/EBPss protein isoforms in both stem cell self-renewal and luminal/alveolar cell fate determination 5...
  38. Function of Sequence-Specific Regulators of RNA Splicing
    Christopher B Burge; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Most human genes produce multiple distinct mRNA and protein isoforms through alternative splicing that may have distinct or even antagonistic biological functions...
  39. Mechanisms of cell-type specific Dscam isoform expression
    Alex M Plocik; Fiscal Year: 2013
    ..Dscam can be alternatively splicing to conceivably generate over 38,000 different protein isoforms;without this complexity, neurons do not wire properly (3)...
  40. Mechanisms of signal-responsive alternative splicing in T-cell activation
    Nicole Martinez; Fiscal Year: 2013
    ..Finally, the functional distinction between the alternate protein isoforms of MKK7 that result from activation-induced alternative splicing will be investigated using standard ..
  41. Multidimensional proteomics platform
    Yehia Ibrahim; Fiscal Year: 2012
    ..using the "bottom-up" approach which is inefficient for distinguishing between biologically important protein isoforms and for identifications of post translational modifications of proteins...
  42. Multidimensional proteomics platform
    Yehia Ibrahim; Fiscal Year: 2011
    ..using the "bottom-up" approach which is inefficient for distinguishing between biologically important protein isoforms and for identifications of post translational modifications of proteins...
  43. Investigate the Role of Micro-RNA 155 in Myeloid Development during Inflammation
    RYAN O'CONNELL; Fiscal Year: 2013
    ..during inflammation, and does so by directly repressing SHIP1 and selecting specific C/EBP[unreadable] protein isoforms to be expressed...
  44. ALZHEIMERS DISEASE RESEARCH CENTER
    John Morris; Fiscal Year: 2013
    ..Changing tau protein levels and tau protein isoforms in mouse models of dementia;(Timothy Miller) 3. APOE metabolism in AD and controls;(Randall Bateman)...
  45. Computational and Experimental Analysis of RNA structures in mRNA polyadenylation
    BIN contact TIAN; Fiscal Year: 2010
    ..sites, leading to transcript variants containing distinct mRNA cis- regulatory elements and/or encoding protein isoforms. Alternative polyadenylation has been shown to be regulated in tissue- and condition-specific manners...
  46. Novel Tools for Detecting FGF8 for Developmental Biology Research
    Anne M Moon; Fiscal Year: 2012
    ..and range, receptor interactions, as well as tissue-specific production and processing of different FGF8 protein isoforms during mouse embryonic development in vivo...
  47. The Proteomic and Functional Profile of HIV Positive Saliva
    Linqi Zhang; Fiscal Year: 2011
    ..We also propose to characterize salivary protein isoforms, structural modifications, and concentrations of selected biomarkers altered in HIV-1 infection and to ..
  48. Tools for genome-wide profiling of mRNA translated in in-vivo dendrites
    Leon Reijmers; Fiscal Year: 2013
    ..the question which proteins can be synthesized in dendrites, but also provides insights into the specific protein isoforms that are synthesized...
  49. Novel Hybrid Bioanalytical System
    Mikhail Belov; Fiscal Year: 2013
    ..using the "bottom-up" approach which is inefficient for distinguishing between biologically important protein isoforms and for identifications of post translational modifications of proteins...
  50. Identification and Functional Characterization of Zebrafish microRNAs
    James Patton; Fiscal Year: 2009
    ..of gene expression is crucial to enable a relatively limited number of genes to encode a wide array of protein isoforms in a tissue- and developmental-specific pattern...
  51. Polyribosome targets mediating mRNA decay for cancer prediction and therapy
    Christopher Benz; Fiscal Year: 2012
    ..compartmentalization of this mRNA destruction machinery to the polyribosome facilitates a search for protein isoforms that regulate this switch, revealing novel cancer therapeutic targets...
  52. The role of MRL adaptor protein MIG-10 in neuronal migration in C. elegans
    Elizabeth F Ryder; Fiscal Year: 2010
    ..elegans. In Specific Aim 1, we propose to determine in which cell types each of the three MIG-10 protein isoforms is expressed, and also where their expression is required for function...
  53. Mass Spectrometry Imaging of Protein Gels
    Rachel R Ogorzalek Loo; Fiscal Year: 2013
    ..a high-throughput, integrated top-down mass spectrometry imaging platform to identify and characterize protein isoforms and expression profiles from complex biological samples and to elucidate effects of protein modifications on ..
  54. Mechanisms of DUX4 mediated FSHD pathology
    Peter L Jones; Fiscal Year: 2013
    ..In Specific Aim 3, we will identify gene networks that are differentially regulate by the DUX4 protein isoforms and determine if they are disrupted in DUX4-fl-expressing FSHD cells...
  55. Splicing factors as therapeutic targets for the treatment of ovarian cancer
    William T Beck; Fiscal Year: 2012
    ..Alternative splicing (AS), by allowing production of multiple protein isoforms from a single gene, plays a major role in expanding proteomic complexity in metazoans and adaptations to ..
  56. STRUCTURE/FUNCTION OF MYOSIN IN SKELETAL MUSCLE
    Gordon Lutz; Fiscal Year: 2001
    ..Recently, we have cloned four novel adult frog MHCs, identified the four corresponding protein isoforms and established their expression pattern in individual muscle cells...
  57. THE MECHANISM AND FUNCTION OF A TO I RNA EDITING
    Jinghua Yang; Fiscal Year: 2004
    Pre-mRNA editing is a recently discovered process that leads to the production of a variety of protein isoforms from a single gene...
  58. Biological role of modifications to C/EBPbeta-1 and -2
    Linda Sealy; Fiscal Year: 2007
    ..Alternative translation of the intronless C/EBPbeta gene produces three different protein isoforms. C/EBPbeta-1 and -2 are transactivators, whereas C/EBPbeta-3 lacks a transactivation domain and inhibits ..
  59. Physiological Basis of Vascular Contractility
    David Zawieja; Fiscal Year: 2006
    ..and force-velocity relationships of vascular SM; 3) expression of SM contractile and regulatory protein isoforms relative to myosin ATPase activity...
  60. C/EBPbeta Isoform Function & Regulation by Tyrosine Kinases
    Cynthia Zahnow; Fiscal Year: 2009
    ..Encoded by an intronless gene, C/EBPB is expressed as several distinct protein isoforms (LAP1, LAP2 and LIP) whose expression is tightly regulated by the differential use of a number of in-frame ..
  61. C/EDB BETA AND CHOP IN EPIDERMAL DIFFERENTIATION
    Edward Maytin; Fiscal Year: 2002
    ..that encode both activators and inhibitors of C/EBPbeta and CHOP (including antisense RNA, and inhibitory protein isoforms of C/EBPs) will be studied in a calcium-dependent differentiation model in vitro...
  62. Role of PPAR-gamma Isoforms in Regulation of Macrophage apoE & LPL Expression
    Jheem Medh; Fiscal Year: 2006
    ..Together, the 7 transcripts encode for 3 different PPAR-g protein isoforms. PPAR-g are multifunctional protein transcription factors responsible for the regulation of many different ..
  63. Molecular genetic analysis of UNC-82 kinase function in C. elegans muscle
    Pamela E Hoppe; Fiscal Year: 2010
    ..Interestingly, through alternative splicing, the single C. elegans gene unc-82 also produces protein isoforms that differ in the presence or absence of the Akt regulatory phosphorylation site...
  64. MECHANISM OF MIS-SPLICING IN MYOTONIC DYSTROPHY 1
    MUGE KUYUMCU MARTINEZ; Fiscal Year: 2007
    ..pathogenesis of DM1 involves misregulation of alternative splicing resulting in expression of inappropriate protein isoforms causing specific symptoms...
  65. THE ROLE OF ZINC FINGER GENES IN HEMATOPOIESIS
    Sinisa Dovat; Fiscal Year: 2003
    ..Ikaros encodes a zinc finger protein whose expression is restricted to hematopoietic cells. Ikaros protein isoforms are expressed in a constitutively phosphorylated form, most abundantly in lymphocytes...
  66. Targeting HMGA1 in Pancreatic Tumor Progression
    Linda M S Resar; Fiscal Year: 2010
    ..Our focus is the HMGA1 oncogene, which encodes the HMGA1a and HMGA1b protein isoforms. These chromatin binding proteins function in regulating gene expression...
  67. Myofilament Protein Isoforms in Neuromuscular Reflex
    Jian Ping Jin; Fiscal Year: 2005
    ..Based on our previous studies, we plan to investigate the role of myofilament protein isoforms in neuromuscular reflex...
  68. REGULATION OF ALTERNATIVE RNA SPLICING IN A-TROPOMYOSIN
    David Wieczorek; Fiscal Year: 1992
    ..post-transcriptional processing is important in the regulated expression of structurally distinct protein isoforms, essential to eukaryotic development and cell differentiation...