protein binding


Summary: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.

Top Publications

  1. pmc AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility
    Garrett M Morris
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Comput Chem 30:2785-91. 2009
  2. ncbi Crystal structure of the nucleosome core particle at 2.8 A resolution
    K Luger
    Institut fur Molekularbiologie und Biophysik, Zurich, Switzerland
    Nature 389:251-60. 1997
  3. pmc p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death
    Geir Bjørkøy
    Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
    J Cell Biol 171:603-14. 2005
  4. pmc JASPAR 2010: the greatly expanded open-access database of transcription factor binding profiles
    Elodie Portales-Casamar
    Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, BC V5Z 4H4, Canada
    Nucleic Acids Res 38:D105-10. 2010
  5. ncbi p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy
    Serhiy Pankiv
    Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
    J Biol Chem 282:24131-45. 2007
  6. pmc Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
    Ewan Birney
    Nature 447:799-816. 2007
  7. ncbi MatInspector and beyond: promoter analysis based on transcription factor binding sites
    K Cartharius
    Genomatix Software GmbH Landsberger Strasse 6, 80339 München, Germany
    Bioinformatics 21:2933-42. 2005
  8. pmc Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists
    Beili Wu
    Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 330:1066-71. 2010
  9. pmc Crystal structure of the β2 adrenergic receptor-Gs protein complex
    Søren G F Rasmussen
    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA
    Nature 477:549-55. 2011
  10. ncbi The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression
    A Cano
    Instituto de Investigaciones Biomedicas, Arturo Duperier 4, 28029 Madrid, Spain
    Nat Cell Biol 2:76-83. 2000

Detail Information

Publications320 found, 100 shown here

  1. pmc AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility
    Garrett M Morris
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Comput Chem 30:2785-91. 2009
    ..We also report its utility in analysis of covalently bound ligands, using both a grid-based docking method and a modification of the flexible sidechain technique...
  2. ncbi Crystal structure of the nucleosome core particle at 2.8 A resolution
    K Luger
    Institut fur Molekularbiologie und Biophysik, Zurich, Switzerland
    Nature 389:251-60. 1997
    ..The lack of uniformity between multiple histone/DNA-binding sites causes the DNA to deviate from ideal superhelix geometry...
  3. pmc p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death
    Geir Bjørkøy
    Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
    J Cell Biol 171:603-14. 2005
    ..We suggest that p62 may, via LC3, be involved in linking polyubiquitinated protein aggregates to the autophagy machinery...
  4. pmc JASPAR 2010: the greatly expanded open-access database of transcription factor binding profiles
    Elodie Portales-Casamar
    Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, 950 West 28th Avenue, Vancouver, BC V5Z 4H4, Canada
    Nucleic Acids Res 38:D105-10. 2010
    ..Additionally, three new special collections provide matrix profile data produced by recent alternative high-throughput approaches...
  5. ncbi p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy
    Serhiy Pankiv
    Biochemistry Department, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway
    J Biol Chem 282:24131-45. 2007
    ..In fact, p62 bodies and these structures are indistinguishable. Taken together, our results clearly suggest that p62 is required both for the formation and the degradation of polyubiquitin-containing bodies by autophagy...
  6. pmc Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
    Ewan Birney
    Nature 447:799-816. 2007
    ..Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function...
  7. ncbi MatInspector and beyond: promoter analysis based on transcription factor binding sites
    K Cartharius
    Genomatix Software GmbH Landsberger Strasse 6, 80339 München, Germany
    Bioinformatics 21:2933-42. 2005
    ..The next steps in promoter analysis can be tackled only with reliable predictions, e.g. finding phylogenetically conserved patterns or identifying higher order combinations of sites in promoters of co-regulated genes...
  8. pmc Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists
    Beili Wu
    Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 330:1066-71. 2010
    ..These structures provide new clues about the interactions between CXCR4 and its natural ligand CXCL12, and with the HIV-1 glycoprotein gp120...
  9. pmc Crystal structure of the β2 adrenergic receptor-Gs protein complex
    Søren G F Rasmussen
    Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA
    Nature 477:549-55. 2011
    ..The most surprising observation is a major displacement of the α-helical domain of Gαs relative to the Ras-like GTPase domain. This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR...
  10. ncbi The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression
    A Cano
    Instituto de Investigaciones Biomedicas, Arturo Duperier 4, 28029 Madrid, Spain
    Nat Cell Biol 2:76-83. 2000
    ..Snail may thus be considered as a marker for malignancy, opening up new avenues for the design of specific anti-invasive drugs...
  11. ncbi LigPlot+: multiple ligand-protein interaction diagrams for drug discovery
    Roman A Laskowski
    European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, United Kingdom
    J Chem Inf Model 51:2778-86. 2011
  12. pmc Selective inhibition of BET bromodomains
    Panagis Filippakopoulos
    Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK
    Nature 468:1067-73. 2010
    ..These data establish proof-of-concept for targeting protein-protein interactions of epigenetic 'readers', and provide a versatile chemical scaffold for the development of chemical probes more broadly throughout the bromodomain family...
  13. pmc MEME-ChIP: motif analysis of large DNA datasets
    Philip Machanick
    Institute for Molecular Bioscience, The University of Queensland, Brisbane 4072, Queensland, Australia
    Bioinformatics 27:1696-7. 2011
    ..While there are many existing tools for discovering TF binding site motifs in such datasets, most web-based tools cannot directly process such large datasets...
  14. ncbi The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
    P H Maxwell
    Wellcome Trust Centre for Human Genetics, Oxford, UK
    Nature 399:271-5. 1999
    ..Thus, constitutive HIF-1 activation may underlie the angiogenic phenotype of VHL-associated tumours. The pVHL/HIF-1 interaction provides a new focus for understanding cellular oxygen sensing...
  15. pmc Diversity and complexity in DNA recognition by transcription factors
    Gwenael Badis
    Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada
    Science 324:1720-3. 2009
    ..This complexity in DNA recognition may be important in gene regulation and in the evolution of transcriptional regulatory networks...
  16. ncbi Breaking the code of DNA binding specificity of TAL-type III effectors
    Jens Boch
    Department of Genetics, Institute of Biology, Martin Luther University Halle Wittenberg, Weinbergweg 10, D 06099 Halle Saale Germany
    Science 326:1509-12. 2009
    ..Our study describes the functionality of a distinct type of DNA binding domain and allows the design of DNA binding domains for biotechnology...
  17. pmc Core transcriptional regulatory circuitry in human embryonic stem cells
    Laurie A Boyer
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Cell 122:947-56. 2005
    ..These results provide new insights into the transcriptional regulation of stem cells and reveal how OCT4, SOX2, and NANOG contribute to pluripotency and self-renewal...
  18. ncbi Shelterin: the protein complex that shapes and safeguards human telomeres
    Titia de Lange
    The Rockefeller University, New York, New York 10021, USA
    Genes Dev 19:2100-10. 2005
    ..Six shelterin subunits: TRF1, TRF2, TIN2, Rap1, TPP1, and POT1...
  19. pmc Mediator and cohesin connect gene expression and chromatin architecture
    Michael H Kagey
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 467:430-5. 2010
    ..Mediator and cohesin co-occupy different promoters in different cells, thus generating cell-type-specific DNA loops linked to the gene expression program of each cell...
  20. pmc An oestrogen-receptor-alpha-bound human chromatin interactome
    Melissa J Fullwood
    Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672
    Nature 462:58-64. 2009
    ..We propose that chromatin interactions constitute a primary mechanism for regulating transcription in mammalian genomes...
  21. ncbi DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
    Christopher J Bakkenist
    Department of Hematology Oncology, St Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, Tennessee 38105, USA
    Nature 421:499-506. 2003
  22. ncbi Mdm2 promotes the rapid degradation of p53
    Y Haupt
    Lautenberg Center for General and Tumor Immunology, The Hebrew University Haddassah Medical School, Jerusalem, Israel
    Nature 387:296-9. 1997
    ..During recovery from DNA damage, maximal Mdm2 induction coincides with rapid p53 loss. We propose that the Mdm2-promoted degradation of p53 provides a new mechanism to ensure effective termination of the p53 signal...
  23. ncbi Molecular chaperones in the cytosol: from nascent chain to folded protein
    F Ulrich Hartl
    Department of Cellular Biochemistry, Max Planck Institut fur Biochemie, Am Klopferspitz 18a, D 82152 Martinsried, Germany
    Science 295:1852-8. 2002
    ..Understanding how the thousands of different proteins synthesized in a cell use this chaperone machinery has profound implications for biotechnology and medicine...
  24. ncbi The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex
    Beom Seok Park
    Department of Chemistry, KAIST, Daejeon, 305 701, Korea
    Nature 458:1191-5. 2009
    ..The TLR4-MD-2-LPS structure illustrates the remarkable versatility of the ligand recognition mechanisms employed by the TLR family, which is essential for defence against diverse microbial infection...
  25. pmc The KEGG resource for deciphering the genome
    Minoru Kanehisa
    Bioinformatics Center, Institute for Chemical Research, Kyoto University, Uji, Kyoto 611 0011, Japan
    Nucleic Acids Res 32:D277-80. 2004
    ..New efforts are being made to abstract knowledge, both computationally and manually, about ortholog clusters in the KO (KEGG Orthology) database, and to collect and analyze carbohydrate structures in the GLYCAN database...
  26. ncbi hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase
    H Vaziri
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Cell 107:149-59. 2001
    ..In contrast, expression of a catalytically inactive hSir2 protein potentiates p53-dependent apoptosis and radiosensitivity. We propose that hSir2 is involved in the regulation of p53 function via deacetylation...
  27. pmc The role of DNA shape in protein-DNA recognition
    Remo Rohs
    Howard Hughes Medical Institute, Center for Computational Biology and Bioinformatics, Department of Biochemistry and Molecular Biophysics, Columbia University, 1130 Saint Nicholas Avenue, New York, New York 10032, USA
    Nature 461:1248-53. 2009
  28. ncbi Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes
    Lee Zou
    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Science 300:1542-8. 2003
    ..Our data suggest that RPA-coated ssDNA is the critical structure at sites of DNA damage that recruits the ATR-ATRIP complex and facilitates its recognition of substrates for phosphorylation and the initiation of checkpoint signaling...
  29. ncbi Chromatin accessibility pre-determines glucocorticoid receptor binding patterns
    Sam John
    Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
    Nat Genet 43:264-8. 2011
    ..The results define a framework for understanding regulatory factor-genome interactions and provide a molecular basis for the tissue selectivity of steroid pharmaceuticals and other agents that intersect the living genome...
  30. ncbi HDAC6 is a microtubule-associated deacetylase
    Charlotte Hubbert
    Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina 27710, USA
    Nature 417:455-8. 2002
    ..Our results show that HDAC6 is the tubulin deacetylase, and provide evidence that reversible acetylation regulates important biological processes beyond histone metabolism and gene transcription...
  31. ncbi Global analysis of protein localization in budding yeast
    Won Ki Huh
    Howard Hughes Medical Institute, University of California San Francisco, Department of Biochemistry and Biophysics, 600 16th Street, San Francisco, California 94143 2240, USA
    Nature 425:686-91. 2003
  32. pmc Membrane fusion: grappling with SNARE and SM proteins
    Thomas C Sudhof
    Department of Cellular and Molecular Physiology, Stanford University, Palo Alto, CA 94304, USA
    Science 323:474-7. 2009
  33. ncbi Genome-wide mapping of in vivo protein-DNA interactions
    David S Johnson
    Department of Genetics, Stanford University School of Medicine, Stanford, CA, 94305 5120, USA
    Science 316:1497-502. 2007
    ..96] and statistical confidence (P <10(-4)), properties that were important for inferring new candidate interactions. These include key transcription factors in the gene network that regulates pancreatic islet cell development...
  34. pmc Network organization of the human autophagy system
    Christian Behrends
    Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 466:68-76. 2010
    ..These studies provide a global view of the mammalian autophagy interaction landscape and a resource for mechanistic analysis of this critical protein homeostasis pathway...
  35. ncbi Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus
    Etienne Meylan
    Department of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Nature 437:1167-72. 2005
    ..Cardif thus functions as an adaptor, linking the cytoplasmic dsRNA receptor RIG-I to the initiation of antiviral programmes...
  36. ncbi The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases
    J W Harper
    Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030
    Cell 75:805-16. 1993
    ..Cotransfection experiments indicate that CIP1 and SV40 T antigen function in a mutually antagonistic manner to control cell cycle progression...
  37. pmc Abscisic acid inhibits type 2C protein phosphatases via the PYR/PYL family of START proteins
    Sang Youl Park
    Department of Botany and Plant Sciences, University of California at Riverside, Riverside, CA 92521, USA
    Science 324:1068-71. 2009
    ..Our results illustrate the power of the chemical genetic approach for sidestepping genetic redundancy...
  38. ncbi Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis
    Jesper V Olsen
    Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Am Klopferspitz 18, D 82152 Martinsried near Munich, Germany
    Sci Signal 3:ra3. 2010
    ..In particular, nuclear proteins and proteins involved in regulating metabolic processes have high phosphorylation site occupancy in mitosis. This suggests that these proteins may be inactivated by phosphorylation in mitotic cells...
  39. pmc The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1
    Yasemin Sancak
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology MIT, Nine Cambridge Center, Cambridge, MA 02142, USA
    Science 320:1496-501. 2008
    ..The Rag proteins do not directly stimulate the kinase activity of mTORC1, but, like amino acids, promote the intracellular localization of mTOR to a compartment that also contains its activator Rheb...
  40. pmc TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing
    Thimmaiah P Chendrimada
    The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA
    Nature 436:740-4. 2005
    ..These results support a role of the Dicer-TRBP complex not only in miRNA processing but also as a platform for RISC assembly...
  41. ncbi Reaching for high-hanging fruit in drug discovery at protein-protein interfaces
    James A Wells
    Department of Pharmaceutical Chemistry, University of California at San Francisco, 1700 4th Street 503A, San Francisco, California 94156, USA
    Nature 450:1001-9. 2007
    ..Some of these small molecules are now making their way through clinical trials, so this high-hanging fruit might not be far out of reach...
  42. pmc The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist
    Veli Pekka Jaakola
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037 USA
    Science 322:1211-7. 2008
  43. ncbi GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors
    Kent L Rossman
    Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Nat Rev Mol Cell Biol 6:167-80. 2005
    ..The failure to do so can have significant consequences and is reflected in the aberrant function of Dbl-family GEFs in some human diseases...
  44. ncbi Functional interaction of beta-catenin with the transcription factor LEF-1
    J Behrens
    Max Delbruck Centre for Molecular Medicine, Berlin, Germany
    Nature 382:638-42. 1996
    ..Thus beta-catenin regulates gene expression by direct interaction with transcription factors such as LEF-1, providing a molecular mechanism for the transmission of signals, from cell-adhesion components or wnt protein to the nucleus...
  45. pmc High-resolution DNA-binding specificity analysis of yeast transcription factors
    Cong Zhu
    Division of Genetics, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Genome Res 19:556-66. 2009
    ..These approaches could be adapted to identify TFs and cis regulatory elements in higher eukaryotes...
  46. pmc AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC
    Veit Hornung
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Nature 458:514-8. 2009
    ..Collectively, these observations identify AIM2 as a new receptor for cytoplasmic DNA, which forms an inflammasome with the ligand and ASC to activate caspase-1...
  47. pmc The crystal structure of TAL effector PthXo1 bound to its DNA target
    Amanda Nga Sze Mak
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, A3 025 Seattle, WA 98019, USA
    Science 335:716-9. 2012
    ..Two degenerate amino-terminal repeats also interact with the DNA. Containing several RVDs and noncanonical associations, the structure illustrates the basis of TAL effector-DNA recognition...
  48. ncbi Crystal structure of the eukaryotic ribosome
    Adam Ben-Shem
    IGBMC Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 rue Laurent Fries, BP10142, Illkirch F 67400, France
    Science 330:1203-9. 2010
    ..We describe the conformational changes in both ribosomal subunits that are involved in ratcheting and their implications in coordination between the two associated subunits and in mRNA and tRNA translocation...
  49. ncbi The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells
    E Batlle
    Unitat de Biologia Cel lular i Molecular, Institut Municipal d Investigacio Medica, Universitat Pompeu Fabra, Dr Aiguader 80, 08003 Barcelona, Spain
    Nat Cell Biol 2:84-9. 2000
    ..Inhibition of Snail function in epithelial cancer cell lines lacking E-cadherin protein restores the expression of the E-cadherin gene...
  50. pmc Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control
    Bin Zhao
    Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA
    Genes Dev 21:2747-61. 2007
    ..Our observations demonstrate that YAP plays a key role in the Hippo pathway to control cell proliferation in response to cell contact...
  51. pmc Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding
    Dominic Schmidt
    Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK
    Science 328:1036-40. 2010
    ..Our results reveal large interspecies differences in transcriptional regulation and provide insight into regulatory evolution...
  52. pmc Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding
    Stephen G Aller
    Department of Molecular Biology, Scripps Research Institute, 10550 North Torrey Pines Road, CB105, La Jolla, CA 92037, USA
    Science 323:1718-22. 2009
    ..The inward-facing conformation represents an initial stage of the transport cycle that is competent for drug binding...
  53. pmc The HSP70 chaperone machinery: J proteins as drivers of functional specificity
    Harm H Kampinga
    Department of Cell Biology, University of Groningen, University Medical Center, 713 AV Groningen, The Netherlands
    Nat Rev Mol Cell Biol 11:579-92. 2010
    ..Some target HSP70 activity to clients at precise locations in cells and others bind client proteins directly, thereby delivering specific clients to HSP70 and directly determining their fate...
  54. pmc Design and analysis of ChIP-seq experiments for DNA-binding proteins
    Peter V Kharchenko
    Center for Biomedical Informatics, Harvard Medical School, 10 Shattuck St, Boston, Massachusetts 02115, USA
    Nat Biotechnol 26:1351-9. 2008
    ..We also analyze the relationship between the depth of sequencing and characteristics of the detected binding positions, and provide a method for estimating the sequencing depth necessary for a desired coverage of protein binding sites.
  55. ncbi Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade
    P Li
    Howard Hughes Medical Institute, and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 75235, USA
    Cell 91:479-89. 1997
  56. pmc Host cell factors in HIV replication: meta-analysis of genome-wide studies
    Frederic D Bushman
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    PLoS Pathog 5:e1000437. 2009
  57. ncbi Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control
    Robbie Loewith
    Division of Biochemistry, Biozentrum, University of Basel, Klingelbergstrasse 70, CH 4056 Basel, Switzerland
    Mol Cell 10:457-68. 2002
    ..Thus, the distinct TOR complexes account for the diversity, specificity, and selective rapamycin inhibition of TOR signaling. TORC1 and possibly TORC2 are conserved from yeast to man...
  58. pmc LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1
    Jose M Lizcano
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee, UK
    EMBO J 23:833-43. 2004
    ..Between them, these kinases may mediate the physiological effects of LKB1, including its tumour suppressor function...
  59. pmc Regulation of alternative splicing by histone modifications
    Reini F Luco
    National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Science 327:996-1000. 2010
    ..Histone marks affect splicing outcome by influencing the recruitment of splicing regulators via a chromatin-binding protein. These results outline an adaptor system for the reading of histone marks by the pre-mRNA splicing machinery...
  60. ncbi A quantitative analysis of kinase inhibitor selectivity
    Mazen W Karaman
    Ambit Biosciences, 4215 Sorrento Valley Blvd, San Diego, California 92121, USA
    Nat Biotechnol 26:127-32. 2008
    ..We further investigate the impact of panel size and find that small assay panels do not provide a robust measure of selectivity...
  61. pmc An empirical framework for binary interactome mapping
    Kavitha Venkatesan
    Center for Cancer Systems Biology and Department of Cancer Biology, Dana Farber Cancer Institute, 1 Jimmy Fund Way, Boston, MA 02115, USA
    Nat Methods 6:83-90. 2009
  62. ncbi Converging concepts of protein folding in vitro and in vivo
    F Ulrich Hartl
    Max Planck Institute of Biochemistry, Department of Cellular Biochemistry, Martinsried, Germany
    Nat Struct Mol Biol 16:574-81. 2009
  63. pmc Combinatorial patterns of histone acetylations and methylations in the human genome
    Zhibin Wang
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, US National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Genet 40:897-903. 2008
    ..Our data suggest that these histone modifications may act cooperatively to prepare chromatin for transcriptional activation...
  64. pmc Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia
    Mark A Dawson
    Department of Haematology, Cambridge Institute for Medical Research and Addenbrookes Hospital, University of Cambridge, Cambridge CB2 0XY, UK
    Nature 478:529-33. 2011
    ..These findings establish the displacement of BET proteins from chromatin as a promising epigenetic therapy for these aggressive leukaemias...
  65. pmc Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers
    Juha Lauren
    Cellular Neuroscience, Neurodegeneration and Repair Program, Yale University School of Medicine, New Haven, Connecticut 06536, USA
    Nature 457:1128-32. 2009
    ..Thus, PrP(C) is a mediator of amyloid-beta-oligomer-induced synaptic dysfunction, and PrP(C)-specific pharmaceuticals may have therapeutic potential for Alzheimer's disease...
  66. ncbi Negative control of p53 by Sir2alpha promotes cell survival under stress
    J Luo
    Institute of Cancer Genetics and Department of Pathology, College of Physicians and Surgeons, Columbia University, 1150 St Nicholas Avenue, New York, NY 10032, USA
    Cell 107:137-48. 2001
    ..These results have significant implications regarding an important role for Sir2alpha in modulating the sensitivity of cells in p53-dependent apoptotic response and the possible effect in cancer therapy...
  67. ncbi Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response
    A Bertolotti
    Skirball Institute of Biomolecular Medicine, Departments of Medicine and Cell Biology and the Kaplan Cancer Center, New York University School of Medicine, New York, New York 10016, USA
    Nat Cell Biol 2:326-32. 2000
    ..These findings are consistent with a model in which BiP represses signalling through PERK and IRE1 and protein misfolding relieves this repression by effecting the release of BiP from the PERK and IRE1 lumenal domains...
  68. ncbi The F-box protein TIR1 is an auxin receptor
    Nihal Dharmasiri
    Department of Biology, Indiana University, Bloomington, Indiana 47405, USA
    Nature 435:441-5. 2005
    ..Finally, TIR1 synthesized in insect cells binds Aux/IAA proteins in an auxin-dependent manner. Together, these results indicate that TIR1 is an auxin receptor that mediates Aux/IAA degradation and auxin-regulated transcription...
  69. pmc APP binds DR6 to trigger axon pruning and neuron death via distinct caspases
    Anatoly Nikolaev
    Division of Research, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nature 457:981-9. 2009
    ..Our results indicate that APP and DR6 are components of a neuronal self-destruction pathway, and suggest that an extracellular fragment of APP, acting via DR6 and caspase 6, contributes to Alzheimer's disease...
  70. pmc Structure of the human histamine H1 receptor complex with doxepin
    Tatsuro Shimamura
    Human Receptor Crystallography Project, ERATO, Japan Science and Technology Agency, Kyoto 606 8501, Japan
    Nature 475:65-70. 2011
    ..Our study sheds light on the molecular basis of H(1)R antagonist specificity against H(1)R...
  71. pmc Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization
    J A Diehl
    Howard Hughes Medical Institute, St Jude Children s Research Hospital, Memphis, Tennessee 38105 USA
    Genes Dev 12:3499-511. 1998
    ..Therefore, phosphorylation and proteolytic turnover of cyclin D1 and its subcellular localization during the cell division cycle are linked through the action of GSK-3beta...
  72. ncbi Transposable elements have rewired the core regulatory network of human embryonic stem cells
    Galih Kunarso
    Computational and Mathematical Biology, Genome Institute of Singapore, Singapore, Singapore
    Nat Genet 42:631-4. 2010
    ..These data indicate that species-specific transposable elements have substantially altered the transcriptional circuitry of pluripotent stem cells...
  73. ncbi Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex
    X Nan
    Institute of Cell and Molecular Biology, University of Edinburgh, UK
    Nature 393:386-9. 1998
    ..The data suggest that two global mechanisms of gene regulation, DNA methylation and histone deacetylation, can be linked by MeCP2...
  74. ncbi Specificity and stability in topology of protein networks
    Sergei Maslov
    Department of Physics, Brookhaven National Laboratory, Upton, NY 11973, USA
    Science 296:910-3. 2002
    ..This effect decreases the likelihood of cross talk between different functional modules of the cell and increases the overall robustness of a network by localizing effects of deleterious perturbations...
  75. pmc Structural basis for RNA 3'-end recognition by Hfq
    Evelyn Sauer
    Department of Biochemistry, Max Planck Institute for Developmental Biology, 72076 Tubingen, Germany
    Proc Natl Acad Sci U S A 108:13065-70. 2011
    ..The capacity of Hfq to occupy and sequester the RNA 3' end has important implications for the mechanisms by which Hfq is thought to affect sRNA stability, turnover, and regulation...
  76. pmc Induced fit, conformational selection and independent dynamic segments: an extended view of binding events
    Peter Csermely
    Department of Medical Chemistry, Semmelweis University, PO Box 260, H 1444 Budapest 8, Hungary
    Trends Biochem Sci 35:539-46. 2010
    ..Additionally, we highlight the dynamic complexity of binding scenarios as they relate to events such as aggregation and signalling, and the crowded cellular environment...
  77. ncbi Refined structure of alpha beta-tubulin at 3.5 A resolution
    J Lowe
    MRC Laboratory of Molecular Biology, Cambridge, UK
    J Mol Biol 313:1045-57. 2001
    ..In light of the new model we discuss details of the tubulin structure such as nucleotide and taxol binding sites, lateral contacts in zinc-sheets, and the significance of the location of highly conserved residues...
  78. ncbi Drosophila enhancer of Zeste/ESC complexes have a histone H3 methyltransferase activity that marks chromosomal Polycomb sites
    Birgit Czermin
    Adolf Butenandt Institut, University of Munich, Schillerstrasse 44, 80336 Munich, Germany
    Cell 111:185-96. 2002
    ..Histone H3 methylated in vitro by the E(Z)/ESC complex binds specifically to Polycomb protein...
  79. ncbi Genome-wide profiles of STAT1 DNA association using chromatin immunoprecipitation and massively parallel sequencing
    Gordon Robertson
    British Columbia Cancer Agency Genome Sciences Centre, 675 West 10th Avenue, Vancouver, British Columbia V5Z 4S6, Canada
    Nat Methods 4:651-7. 2007
    ..ChIP-seq targets were enriched in sequences similar to known STAT1 binding motifs. Comparisons with two ChIP-PCR data sets suggested that ChIP-seq sensitivity was between 70% and 92% and specificity was at least 95%...
  80. ncbi p53 has a direct apoptogenic role at the mitochondria
    Motohiro Mihara
    Department of Pathology, Stony Brook University, Stony Brook, NY 11794, USA
    Mol Cell 11:577-90. 2003
    ..This opens the possibility that mutations might represent "double-hits" by abrogating the transcriptional and mitochondrial apoptotic activity of p53...
  81. pmc Robust hepatitis C virus infection in vitro
    Jin Zhong
    Departments of Molecular and Experimental Medicine and Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 102:9294-9. 2005
    ..This system provides a powerful tool for the analysis of host-virus interactions that should facilitate the discovery of antiviral drugs and vaccines for this important human pathogen...
  82. ncbi The tail of integrins, talin, and kindlins
    Markus Moser
    Max Planck Institute of Biochemistry, 82152 Martinsried, Germany
    Science 324:895-9. 2009
    ..This review focuses on the mechanisms whereby two key proteins, talin and the kindlins, regulate integrin activation by binding the tails of integrin-beta subunits...
  83. pmc Diverse RNA-binding proteins interact with functionally related sets of RNAs, suggesting an extensive regulatory system
    Daniel J Hogan
    Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America
    PLoS Biol 6:e255. 2008
    ..These results strongly suggest that combinatorial binding of RBPs to specific recognition elements in mRNAs is a pervasive mechanism for multi-dimensional regulation of their post-transcriptional fate...
  84. pmc Structure of a V3-containing HIV-1 gp120 core
    Chih Chin Huang
    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA
    Science 310:1025-8. 2005
    ..The extended nature and antibody accessibility of V3 explain its immunodominance. Together, the results provide a structural rationale for the role of V3 in HIV entry and neutralization...
  85. ncbi The Microprocessor complex mediates the genesis of microRNAs
    Richard I Gregory
    The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA
    Nature 432:235-40. 2004
    ..In vivo knock-down and in vitro reconstitution studies revealed that both components of this smaller complex, termed Microprocessor, are necessary and sufficient in mediating the genesis of miRNAs from the primary miRNA transcript...
  86. pmc Preferential associations between co-regulated genes reveal a transcriptional interactome in erythroid cells
    Stefan Schoenfelder
    Laboratory of Chromatin and Gene Expression, Babraham Research Campus, Cambridge, UK
    Nat Genet 42:53-61. 2010
    ..Our results establish a new gene expression paradigm, implying that active co-regulated genes and their regulatory factors cooperate to create specialized nuclear hot spots optimized for efficient and coordinated transcriptional control...
  87. ncbi Mass spectrometry-based proteomics
    Ruedi Aebersold
    Institute for Systems Biology, 1441 North 34th Street, Seattle, Washington 98103 8904, USA
    Nature 422:198-207. 2003
    ..The ability of mass spectrometry to identify and, increasingly, to precisely quantify thousands of proteins from complex samples can be expected to impact broadly on biology and medicine...
  88. ncbi Ubiquitin-binding domains - from structures to functions
    Ivan Dikic
    Institute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University Frankfurt, Germany
    Nat Rev Mol Cell Biol 10:659-71. 2009
    ..These new structure-based insights provide strategies for controlling cellular processes by targeting ubiquitin-UBD interfaces...
  89. pmc Purified human BRCA2 stimulates RAD51-mediated recombination
    Ryan B Jensen
    Department of Microbiology, University of California, Davis, California 95616, USA
    Nature 467:678-83. 2010
  90. pmc Recognition of trimethylated histone H3 lysine 4 facilitates the recruitment of transcription postinitiation factors and pre-mRNA splicing
    Robert J Sims
    Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA
    Mol Cell 28:665-76. 2007
    ..These findings suggest that methylated H3K4 serves to facilitate the competency of pre-mRNA maturation through the bridging of spliceosomal components to H3K4me3 via CHD1...
  91. pmc Developmental roles of 21 Drosophila transcription factors are determined by quantitative differences in binding to an overlapping set of thousands of genomic regions
    Stewart MacArthur
    Genomics Division, Lawrence Berkeley National Laboratory, Cyclotron Road MS 84 181, Berkeley, CA 94720, USA
    Genome Biol 10:R80. 2009
  92. ncbi SIR2 and SIR4 interactions differ in core and extended telomeric heterochromatin in yeast
    S Strahl-Bolsinger
    Department of Biological Chemistry, University of California, Los Angeles 90095, USA
    Genes Dev 11:83-93. 1997
    ..RAP1 binding at the core region is unaffected by SIR3 overproduction and RAP1 shows no evidence of spreading. Thus, we propose that the structure of core telomeric heterochromatin differs from that extended by SIR3...
  93. pmc Systematic analysis of human protein complexes identifies chromosome segregation proteins
    James R A Hutchins
    Research Institute of Molecular Pathology IMP, Dr Bohr Gasse 7, A 1030 Vienna, Austria
    Science 328:593-9. 2010
    ..The approaches we describe here are generally applicable to high-throughput follow-up analyses of phenotypic screens in mammalian cells...
  94. pmc Genome-wide analysis of ETS-family DNA-binding in vitro and in vivo
    Gong Hong Wei
    Public Health Genomics Unit, National Institute for Health and Welfare THL and Genome Scale Biology Program, Institute of Biomedicine and High Throughput Center, University of Helsinki, Biomedicum, Helsinki, Finland
    EMBO J 29:2147-60. 2010
    ..The results indicate that even relatively small differences in in vitro binding specificity of a TF contribute to site selectivity in vivo...
  95. ncbi A semiempirical free energy force field with charge-based desolvation
    Ruth Huey
    Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92102, USA
    J Comput Chem 28:1145-52. 2007
    ..The force field shows improvement in redocking simulations over the previous AutoDock3 force field...
  96. ncbi Global, in vivo, and site-specific phosphorylation dynamics in signaling networks
    Jesper V Olsen
    Center for Experimental Bioinformatics, Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK 5230 Odense, Denmark
    Cell 127:635-48. 2006
    ..The dynamic phosphoproteome provides a missing link in a global, integrative view of cellular regulation...
  97. pmc Benchmarking sets for molecular docking
    Niu Huang
    Department of Pharmaceutical Chemistry, University of California San Francisco, QB3 Building, 1700 4th Street, Box 2550, San Francisco, California 94143 2550, USA
    J Med Chem 49:6789-801. 2006
    ..DUD is freely available online as a benchmarking set for docking at
  98. pmc Molecular architecture of native HIV-1 gp120 trimers
    Jun Liu
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Nature 455:109-13. 2008
    ..Our findings elucidate the structure and conformational changes of trimeric HIV-1 gp120 relevant to antibody neutralization and attachment to target cells...
  99. ncbi MeCP2 binding to DNA depends upon hydration at methyl-CpG
    Kok Lian Ho
    School of Biological Sciences, University of Edinburgh, King s Buildings, Mayfield Road, Edinburgh EH9 3JR, UK
    Mol Cell 29:525-31. 2008
    ..The MeCP2-DNA complex also identifies a unique structural role for T158, the residue most commonly mutated in Rett syndrome...
  100. pmc A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation
    Xin Zeng
    Neurobiology Program, Children s Hospital Boston, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 438:873-7. 2005
  101. ncbi Visualization of protein interactions in living plant cells using bimolecular fluorescence complementation
    Michael Walter
    Institut fur Botanik und Botanischer Garten, Molekulare Entwicklungsbiologie der Pflanzen, Universitat Munster, Schlossplatz 4, 48149 Munster, Germany
    Plant J 40:428-38. 2004
    ..Consequently, the BiFC approach should significantly facilitate the visualization of the subcellular sites of protein interactions under conditions that closely reflect the normal physiological environment...

Research Grants71

  1. Physiological role of PRDM16 in brown fat development and energy balance
    Patrick Seale; Fiscal Year: 2011
    ..comparisons and share significant sequence similarity especially within the two conserved zinc-finger DNA/protein binding domains. We have therefore tested in our cell culture assays whether PRDM3 functions in brown adipogenesis...
  2. Functional Genomics of the Mitochondrial Proteome
    Dennis R Winge; Fiscal Year: 2011
    ..whose absence impaired mitochondrial respiratory function by determining mitochondrial localization and protein binding partners...
    Terence S Dermody; Fiscal Year: 2013
    ..abstract_text> ..
  4. BBP (Bone Morphogenetic Protein Binding Peptide) and Bone Healing
    SAMUEL SCOTT MURRAY; Fiscal Year: 2013
    ..We will also determine how the native bone protein spp24 (secreted phosphoprotein-24 kDa) inhibits BMP/TGF-b-dependent tumor cell growth. ..
  5. N-methanocarbathymidine (N-MCT) for the Treatment of Herpes and Pox Virus Infecti
    Aquilur Rahman; Fiscal Year: 2013
    ..plan to complete the remaining preclinical toxicity studies, drug formulation and stability studies, plasma protein binding and metabolism and the synthesis of additional quantities of non- GMP and GMP N-MCT to advance N-MCT to ..
  6. Molecular Biology of Human Erythrocyte Alpha Spectrin
    Patrick G Gallagher; Fiscal Year: 2013
    ..transcript composition, genomic organization, RNA polymerase II binding, transcription factor and regulatory protein binding, and histone architecture will provide detailed knowledge of erythrocyte membrane gene structure, function, ..
  7. Systems Analysis of Cardiac Chromatin Structure
    Thomas M Vondriska; Fiscal Year: 2013
    ..To be transcribed, a gene's local environment must be accessible for protein binding. The objective of this grant is to understand how this phenomenon is integrated on a genome- wide scale: how ..
  8. Liver Cell Membrane Protein-Expression and Function
    Allan W Wolkoff; Fiscal Year: 2012
    ..of vesicle-associated motors and regulatory factors;(Project 2) identification and characterization of protein binding partners for connexin 32 that may regulate its trafficking to and from the plasma membrane;(Project 3) ..
  9. Molecular mechanism of apolipoprotein binding to lipopolysaccharides
    PAUL MICHIEL WEERS; Fiscal Year: 2013
    ..The proposed research aims to understand the molecular basis of the protective role of apolipoproteins, thereby providing a foundation for improving the treatment of bacterial sepsis. ..
  10. Globin Gene Expression during Erythroid Differentiation
    Gordon D Ginder; Fiscal Year: 2010
    ..the following specific aims: 1) To characterize the protein components of erythroid cell methylated cytosine protein binding complex (MeCPC) that binds preferentially to methylated embryonic globin gene DMA sequences and verify the ..
  11. Analysis of the Human c-myc Gene Replication Origin
    Michael Leffak; Fiscal Year: 2012
    ..identified the replication origin 5'to the human c-myc oncogene, and we have shown that the structure, protein binding and function of the core c-myc replicator as a replication origin are the same at its endogenous chromosomal ..
  12. Molecular mechanism of antiangiogenic properties of gold nanoparticle
    Priyabrata Mukherjee; Fiscal Year: 2013
    ..Determine, in detail, pharmacological properties of gold nanoparticles, biodistribution, toxicity and plasma protein binding properties of AuNPs, and 2) Delineate the molecular mechanism of anti-angiogenic properties of AuNP in vivo...
  13. Design of CNS-Permeable Agents for the Treatment of Lipid Storage Diseases
    Scott D Larsen; Fiscal Year: 2010
    ..Evaluations of passive cellular permeability, P-gp mediated efflux and plasma protein binding will be used to predict efficient CNS penetration and to prioritize compounds for in vivo testing...
  14. Nuclear Receptor Networks in Human Disease
    Frances M Sladek; Fiscal Year: 2010
    ..These goals will be accomplished by pursuing three specific aims: 1) Use protein binding microarrays (PBMs) to determine the DNA binding specificity of select nuclear receptors on 10's of 1000&..
  15. Identification, Discovery, and Public Archiving of RNA Structural Motifs
    Shaojie Zhang; Fiscal Year: 2013
    ..the kink-turn motif is found in different kinds of non-coding RNAs and all of them are responsible for protein binding activities...
  16. Arrestin Regulation of CRF1 Signaling: Mechanisms for Stress Resilience and PTSD
    Richard L Hauger; Fiscal Year: 2013 strongly counterregulated by a GRK-[unreadable]arrestin2 desensitization mechanism, which inhibits G protein binding and internalizes the membrane receptor into cytosolic endosomes...
    ..of p/rds in OS morphogenesis and stability and understand the physiological implications of binary (direct) protein binding to this domain...
  18. Structural Basis for Synergistic Gene Expression by Runx1 and Ets1 Proteins
    Tahir H Tahirov; Fiscal Year: 2012
    ..and Mo-MLV enhancers, which represent examples of higher (>30 fold) and lower (~10) degrees of cooperative protein binding, as well as different spacing between Ets and Runx binding sites...
  19. Function of the chromosomal kinase haspin in mitosis
    JONATHAN M HIGGINS; Fiscal Year: 2010
    ..and overexpression to determine the influence of haspin on cohesin, chromosome passenger and heterochromatin protein binding at centromeres, and on patterns of histone modification...
  20. Role of a new polyomavirus in Merkel cell carcinoma
    Patrick S Moore; Fiscal Year: 2013
    ..Finally, we seek to generate a model system for MCV tumorigenesis that will be useful for drug screening and prevention. ..
  21. Experimental Therapeutics in Acute Leukemias
    William G Blum; Fiscal Year: 2010
    ..Given new laboratory data demonstrating critical differences between drug-protein binding in fetal bovine serum (FBS) vs...
  22. Cellular Retinoic Acid Binding Proteins: Functional Studies
    Lorraine J Gudas; Fiscal Year: 2013
    ..and 3 null cells;and deletion of DNA regulatory elements such as the Hoxa1 RARE, followed by analysis of PcG protein binding. We also propose a comparison of 3T3 cells with H-Ras transformed 3T3 cells to assess how an oncogenic ..
  23. Humanization of a mouse anti-OX40 monoclonal antibody to treat cancer
    Andrew D Weinberg; Fiscal Year: 2012
    ..further characterization of the mouse anti-human OX40 antibody variable regions for specificity of OX40 protein binding (ELISA and Western blot) and insertion of the variable regions from the antibody into an IgG backbone...
  24. Regulation of a Novel Trypanosome RNA Binding Protein by Arginine Methylation
    Kaylen Lott; Fiscal Year: 2013
    ..We will identify protein binding partners of TbMiz1 by mass spectrometry of tandem affinity purified wild type TbMiz1 and determine if arg ..
  25. A Diarylheptanoid Scaffold to Treat Taopathies
    Chad A Dickey; Fiscal Year: 2013
    ..The eADME studies will include metabolism in mouse and human liver microsomes, human plasma protein binding, water solubility testing, broad receptor and ion channel profiling including hERG, and initial ..
  26. Identifying novel small molecules for improved antifungal drug treatment
    Martha L Bulyk; Fiscal Year: 2012
    ..b>Protein binding microarrays (PBMs) will be used to characterize these compounds'ability to alter or inhibit zinc cluster ..
  27. Role of oxidative modifications to D-loop region in mTDNA replication in hypoxia
    Mykhaylo Ruchko; Fiscal Year: 2012
    ..ROS-mediated DNA damage and repair may serve to alter the topology of key DNA sequences to enable regulatory protein binding and facilitate transcription...
  28. Structure and Function of the B. anthracis Exosporium
    Charles L Turnbough; Fiscal Year: 2010
    ..3) Examine the assembly of the basal layer, focusing on protein binding partners and on enzymes that covalently cross-link and modify basal layer proteins...
  29. TOX, a Novel Regulator of Thymocyte Selection
    JONATHAN G KAYE; Fiscal Year: 2013
    ..Third, we propose state-of-the-art approaches to identify direct gene targets and protein binding partners of TOX, in an in vivo context of CD4 T cell development...
  30. Endocannabinoid modulation of pain-depressed behavior
    LAURA J SIMSELLEY; Fiscal Year: 2013
    ..pain, through the use of well- established neurochemical analyses such as mass spectrometry and [35S]GTPgS G-protein binding studies...
  31. Plerixafor/G-CSF with Sorafenib for Acute Myelogenous Leukemia with FLT3-ITD Muta
    MICHAEL W ANDREEFF; Fiscal Year: 2012
    ..has shown greater clinical activity in early studies than PKC-412 or CEP-701, probably because of lower protein binding. A study by Dr...
  32. Molecular basis for spotted fever group Rickettsia vector competence in ticks
    Kevin R Macaluso; Fiscal Year: 2013
    ..Studies will utilize paired tick tissues and SFG rickettsiae in comparative pull-down and protein binding assays...
  33. Barrier Insulators in Erythropoiesis
    Patrick G Gallagher; Fiscal Year: 2013
    ..After barrier insulators have been identified and functionally validated, histone architecture, regulatory protein binding, and genomic organization will be integrated and analyzed...
  34. Poly ADP-ribose Polymerase in Chromatin and Transcriptional Regulation
    Alexei V Tulin; Fiscal Year: 2012
    ..Aim 2. To determine the role of core histones in the PARP1 protein binding to chromatin. Aim 3...
  35. Relative Roles of HSP70 and HSP25 in the Modulation of Renal Injury
    Rajasree Sreedharan; Fiscal Year: 2010 well as the binding affinity of HSP70 for each of the integrity related proteins, immunoprecipitation, protein binding assays and surface plasmon resonance will be utilized...
  36. TGFBM2 in Development and Disease
    Rosemary J Akhurst; Fiscal Year: 2012
    ..mechanisms of interaction between TGFBM2 and TGFB signaling using gene transfection studies and in vitro protein binding studies...
  37. The competence regulon in Streptococcus mutans biofilms
    Dennis G Cvitkovitch; Fiscal Year: 2011
    ..The regulatory processes involved at modulating this network will be investigated using DNA-protein binding assays, protein-protein interactions and phosphorylation assays...
  38. Profilin-1 phosphorylation in neovascularization
    Yi Fan; Fiscal Year: 2013
    ..These studies wil provide important insight into the mechanisms controling post-MI neovascularization, and may lead to the development of novel therapeutic approaches for treating ischemic heart disease in humans. ..
  39. Transgenic Targeting of Vascular G Protein Signaling
    Karsten Peppel; Fiscal Year: 2010
    ..GRK-phosphorylated 7TMRs are inhibited from association with their normal heterotrimeric G protein binding partner via arrestin binding...
  40. Regulation of Plasmodium falciparum transcription
    Manuel Llinas; Fiscal Year: 2013
    ..Alternatively, a protein binding microarray (PBM) will be used to hybridize ApiAP2 proteins to a comprehensive collection of double stranded ..
  41. Role of Twisted Gastrulation in Osteoclastogenesis
    Rajaram Gopalakrishnan; Fiscal Year: 2013
    ..The overall objective of this project is to identify the cellular targets of Twsg1-disruption and characterize the signaling and molecular mechanisms by which Twsg1 inhibits osteoclastogenesis. ..
  42. Targeting myofibroblast activation in chronic fibrotic disease
    ARTHUR ROGER STRAUCH; Fiscal Year: 2011
    ..abstract_text> ..
    Charles E Samuel; Fiscal Year: 2013
    ..To delineate the importance of Sp1 and Sp3 protein binding to the novel 15-bp DNA element and upstream sites in IFN inducible as well as basal transcriptional activity...
  44. Novel Approaches for the synthesis of glycoprotein standards
    Geert Jan Boons; Fiscal Year: 2012
    ..will be employed for the development of a novel glycan array technology based on label-free detection of protein binding using surface enhanced Raman spectroscopy...
  45. Endothelial BK Channel Regulation by Caveolae Targeting
    Hon Chi Lee; Fiscal Year: 2010
    ..immunoprecipitation, immunofluorescence imaging, mutagenesis of hSIo and caveoline-1, and GST-fusion protein binding assays. Aim 2 is to determine the physiological interaction between BK channels and caveolae...
  46. Study the roles of RNA editing enzyme ADAR1 in the regulation of cell death
    Qingde Wang; Fiscal Year: 2010
    ..Aim #2: Determine the functional domain in ADAR1 that binds to IKK2 and regulates NF-kB activities. The protein binding domain of ADAR1 will be determined through expressions of mutated and truncated ADAR1 in mammalian cells and ..
  47. Aptamer Imaging: A Theranostic Approach to Treat Substance Abuse
    Philip K Liu; Fiscal Year: 2013
    ..ds) DNA aptamers with the sequence domain for AP-1 protein will function as decoys for endogenous AP-1 protein binding. The aptamers will be linked to an MR-visible contrast agent (superparamagnetic iron oxide nanoparticles-..
  48. ISS ChronosBH Fluorescence Lifetime Spectrometer
    FRANCISCO J BEZANILLA; Fiscal Year: 2010
    ..This allows direct determination of important parameters of protein-protein binding, complex formation, molecular contact, proximity and overall conformational changes...
    Alana V Beadell; Fiscal Year: 2013
    ..cerevisiae, Puf3p Puf4, and Puf5: a) Identify protein binding partners necessary for Puf-mediated translational repression of target mRNAs...
    Carolyn J Anderson; Fiscal Year: 2012
    ..Experiments proposed for Aim 3 will elucidate the copper protein binding partner for p53...
  51. Nuclear Receptor DNA Binding in Human Physiology and Disease
    Frances M Sladek; Fiscal Year: 2013
    ..determine the DNA binding specificity of a select group of NRs using an integrated approach based on protein binding microarrays (PBMs)...
  52. The AP2 factors required for Toxoplasma replication
    Michael W White; Fiscal Year: 2013
    ..expression for key cell cycle TgAP2 proteins, by discovering the promoters they regulate through whole-genome protein binding studies, and by validating the in vivo function of these proteins in parasite replication through the ..
  53. Fine tuning the catalytic cycle of kinesin motors
    FREDRICK JON KULL; Fiscal Year: 2013
  54. G protein regulation by ubiquitination
    MATTHEW PHILLIP TORRES; Fiscal Year: 2013 will be acquired in applied biophysical protein analysis (including structural, functional, and protein binding assays) through the Center for Structural Biology at the University of North Carolina at Chapel Hill (UNC)...
  55. Functional characterization of pathways regulated by schizophrenia gene TCF4
    JOSEPH LOUIE MCCLAY; Fiscal Year: 2013
    ..has been coupled with next generation sequencing (NGS), in a procedure known as ChIP-seq, to discover protein binding sites on a genome-wide level...
  56. Gene expression in M. tuberculosis
    Kathleen A McDonough; Fiscal Year: 2012
    ..ACG regulation at the molecular and biochemical levels, using promoter:reporter fusions, mutagenesis and DNA-protein binding assays...
  57. Localization of cisplatin and cisplatin-binding proteins in the inner ear
    Peter S Steyger; Fiscal Year: 2010
    ..The proposed research will enable the development of new strategies to prevent cochlear uptake of cisplatin and its derivates and subsequent ototoxic sequelae, particularly life-long deafness, tinnitus and vestibular deficits. ..
  58. Novel Compounds Targeting Bacterial PBPs
    LUIGI XERRI; Fiscal Year: 2013
    ..coli and K. pneumoniae). In addition, the early leads have good aqueous solubility (>1 mg/mL), low protein binding (<50% in mouse, dog, and human serum), high selectivity vs. mammalian serine-based enzymes (IC50 vs...
  59. Structural studies of tight junction proteins
    John M Flanagan; Fiscal Year: 2013
  60. Reovirus modulation of the cardiac innate response: Type I interferon and HSP25
    Barbara Sherry; Fiscal Year: 2013
    ..Results will provide significant new insights into functional domains and protein binding partners of participants in IFN signaling...
  61. Identification and Characterization of the Genetic Basis of PPCD
    ANTHONY JOHN ALDAVE; Fiscal Year: 2013
    ..proliferation, viability and motility of cultured corneal endothelial cells;and demonstrating using DNA-protein binding assays and transfection of an immortalized corneal endothelial cell line that ZEB1-mediated repression of ..
  62. Regulation of APP Pathway Gene Promoters in Alzheimer's
    Debomoy K Lahiri; Fiscal Year: 2011
    ..We will i) do functional and DNA-protein binding studies with promoter variants and ii) correlate promoter studies with levels of APP and Abeta...
    KENT GOLIC; Fiscal Year: 2002
    ..These candidates include the PRE sequences recognized by Polycomb Group proteins, polymers of the Zeste protein binding site, repeats of the AG dinucleotide recognized by the GAGA protein (the product of the Trithorax-like gene), ..
  64. Advancing lead dipiperidine compound into preclinical development
    Marina Protopopova; Fiscal Year: 2009
    ..the pharmacological properties of SQ609: stability evaluation in plasma and liver microsomes and plasma protein binding of SQ609;determination of pharmacokinetic parameters of SQ609 and bioavailability in mice following both IV ..
  65. Vaccinia Proteome Affinity Reagents From Phage Display
    Philip Felgner; Fiscal Year: 2005
    ..Weiss (Co-Investigator), will be used to hone binding affinity and specificity of vaccinia protein binding partners...
  66. Methods for the Development of Arrestin2 Inhibitors.
    Spiro Pavlopoulos; Fiscal Year: 2010
    ..Arrestin is a scaffold protein that can then recruit other protein binding partners and this leads to desensitization and internalization of the GPCR within the cell, processes that ..
    Paul Huber; Fiscal Year: 2000
    ..A similar analysis of the complex of ribosomal protein L5 with 5S rRNA will be undertaken. This affords the opportunity to examine the binding of two proteins, that exhibit no sequence identity, to congruent sites on an RNA molecule. ..
  68. Molecular Principles of FGF-HSGAG Interactions
    Ram Sasisekharan; Fiscal Year: 2006
    ..Our preliminary studies point out to exciting properties associated with HSGAG upon protein binding. While the overall helical structure is maintained in the protein-bound HSGAGs, a "kink" in the helical axis ..
    CHARLES MAYFIELD; Fiscal Year: 1999
    ..nuclease resistant oligonucleotides which form triplex DNA in a sequence specific manner and inhibits nuclear protein binding in the K-ras promoter...
  70. Small Molecule Inhibitors of HBV/HCV Induced Liver Diseases
    Surendra Dheer; Fiscal Year: 2009
    ..Successful completion of the proposed research will have identified a new drug candidate that can be further developed for prevention and treatment of HBV/HCV induced liver diseases and/or HCC in humans. ..
    JOHN KANALAS; Fiscal Year: 1993