cytoplasmic and nuclear receptors

Summary

Summary: Proteins in the cytoplasm or nucleus that specifically bind signaling molecules and trigger changes which influence the behavior of cells. The major groups are the steroid hormone receptors (RECEPTORS, STEROID), which usually are found in the cytoplasm, and the thyroid hormone receptors (RECEPTORS, THYROID HORMONE), which usually are found in the nucleus. Receptors, unlike enzymes, generally do not catalyze chemical changes in their ligands.

Top Publications

  1. ncbi Osteoprotegerin: a novel secreted protein involved in the regulation of bone density
    W S Simonet
    Department of Molecular Genetics, Amgen Inc, Thousand Oaks, California 91320, USA
    Cell 89:309-19. 1997
  2. ncbi Identification of a nuclear receptor for bile acids
    M Makishima
    Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235 9050, USA
    Science 284:1362-5. 1999
  3. ncbi Reciprocal regulation of inflammation and lipid metabolism by liver X receptors
    Sean B Joseph
    Howard Hughes Medical Institute, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California, USA
    Nat Med 9:213-9. 2003
  4. ncbi Osteoclast differentiation and activation
    William J Boyle
    Protein Pathways, Inc, Woodland Hills, California 91367, USA
    Nature 423:337-42. 2003
  5. ncbi A functional genomics strategy reveals Rora as a component of the mammalian circadian clock
    Trey K Sato
    Genomics Institute of the Novartis Research Foundation, 10675 John J Hopkins Drive, San Diego, California 92121, USA
    Neuron 43:527-37. 2004
  6. ncbi CRM1 is an export receptor for leucine-rich nuclear export signals
    M Fornerod
    European Molecular Biology Laboratory, Heidelberg, Germany
    Cell 90:1051-60. 1997
  7. pmc osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification
    N Bucay
    Department of Molecular Genetics, Amgen, Inc, Thousand Oaks, California 91320 1789, USA
    Genes Dev 12:1260-8. 1998
  8. ncbi Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network
    Angie L Bookout
    Department of Pharmacology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, 75390, USA
    Cell 126:789-99. 2006
  9. ncbi Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand
    Y Y Kong
    Amgen Institute, Toronto, Ontario, Canada
    Nature 402:304-9. 1999
  10. pmc Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL
    H Yasuda
    Research Institute of Life Science, Snow Brand Milk Products Co, Ltd, 519 Ishibashi machi, Shimotsuga gun, Tochigi 329 0512, Japan
    Proc Natl Acad Sci U S A 95:3597-602. 1998

Detail Information

Publications394 found, 100 shown here

  1. ncbi Osteoprotegerin: a novel secreted protein involved in the regulation of bone density
    W S Simonet
    Department of Molecular Genetics, Amgen Inc, Thousand Oaks, California 91320, USA
    Cell 89:309-19. 1997
    ..These data show that OPG can act as a soluble factor in the regulation of bone mass and imply a utility for OPG in the treatment of osteoporosis associated with increased osteoclast activity...
  2. ncbi Identification of a nuclear receptor for bile acids
    M Makishima
    Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235 9050, USA
    Science 284:1362-5. 1999
    ..These results demonstrate a mechanism by which bile acids transcriptionally regulate their biosynthesis and enterohepatic transport...
  3. ncbi Reciprocal regulation of inflammation and lipid metabolism by liver X receptors
    Sean B Joseph
    Howard Hughes Medical Institute, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California, USA
    Nat Med 9:213-9. 2003
    ..These findings identify LXRs as lipid-dependent regulators of inflammatory gene expression that may serve to link lipid metabolism and immune functions in macrophages...
  4. ncbi Osteoclast differentiation and activation
    William J Boyle
    Protein Pathways, Inc, Woodland Hills, California 91367, USA
    Nature 423:337-42. 2003
    ..Further study of this pathway is providing the molecular basis for developing therapeutics to treat osteoporosis and other diseases of bone loss...
  5. ncbi A functional genomics strategy reveals Rora as a component of the mammalian circadian clock
    Trey K Sato
    Genomics Institute of the Novartis Research Foundation, 10675 John J Hopkins Drive, San Diego, California 92121, USA
    Neuron 43:527-37. 2004
    ..These results suggest that opposing activities of the orphan nuclear receptors Rora and Rev-erb alpha, which represses Bmal1 expression, are important in the maintenance of circadian clock function...
  6. ncbi CRM1 is an export receptor for leucine-rich nuclear export signals
    M Fornerod
    European Molecular Biology Laboratory, Heidelberg, Germany
    Cell 90:1051-60. 1997
    ..We conclude that CRM1 is an export receptor for leucine-rich nuclear export signals and discuss a model for the role of RanGTP in CRM1 function and in nuclear export in general...
  7. pmc osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification
    N Bucay
    Department of Molecular Genetics, Amgen, Inc, Thousand Oaks, California 91320 1789, USA
    Genes Dev 12:1260-8. 1998
    ....
  8. ncbi Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network
    Angie L Bookout
    Department of Pharmacology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, 75390, USA
    Cell 126:789-99. 2006
    ..These data reveal a hierarchical transcriptional circuitry that extends beyond individual tissues to form a meganetwork governing physiology on an organismal scale...
  9. ncbi Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand
    Y Y Kong
    Amgen Institute, Toronto, Ontario, Canada
    Nature 402:304-9. 1999
    ..These results show that both systemic and local T-cell activation can lead to OPGL production and subsequent bone loss, and they provide a novel paradigm for T cells as regulators of bone physiology...
  10. pmc Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL
    H Yasuda
    Research Institute of Life Science, Snow Brand Milk Products Co, Ltd, 519 Ishibashi machi, Shimotsuga gun, Tochigi 329 0512, Japan
    Proc Natl Acad Sci U S A 95:3597-602. 1998
    ..ODF was found to be identical to TRANCE/RANKL, which enhances T-cell growth and dendritic-cell function. ODF seems to be an important regulator in not only osteoclastogenesis but also immune system...
  11. ncbi Inositol trisphosphate and calcium signalling
    M J Berridge
    AFRC Laboratory of Molecular Signalling, Department of Zoology, University of Cambridge, UK
    Nature 361:315-25. 1993
    ..Such a dynamic signalling pathway controls many cellular processes, including fertilization, cell growth, transformation, secretion, smooth muscle contraction, sensory perception and neuronal signalling...
  12. pmc Role of LXRs in control of lipogenesis
    J R Schultz
    Tularik Inc, South San Francisco, California 94080, USA
    Genes Dev 14:2831-8. 2000
    ..Complementary studies in cell culture and animals suggested that the increase in plasma lipids occurs via LXR-mediated induction of the sterol regulatory element-binding protein 1 (SREBP-1) lipogenic program...
  13. pmc Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue in the central conserved region
    N Kudo
    Department of Biotechnology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Bunkyo ku, Tokyo 113 8657, Japan
    Proc Natl Acad Sci U S A 96:9112-7. 1999
    ..These results show that the single cysteine residue determines LMB sensitivity and is selectively alkylated by LMB, leading to CRM1 inactivation...
  14. ncbi Exportin 1 (Crm1p) is an essential nuclear export factor
    K Stade
    Department of Biochemistry and Biophysics, University of California at San Francisco, 94143 0414, USA
    Cell 90:1041-50. 1997
    ..cerevisiae. The presented data are consistent with the conclusion that Crm1p is a carrier for the NES-mediated protein export pathway. We propose CRM1 be renamed exportin 1 (XPO1)...
  15. ncbi SIRT1 deacetylates and positively regulates the nuclear receptor LXR
    Xiaoling Li
    Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Mol Cell 28:91-106. 2007
    ..Our findings suggest that deacetylation of LXRs by SIRT1 may be a mechanism that affects atherosclerosis and other aging-associated diseases...
  16. ncbi Nuclear receptor expression links the circadian clock to metabolism
    Xiaoyong Yang
    Gene Expression Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell 126:801-10. 2006
    ....
  17. ncbi A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis
    B Goodwin
    Department of Molecular Endocrinology, Glaxo Wellcome Research and Development, Research Triangle Park, North Carolina 27709, USA
    Mol Cell 6:517-26. 2000
    ..This bile acid-activated regulatory cascade provides a molecular basis for the coordinate suppression of CYP7A1 and other genes involved in bile acid biosynthesis...
  18. ncbi The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator
    Nicolas Preitner
    Department of Molecular Biology, Sciences II, University of Geneva, 30, Quai Ernest Ansermet, CH 1211 4, Geneva, Switzerland
    Cell 110:251-60. 2002
    ..While REV-ERBalpha influences the period length and affects the phase-shifting properties of the clock, it is not required for circadian rhythm generation...
  19. ncbi Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro
    H Yasuda
    Research Institute of Life Science, Snow Brand Milk Products Co, Ltd, Tochigi, Japan
    Endocrinology 139:1329-37. 1998
    ..These results suggest that the sites are involved in cell-to-cell signaling between stromal cells and osteoclast progenitors and that OPG/OCIF inhibits osteoclastogenesis by interrupting the signaling through the sites...
  20. ncbi Identification of ligands for DAF-12 that govern dauer formation and reproduction in C. elegans
    Daniel L Motola
    Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
    Cell 124:1209-23. 2006
    ....
  21. ncbi A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors
    Y Kamei
    Howard Hughes Medical Institute, School of Medicine, University of California, San Diego, La Jolla, 92093 0648, USA
    Cell 85:403-14. 1996
    ....
  22. pmc Differential expression and activation of a family of murine peroxisome proliferator-activated receptors
    S A Kliewer
    Salk Institute for Biological Studies, La Jolla, CA
    Proc Natl Acad Sci U S A 91:7355-9. 1994
    ..These data suggest that tissue-specific responsiveness to peroxisome proliferators, including certain fatty acids, is in part a consequence of differential expression of multiple, pharmacologically distinct PPAR isoforms...
  23. pmc Protein ligands to HuR modulate its interaction with target mRNAs in vivo
    C M Brennan
    Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06536, USA
    J Cell Biol 151:1-14. 2000
    ..We discuss the possible role of these ligands upstream of HuR in pathways that govern the stability of ARE-containing mRNAs...
  24. pmc Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta
    J J Repa
    Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Genes Dev 14:2819-30. 2000
    ..Because this active form of SREBP-1c controls the transcription of genes involved in fatty acid biosynthesis, our results reveal a unique regulatory interplay between cholesterol and fatty acid metabolism...
  25. pmc The histone deacetylase-3 complex contains nuclear receptor corepressors
    Y D Wen
    Department of Chemistry, H Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, FL 33612, USA
    Proc Natl Acad Sci U S A 97:7202-7. 2000
    ..These results provide a possible molecular mechanism for HDAC3 regulation and argue that N-CoR is a platform in which distinct domains can interact with most of the known HDACs...
  26. ncbi The specificity of the CRM1-Rev nuclear export signal interaction is mediated by RanGTP
    P Askjaer
    Department of Molecular and Structural Biology, University of Aarhus, C F Mollers Alle, Building 130, DK 8000 Aarhus C, Denmark
    J Biol Chem 273:33414-22. 1998
    ..Our data are consistent with a model in which CRM1 is the nuclear export receptor for the Rev-RRE ribonucleoprotein complex and that RanGTP binds to a preformed Rev-CRM1 complex and specifies a functional interaction with the NES...
  27. ncbi Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation
    D L Lacey
    Department of Pathology, Amgen, Inc, Thousand Oaks, California 91320 1789, USA
    Cell 93:165-76. 1998
    ..These data suggest that OPGL is an osteoclast differentiation and activation factor. The effects of OPGL are blocked in vitro and in vivo by OPG, suggesting that OPGL and OPG are key extracellular regulators of osteoclast development...
  28. ncbi Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300
    H Chen
    Howard Hughes Medical Institute, School of Medicine, University of California at San Diego, La Jolla 92037, USA
    Cell 90:569-80. 1997
    ....
  29. pmc Identification of heme as the ligand for the orphan nuclear receptors REV-ERBalpha and REV-ERBbeta
    Srilatha Raghuram
    Department of Pharmacology and Center for Molecular Design, University of Virginia Health System, 1300 Jefferson Park Avenue, Charlottesville, Virginia 22908 0733, USA
    Nat Struct Mol Biol 14:1207-13. 2007
    ..Our results further indicate that heme regulation of REV-ERBs may link the control of metabolism and the mammalian clock...
  30. ncbi mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer
    P Tontonoz
    Dana Farber Cancer Institute, Boston, Massachusetts
    Genes Dev 8:1224-34. 1994
    ....
  31. ncbi Nuclear receptors--a perspective from Drosophila
    Kirst King-Jones
    Howard Hughes Medical Institute, Department of Human Genetics, University of Utah School of Medicine, 15 North 2030 East, Room 5100, Salt Lake City, Utah 84112 5331, USA
    Nat Rev Genet 6:311-23. 2005
    ..Here, we review recent breakthroughs in our understanding of D. melanogaster nuclear receptors, and interpret these results in light of findings from their evolutionarily conserved vertebrate homologues...
  32. pmc Synthetic LXR ligand inhibits the development of atherosclerosis in mice
    Sean B Joseph
    Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095 1662, USA
    Proc Natl Acad Sci U S A 99:7604-9. 2002
    ..These observations provide direct evidence for an atheroprotective effect of LXR agonists and support their further evaluation as potential modulators of human cardiovascular disease...
  33. pmc Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand
    H Hsu
    Department of Cell Biology, Amgen, Inc, One Amgen Center Drive, Thousand Oaks, CA 91320 1799, USA
    Proc Natl Acad Sci U S A 96:3540-5. 1999
    ..These data indicate that OPGL-induced osteoclastogenesis is directly mediated through RANK on osteoclast precursor cells...
  34. ncbi The photoreceptor-specific nuclear receptor Nr2e3 interacts with Crx and exerts opposing effects on the transcription of rod versus cone genes
    Guang Hua Peng
    Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO 63110, USA
    Hum Mol Genet 14:747-64. 2005
    ..Altogether, our findings suggest that Nr2e3 is a dual-function transcriptional regulator that acts in concert with Crx to promote and maintain the function of rod photoreceptors...
  35. ncbi Interaction between an integral protein of the nuclear envelope inner membrane and human chromodomain proteins homologous to Drosophila HP1
    Q Ye
    Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    J Biol Chem 271:14653-6. 1996
    ..LBR can interact with chromodomain proteins that are highly conserved in eukaryotic species and may function in the attachment of heterochromatin to the inner nuclear membrane in cells...
  36. pmc Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma
    Frederic Picard
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nature 429:771-6. 2004
    ..As a reduction in fat is sufficient to extend murine lifespan, our results provide a possible molecular pathway connecting calorie restriction to life extension in mammals...
  37. ncbi Delineation of mRNA export pathways by the use of cell-permeable peptides
    I E Gallouzi
    Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA
    Science 294:1895-901. 2001
    ....
  38. ncbi Altered constitutive expression of fatty acid-metabolizing enzymes in mice lacking the peroxisome proliferator-activated receptor alpha (PPARalpha)
    T Aoyama
    Department of Biochemistry, Shinshu University School of Medicine, Matsumoto, Nagano 390, Japan
    J Biol Chem 273:5678-84. 1998
    ....
  39. ncbi Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis
    C J Sinal
    Laboratory of Metabolism, Division of Basic Sciences, National Institutes of Health, Bethesda, Maryland 20892, USA
    Cell 102:731-44. 2000
    ..These data demonstrate that FXR/BAR is critical for bile acid and lipid homeostasis by virtue of its role as an intracellular bile acid sensor...
  40. ncbi The enzymes, regulation, and genetics of bile acid synthesis
    David W Russell
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390 9046, USA
    Annu Rev Biochem 72:137-74. 2003
    ..Inherited mutations that impair bile acid synthesis cause a spectrum of human disease; this ranges from liver failure in early childhood to progressive neuropathy in adults...
  41. pmc The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions
    J M Lehmann
    Department of Molecular Endocrinology, Glaxo Wellcome Research and Development, Research Triangle Park, North Carolina 27709, USA
    J Clin Invest 102:1016-23. 1998
    ..These findings provide a molecular explanation for the ability of disparate chemicals to induce CYP3A4 levels and, furthermore, provide a basis for developing in vitro assays to aid in predicting whether drugs will interact in humans...
  42. ncbi Identification of a nuclear receptor that is activated by farnesol metabolites
    B M Forman
    Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA
    Cell 81:687-93. 1995
    ..Intermediary metabolites have been recognized as transcriptional regulators in bacteria and yeast. Our results now suggest that metabolite-controlled intracellular signaling systems are utilized by higher organisms...
  43. ncbi Roles of PPARs in health and disease
    S Kersten
    Institut de Biologie Animale, Universite de Lausanne, Switzerland
    Nature 405:421-4. 2000
    ..Here we present the latest developments in the PPAR field, with particular emphasis on the physiological function of PPARs during various nutritional states, and the possible role of PPARs in several chronic diseases...
  44. ncbi Bile acids: natural ligands for an orphan nuclear receptor
    D J Parks
    Department of Molecular Biochemistry, Glaxo Wellcome Research and Development, Research Triangle Park NC, 27709, USA
    Science 284:1365-8. 1999
    ..These results provide evidence for a nuclear bile acid signaling pathway that may regulate cholesterol homeostasis...
  45. ncbi The versatility and universality of calcium signalling
    M J Berridge
    The Babraham Institute, Laboratory of Molecular Signalling, Babraham Hall, Babraham, Cambridge, CB2 4AT, UK
    Nat Rev Mol Cell Biol 1:11-21. 2000
    ..Exceeding its normal spatial and temporal boundaries can result in cell death through both necrosis and apoptosis...
  46. ncbi Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat
    O Braissant
    Institut de Biologie Animale, , , Switzerland
    Endocrinology 137:354-66. 1996
    ..PPAR-gamma is expressed predominantly in adipose tissue and the immune system. Our results suggest new potential directions to investigate the functions of the different PPAR subtypes...
  47. ncbi Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma
    R T Nolte
    Department of Structural Chemistry, Glaxo Wellcome Research and Development, Research Triangle Park, North Carolina 27709, USA
    Nature 395:137-43. 1998
    ....
  48. ncbi The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function
    J Torchia
    Howard Hughes Medical Institute, University of California, San Diego, La Jolla 92093 0648, USA
    Nature 387:677-84. 1997
    ..p/CIP, NCoA-1 and CBP all contain related leucine-rich charged helical interaction motifs that are required for receptor-specific mechanisms of gene activation, and allow the selective inhibition of distinct signal-transduction pathways...
  49. pmc Orphan nuclear receptor TLX recruits histone deacetylases to repress transcription and regulate neural stem cell proliferation
    GuoQiang Sun
    Neuroscience Division, Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA
    Proc Natl Acad Sci U S A 104:15282-7. 2007
    ..Taken together, these findings demonstrate a mechanism for neural stem cell proliferation through transcriptional repression of p21 and pten gene expression by TLX-HDAC interactions...
  50. ncbi 2-aminoethoxydiphenyl borate (2-APB) is a reliable blocker of store-operated Ca2+ entry but an inconsistent inhibitor of InsP3-induced Ca2+ release
    Martin D Bootman
    Laboratory of Molecular Signalling, The Babraham Institute, Babraham, Cambridge CB2 4AT, UK
    FASEB J 16:1145-50. 2002
    ..These data indicate that although it must be used with caution, 2-APB can be useful in probing certain aspects of Ca2+ signaling...
  51. pmc Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of diseased blood vessels
    Johannes Peter Stasch
    Institute of Cardiovascular Research, Bayer HealthCare, Wuppertal, Germany
    J Clin Invest 116:2552-61. 2006
    ....
  52. ncbi Expression and function of orphan nuclear receptor TLX in adult neural stem cells
    Yanhong Shi
    Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
    Nature 427:78-83. 2004
    ..TLX can silence glia-specific expression of the astrocyte marker GFAP in neural stem cells, suggesting that transcriptional repression may be crucial in maintaining the undifferentiated state of these cells...
  53. ncbi Calcium signaling mechanisms in T lymphocytes
    R S Lewis
    Department of Molecular and Cellular Physiology and Program in Immunology, Stanford University School of Medicine, Stanford, California 94305, USA
    Annu Rev Immunol 19:497-521. 2001
    ..The complexity of Ca(2+) signals contains a wealth of information that may help to instruct lymphocytes to choose between alternate fates in response to antigenic stimulation...
  54. ncbi Activation of PPARgamma coactivator-1 through transcription factor docking
    P Puigserver
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Science 286:1368-71. 1999
    ..Thus, transcription factor docking switches on the activity of a coactivator protein...
  55. ncbi CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and elimination pathways in mice
    Martin Wagner
    Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Medicine, Medical University Graz, Auenbruggerplatz 15, A 8036 Graz, Austria
    Hepatology 42:420-30. 2005
    ....
  56. ncbi Leucine-rich nuclear-export signals: born to be weak
    Ulrike Kutay
    Swiss Federal Institute of Technology ETH Zurich, Institute of Biochemistry, Schafmattstrasse 18, HPM F11 1, 8093 Zurich, Switzerland
    Trends Cell Biol 15:121-4. 2005
    ..This finding suggests that high-affinity NES binding to CRM1 impairs the efficient release of export complexes from the NPC, explaining why leucine-rich NESs have evolved to be weak...
  57. ncbi Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta
    Joyce J Repa
    Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 75390, USA
    J Biol Chem 277:18793-800. 2002
    ..The addition of ABCG5 and ABCG8 to the growing list of LXR target genes further supports the notion that LXRs serve as sterol sensors to coordinately regulate sterol catabolism, storage, efflux, and elimination...
  58. ncbi The importin-beta family member Crm1p bridges the interaction between Rev and the nuclear pore complex during nuclear export
    M Neville
    Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02254, USA
    Curr Biol 7:767-75. 1997
    ..Crm1p has recently been shown to contribute to nuclear export in vertebrate systems. Here, we have studied this mechanism of nuclear to cytoplasmic transport...
  59. pmc Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c
    Mitsuhiro Watanabe
    Institut de Génétique et Biologie Moléculaire et Cellulaire, CNRS INSERM ULP, Illkirch, France
    J Clin Invest 113:1408-18. 2004
    ..These results suggest that strategies aimed at increasing FXR activity and the repressive effects of SHP should be explored to correct hypertriglyceridemia...
  60. ncbi Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate
    N B Haider
    Howard Hughes Medical Institute, University of Iowa, Iowa City, Iowa, USA
    Nat Genet 24:127-31. 2000
    ..Expression of NR2E3 was limited to the outer nuclear layer of the human retina. Our results suggest that NR2E3 has a role in determining photoreceptor phenotype during human retinogenesis...
  61. pmc The C-terminal domain of TAP interacts with the nuclear pore complex and promotes export of specific CTE-bearing RNA substrates
    A Bachi
    European Molecular Biology Laboratory, Heidelberg, Germany
    RNA 6:136-58. 2000
    ....
  62. ncbi PHAX, a mediator of U snRNA nuclear export whose activity is regulated by phosphorylation
    M Ohno
    European Molecular Biology Laboratory, Heidelberg, Germany
    Cell 101:187-98. 2000
    ..PHAX phosphorylation is essential for export complex assembly while its dephosphorylation causes export complex disassembly. The compartmentalized PHAX phosphorylation cycle can contribute to the directionality of export...
  63. ncbi The mir-84 and let-7 paralogous microRNA genes of Caenorhabditis elegans direct the cessation of molting via the conserved nuclear hormone receptors NHR-23 and NHR-25
    Gabriel D Hayes
    Department of Genetics, Harvard Medical School and Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Development 133:4631-41. 2006
    ..The synergistic action of miRNA paralogs in development may be a general feature of the diversified miRNA gene family...
  64. ncbi 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma
    B M Forman
    Salk Institute for Biological Studies, La Jolla, California 92037, USA
    Cell 83:803-12. 1995
    ..These findings suggest a pivotal role for PPAR gamma and its endogenous ligand in adipocyte development and glucose homeostasis and as a target for intervention in metabolic disorders...
  65. pmc Nuclear hormone receptor NHR-49 controls fat consumption and fatty acid composition in C. elegans
    Marc R Van Gilst
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, USA
    PLoS Biol 3:e53. 2005
    ..Our findings in C. elegans provide novel insights into how NHR regulatory networks are coordinated to govern fat metabolism...
  66. ncbi PPARs and the complex journey to obesity
    Ronald M Evans
    Gene Expression Laboratory, Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
    Nat Med 10:355-61. 2004
    ..With molecular underpinnings now in place, new pharmacologic approaches to metabolic disease and new questions are emerging...
  67. pmc The Tlx gene regulates the timing of neurogenesis in the cortex
    Kristine Roy
    Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    J Neurosci 24:8333-45. 2004
    ..These studies indicate that tlx is an essential intrinsic regulator in the decision to proliferate or differentiate in the developing forebrain...
  68. ncbi Peroxisomal targeting signal-1 recognition by the TPR domains of human PEX5
    G J Gatto
    Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Nat Struct Biol 7:1091-5. 2000
    ..This structure reveals the molecular basis for PTS1 recognition and demonstrates a novel mode of TPR-peptide interaction...
  69. ncbi Gene expression profiling reveals a regulatory role for ROR alpha and ROR gamma in phase I and phase II metabolism
    Hong Soon Kang
    Cell Biology Section, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    Physiol Genomics 31:281-94. 2007
    ....
  70. ncbi Nuclear export of microRNA precursors
    Elsebet Lund
    Department of Biomolecular Chemistry, University of Wisconsin Medical School, Madison, WI 53706, USA
    Science 303:95-8. 2004
    ..Thus, Exp5 is key to miRNA biogenesis and may help coordinate nuclear and cytoplasmic processing steps...
  71. ncbi Automated yeast two-hybrid screening for nuclear receptor-interacting proteins
    Michael Albers
    PheneX Pharmaceuticals AG, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany
    Mol Cell Proteomics 4:205-13. 2005
    ....
  72. ncbi Liver X receptor signaling pathways in cardiovascular disease
    Peter Tontonoz
    Howard Hughes Medical Institute, University of California, Los Angeles School of Medicine, Box 951662, Los Angeles, California 90095 1662, USA
    Mol Endocrinol 17:985-93. 2003
    ..These observations identify the LXR pathway as a potential target for therapeutic intervention in human cardiovascular disease...
  73. ncbi Nuclear hormone receptors and gene expression
    A Aranda
    Instituto de Investigaciones Biomedicas Alberto Sols, Consejo Superior de Investigaciones Cientificas and Universidad Autonoma de Madrid, Madrid, Spain
    Physiol Rev 81:1269-304. 2001
    ....
  74. ncbi Xenobiotic stress induces hepatomegaly and liver tumors via the nuclear receptor constitutive androstane receptor
    Wendong Huang
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Endocrinol 19:1646-53. 2005
    ....
  75. ncbi Oxidized LDL regulates macrophage gene expression through ligand activation of PPARgamma
    L Nagy
    The Salk Institute of Biological Studies, Howard Hughes Medical Institute, La Jolla, California 92037, USA
    Cell 93:229-40. 1998
    ..These results suggest that PPARgamma may be a key regulator of foam cell gene expression...
  76. ncbi Peroxisome proliferator-activated receptor alpha activation modulates cellular redox status, represses nuclear factor-kappaB signaling, and reduces inflammatory cytokine production in aging
    M E Poynter
    Department of Pathology, University of Utah, Salt Lake City, Utah 84132, USA
    J Biol Chem 273:32833-41. 1998
    ..Our results suggest that PPARalpha and the genes under its control play a role in the evolution of oxidative stress excesses observed in aging...
  77. pmc Control of steroid, heme, and carcinogen metabolism by nuclear pregnane X receptor and constitutive androstane receptor
    Wen Xie
    Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Proc Natl Acad Sci U S A 100:4150-5. 2003
    ....
  78. ncbi Nuclear receptors and lipid physiology: opening the X-files
    A Chawla
    Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, Post Office Box 85800, San Diego, CA 92186 5800, USA
    Science 294:1866-70. 2001
    ....
  79. ncbi Molecular characterization of the role of orphan receptor small heterodimer partner in development of fatty liver
    Jiansheng Huang
    Department of Medicine, University of Kansas Medical Center, Kansas, KS 66160, USA
    Hepatology 46:147-57. 2007
    ..In addition, the pathways for hepatic lipid uptake and lipogenic program are also downregulated in OB(-/-)/SHP(-/-) mice, which may contribute to the decreased hepatic lipid content...
  80. ncbi Disruption of the nuclear hormone receptor RORalpha in staggerer mice
    B A Hamilton
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    Nature 379:736-9. 1996
    ..We propose a model based on these results, in which RORalpha interacts with the thyroid hormone signalling pathway to induce Purkinje-cell maturation...
  81. ncbi Antiproliferative effect of liver X receptor agonists on LNCaP human prostate cancer cells
    Junichi Fukuchi
    The Ben May Institute for Cancer Research and The Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois 60637, USA
    Cancer Res 64:7686-9. 2004
    ..Based on these results, modulation of the liver X receptor signaling pathway is a new target for controlling tumor cell proliferation; therefore, liver X receptor agonists may have utility as antitumorigenic agents...
  82. ncbi The coregulator exchange in transcriptional functions of nuclear receptors
    C K Glass
    Department of Cellular and Molecular Medicine, Department of Medicine, University of California, San Diego, La Jolla, California 92093 0651 USA
    Genes Dev 14:121-41. 2000
  83. ncbi The NGFI-B family of transcription factors regulates expression of 3beta-hydroxysteroid dehydrogenase type 2 in the human ovary
    Jon C Havelock
    Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Mol Hum Reprod 11:79-85. 2005
    ..Therefore, our data suggest that the NGFI-B may play a significant role in up-regulation of HSD3B2 that leads to the increase in progesterone production that is seen in granulosa cells at ovulation...
  84. ncbi Proteomic analysis of steady-state nuclear hormone receptor coactivator complexes
    Sung Yun Jung
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Endocrinol 19:2451-65. 2005
    ..We hope that the electronic availability of these data to the general scientific community will facilitate generation and testing of new hypotheses to further our understanding of nuclear receptor signaling and coactivator functions...
  85. pmc A novel pregnane X receptor-mediated and sterol regulatory element-binding protein-independent lipogenic pathway
    Jie Zhou
    Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15213, USA
    J Biol Chem 281:15013-20. 2006
    ..The cross-regulation of CD36 by PXR and PPARgamma suggests that this fatty acid transporter may function as a common target of orphan nuclear receptors in their regulation of lipid homeostasis...
  86. ncbi Nuclear-cytoplasmic shuttling of APC regulates beta-catenin subcellular localization and turnover
    B R Henderson
    Westmead Institute for Cancer Research, University of Sydney, Westmead Millenium Institute, Westmead NSW 2145, Australia
    Nat Cell Biol 2:653-60. 2000
    ..These findings suggest that wild-type APC controls the nuclear accumulation of beta-catenin by a combination of nuclear export and cytoplasmic degradation...
  87. pmc A pathway involving farnesoid X receptor and small heterodimer partner positively regulates hepatic sirtuin 1 levels via microRNA-34a inhibition
    Jiyoung Lee
    Department of Molecular and Integrative Physiology, University of Illinois, Urbana Champaign, Illinois 61801, USA
    J Biol Chem 285:12604-11. 2010
    ..Manipulation of this regulatory network may be useful for treating diseases of aging, such as metabolic disease and cancer...
  88. ncbi Molecular mechanisms of import of peroxisome-targeting signal type 2 (PTS2) proteins by PTS2 receptor Pex7p and PTS1 receptor Pex5pL
    Satoru Mukai
    Department of Biology, Faculty of Sciences, Kyushu University Graduate School, Fukuoka 812 8581, Japan
    J Biol Chem 281:37311-20. 2006
    ..Thus, the Pex7p-mediated PTS2 protein import shares most of the steps with the Pex5p-dependent PTS1 import machinery but is likely distinct at the cargo-releasing stage...
  89. pmc Nuclear hormone receptor regulation of microRNAs controls developmental progression
    Axel Bethke
    Huffington Center on Aging, Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Science 324:95-8. 2009
    ..These findings identify microRNAs as components of a hormone-coupled molecular switch that shuts off earlier developmental programs to allow for later ones...
  90. ncbi Steroidogenic factor 1: an essential mediator of endocrine development
    Keith L Parker
    Department of Internal Medicine and Pharmacology, University of Texas Southwestern Medical Center, Dallas 75390, USA
    Recent Prog Horm Res 57:19-36. 2002
    ..Finally, we highlight areas where additional studies are needed to expand our understanding of SF-1 action...
  91. pmc An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids
    W Xie
    Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 98:3375-80. 2001
    ..Therefore, we establish SXR and PXR as bile acid receptors and a role for the xenobiotic response in the detoxification of bile acids...
  92. ncbi An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita
    E Zanaria
    Universita di Pavia, Italy
    Nature 372:635-41. 1994
    ..DAX-1 encodes a new member of the nuclear hormone receptor superfamily displaying a novel DNA-binding domain. The DAX-1 product acts as a dominant negative regulator of transcription mediated by the retinoic acid receptor...
  93. ncbi Control of gene expression by fatty acids
    Jean Paul Pégorier
    Departement d Endocrinologie, Institut Cochin, INSERM U567, CNRS UMR8104, IFR Alfred Jost, Faculté de Médecine Cochin Port Royal, 24 rue du Faubourg Saint Jacques, 75014 Paris, France
    J Nutr 134:2444S-2449S. 2004
    ..The relative contribution of each transcription factor in fatty acid-induced positive or negative gene expression is discussed...
  94. pmc The Drosophila DHR96 nuclear receptor binds cholesterol and regulates cholesterol homeostasis
    Michael A Horner
    Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA
    Genes Dev 23:2711-6. 2009
    ..These studies define DHR96 as a central regulator of cholesterol homeostasis...
  95. ncbi Requirement for RORgamma in thymocyte survival and lymphoid organ development
    Z Sun
    Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine and Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA
    Science 288:2369-73. 2000
    ..Hence, RORgamma has critical functions in T cell repertoire selection and lymphoid organogenesis...
  96. ncbi Retinoid-related orphan receptor alpha controls the early steps of Purkinje cell dendritic differentiation
    Fatiha Boukhtouche
    Universite Pierre et Marie Curie PARIS6, Unité Mixte de Recherche 7102 Neurobiologie des Processus Adaptatifs, Centre National de la Recherche Scientifique, UMR 7102 NPA, Paris, F 75005, France
    J Neurosci 26:1531-8. 2006
    ..However, it does not seem to participate to the last stage of dendritic growth. This study identifies RORalpha as a nuclear receptor crucial for the control of dendritic remodeling during development...
  97. pmc Comparative analysis of function and interaction of transcription factors in nematodes: extensive conservation of orthology coupled to rapid sequence evolution
    Wilfried Haerty
    Department of Biology, McMaster University, Hamilton, ON L8S 4K1, Canada
    BMC Genomics 9:399. 2008
    ....
  98. ncbi Peroxisomes and oxidative stress
    Michael Schrader
    Department of Cell Biology and Cell Pathology, University of Marburg, Robert Koch Str 6, 35037 Marburg, Germany
    Biochim Biophys Acta 1763:1755-66. 2006
    ..In this respect the role of PPARalpha, which is highly activated in those mice, in prevention of oxidative stress deserves further investigation...
  99. pmc The orphan nuclear receptor ROR alpha is a negative regulator of the inflammatory response
    P Delerive
    INSERM U325, Departement d Atherosclerose, Institut Pasteur de Lille, France
    EMBO Rep 2:42-8. 2001
    ..Taken together, these data identify ROR alpha1 as a potential target in the treatment of chronic inflammatory diseases, including atherosclerosis and rheumatoid arthritis...
  100. ncbi Evidence for a role of CRM1 in signal-mediated nuclear protein export
    B Ossareh-Nazari
    Institut Curie CNRS Unité Mixte de Recherche 144, 26 Rue d Ulm, 75248 Paris Cedex 05, France
    Science 278:141-4. 1997
    ..Thus, the CRM1 protein could act as a NES receptor involved in nuclear protein export...
  101. ncbi A novel receptor-mediated nuclear protein import pathway
    V W Pollard
    Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia 19104 6148, USA
    Cell 86:985-94. 1996
    ..Furthermore, as hnRNP A1 likely participates in mRNA export, it raises the possibility that transportin is a mediator of this process as well...

Research Grants72

  1. Discovery metabolite profiling of the prolyl peptidases
    Alan Saghatelian; Fiscal Year: 2009
    ..Furthermore, the application of DMP to peptidases will demonstrate the generality of this approach for the future characterization of medically relevant enzymes and signaling pathways. ..
  2. Regulation of HSV-1 Gene Expression and Replication by Nuclear Hormone Receptors
    SHAOCHUNG VICTOR HSIA; Fiscal Year: 2013
    ..The long-term goal is to identify the regulatory mechanisms to assist in the development of novel therapeutic protocols for better treatments. ..
  3. Med1 in Liver Metabolism, Regeneration and Cancer
    Janardan K Reddy; Fiscal Year: 2013
    ....
  4. 5-HT transporter function: Interaction of hormones and antidepressants
    Alan Frazer; Fiscal Year: 2013
    ..Our basic research studies could have treatment implications for patients with either MDD and/or PTSD. ..
  5. Neuroprotection and Myelin Repair Mechanisms in Multiple Sclerosis
    Inderjit Singh; Fiscal Year: 2013
    ....
  6. Ethanol Regulation of Serum Glucocorticoid Kinase I
    BLAIR N COSTIN; Fiscal Year: 2012
    ..The work proposed here could shed light on molecular mechanisms underlying alcoholism and eventually have implications in the development of novel pharmacological agents for alcoholism or alcohol-related neurological disorders. ..
  7. Regulation of Bile Acid Synthesis by Nuclear Receptors
    John Y L Chiang; Fiscal Year: 2013
    ..The long-term objectives of this research are to elucidate the molecular mechanism of regulation of CYP7A1 and bile acid metabolism, and pathogenesis and treatment of metabolic diseases such as fatty liver disease, diabetes and obesity. ..
  8. Regulation of Hepatic SphK2 by Bile Acids: Effects on Lipid Metabolism
    HUIPING ROSE ZHOU; Fiscal Year: 2013
    ..Also, this study has potential impact on the identification and development of novel therapeutic targets for effective treatment of NAFLD and other related metabolic diseases. ..
  9. Regulation of NFkappaB activity by the Estrogen Receptor
    Kendall W Nettles; Fiscal Year: 2012
    ..We propose to use these synthetic compounds to understand the molecular details of this important anti-inflammatory pathway. ..
  10. Lipid Transport, Bile Acid Synthesis, and Cholesterol Homeostasis
    William M Pandak; Fiscal Year: 2013
    ..A better understanding of cell cholesterol, fatty acid, and bile acid metabolism is crucial in order to develop more effective therapies for lipid related disorders. ..
  11. Testing the efficacy of PGC-1alpha as a therapeutic target for Parkinson's diseas
    HANS BUELER; Fiscal Year: 2010
    ..abstract_text> ..
  12. Nuclear Receptor Coactivator Functions and Mechanisms
    Robert G Roeder; Fiscal Year: 2013
    ..By identification of new factors and mechanisms, and thus of novel therapeutic targets, these studies will have important implications for the control of obesity and muscle dystrophy. ..
  13. Excessive Copper Levels Disrupt Hepatic Nuclear Receptor Function
    Clavia Ruth Wooton-Kee; Fiscal Year: 2011
    ..This research specifically addresses the biological mechanisms relevant to human liver pathology and to Wilson's disease. ..
  14. Regulation of Rhox5 Transcriptional Elongation
    Marcy E Richardson; Fiscal Year: 2013
    ..The control of these two phenomena will be analyzed in the developmental and tissue-specific program that allows the expression of Rhox5 Pp in the mouse testis. ..
  15. Optimal Selective Thyroid Hormone Analogs for Metabolic Syndrome
    John D Baxter; Fiscal Year: 2010
    ..We will find drugs that will safely treat high cholesterol and obesity and work through one class of these proteins, thyroid hormone receptors. ..
  16. New pathways regulating bile acid homeostasis and cholestatic liver diseases
    Li Wang; Fiscal Year: 2013
    ..Fully defining the regulation of bile acid metabolism, including bile acid synthesis and catabolism, is essential for further advances in diagnosis, management, and prevention of cholestatic liver diseases. ..
  17. VASODEPRESSOR MECHANISMS IN HYPERTENSION
    Carlos M Ferrario; Fiscal Year: 2013
    ..Understanding the regulation of this system is vital to the prevention of cardiovascular disease as well as in the design of effective therapies to reduce the consequences of the disease. ..
  18. Regulation of Bile Acid Synthesis by Nuclear Receptors in Vivo
    Gregorio Gil; Fiscal Year: 2012
    ..The successful completion of this study will provide us with new insights into the molecular mechanisms involved in the regulation of bile acid biosynthesis. ..
  19. Inflammation and Immunosuppression in Lung Cancer
    Cong Yan; Fiscal Year: 2013
    ..Accomplishment of the proposed studies will elucidate the molecular mechanism by which the LAL/hormonal ligands/PPAR? axis controls anti-tumor adaptive immunity and pave the way for novel immunotherapy of lung cancer. ..
  20. Retinoid Mediated Protection Against Reactive Oxygen Species Induced Cytotoxicity
    Serrine S Lau; Fiscal Year: 2013
    ....
  21. Cicatricial Alopecia Research Symposium 2011: Lipids, Inflammation &Stem Cells
    Pratima Karnik; Fiscal Year: 2011
    ..The time is ripe for bringing national/international attention to this clinically challenging and biologically fascinating group of hair diseases. ..
  22. Ligands and cofactors required for RORgt function in the immune system
    Dan Littman; Fiscal Year: 2013
    ..Together, these studies will provide a better understanding of the mechanism of action of RORyt and will facilitate new strategies for therapy in autoimmune diseases. ..
  23. PROTRH GENE TRANSCRIPTION AND BIOSYNTHESIS BY LEPTIN
    EDUARDO NILLNI; Fiscal Year: 2009
    ..Aim #3. We will test the hypothesis that NPY down regulates the prohormone convertases 1 and 2 (PC1/2). Aim #4. We will identify the role of the egr-1 transcription factor in regulating PC2 by leptin and NPY ..
  24. CELLS PROCESSING HIGH DENSITY LIPOPROTEINS
    Salman Azhar; Fiscal Year: 2013
    ..Both bile acids and steroids are synthesized from SR-BI-mediated selectively delivered cholesterol, thus underscoring the relevance of understanding the cellular mechanisms controlling the functional expression of SR-BI. ..
  25. Reactivation of Fetal Gamma-globin Genes for the Treatment of Beta-globin Disorde
    Osamu Tanabe; Fiscal Year: 2010
    ..abstract_text> ..
  26. NOVEL HIGH THROUGHPUT PLATFORM FOR SCREENING CYTOCHROME P450 INDUCTION
    MARIA INES MORANO; Fiscal Year: 2013
    ....
  27. Mechanisms and Functions of Bimodally Targeted Cytochrome P450s to Mitochondria
    Narayan G Avadhani; Fiscal Year: 2012
    ..Finally, the role of mitochondria targeted CYPs in ischemia reperfusion injury will be studied using cell and animal models. ..
  28. Epigenic Control of ENaC Transcription and Sodium Transport
    Wenzheng Zhang; Fiscal Year: 2013
    ....
  29. Molecular Components Affecting Ocular Retinoid Homeostasis
    JOHANNES FRIEDERICH VONLINTIG; Fiscal Year: 2012
    ..abstract_text> ..
  30. Role of ABCG1 in lipid homeostasis, inflammation and innate immunity
    ELIZABETH JOANNA TARLING; Fiscal Year: 2013
    ....
  31. Structure-Based Design of Novel HNF4a Antagonists to Treat Metabolic Syndrome
    Arnold T Hagler; Fiscal Year: 2010
    ..To develop a drug to address this complex disease, we will take a novel approach, designing compounds that target the nuclear receptor HNF4a, which is involved in regulating all components of this syndrome. ..
  32. The PPAR-delta pathway in neural function and Hungtington's disease neuropatholog
    Albert R La Spada; Fiscal Year: 2013
    ....
  33. RNA Modification Enzymes: Methyltransferase/psi-synthase
    Robert M Stroud; Fiscal Year: 2012
    ..The importance of synthase activity is underlined by disorders such as sideroplastic anemia. The RNA MTase is a potential new drug target for anti-HIV therapy. ..
  34. PPARgamma and PPARgamma agonists in septic shock
    Basilia Zingarelli; Fiscal Year: 2013
    ..These studies may have an impact in developing novel therapies to decrease sepsis morbidity and mortality. ..
  35. SPATIAL REGULATION OF DEVELOPMENTAL GENE EXPRESSION
    Ronald M Evans; Fiscal Year: 2013
    ....
  36. METABOLIC EFFECTS OF THYROID HORMONE
    Herbert Samuels; Fiscal Year: 2009
    ..These studies should provide a more comprehensive picture of how these factors modulate NR function and other important biological processes in cells. ..
  37. Role of nuclear receptors in origin and differentiation of spermatozoa
    ADAM MICHAEL REITZEL; Fiscal Year: 2011
    ....
  38. BRCA1 and progesterone receptors in breast cancer
    Eva Y Lee; Fiscal Year: 2013
    ..How the progesterone receptor activity is regulated will be studied. The results will provide insights into breast cancer intervention and will have important implications for in breast cancer prevention and treatment. ..
  39. Lipid Activated Nuclear Receptors in Age-Related Macular Degeneration
    Goldis Malek; Fiscal Year: 2013
    ..Understanding the mechanisms underlying deposit formation and identifying signaling pathways key to disease initiation and progression will open up new avenues for therapeutic strategies in early 'dry'AMD. ..
  40. Genome-wide epigenetic control of circadian metabolism by heme receptor Rev-erb
    Mitchell A Lazar; Fiscal Year: 2010
    ....
  41. Protein methyltransferases as transcriptional coregulators
    Michael R Stallcup; Fiscal Year: 2013
    ..The same hormones also play important roles in the onset, progression, and treatment of many diseases, including cancer, diabetes, and heart disease. ..
  42. Nuclear Receptor Networks in Human Disease
    Frances M Sladek; Fiscal Year: 2010
    ..Our work will help bring us closer to an era of personalized medicine in which prevention, diagnosis and treatment are tailored to the individual patient, making them more effective and less costly. ..
  43. MOLECULAR BIOLOGY OF BILE ACID SYNTHESIS
    JOHN CHIANG; Fiscal Year: 2009
    ..Drugs targeting to nuclear receptor and signaling pathways, and miRNA antagomirs may be developed for treating metabolic liver diseases. ..
  44. Direct Regulation of Mitochondrial Transcription by Thyroid Hormone and Receptor
    MEGAN LYNN BESTWICK; Fiscal Year: 2012
    ..This research proposal aims to provide further understanding for the role of mitochondria in human disease and metabolic disorders such as diabetes. ..
  45. MOLECULAR BIOLOGY OF BILE ACID SYNTHESIS
    John Y L Chiang; Fiscal Year: 2013
    ..Drugs targeting to nuclear receptor and signaling pathways, and miRNA antagomirs may be developed for treating metabolic liver diseases. ..
  46. FUNCTIONAL ANALYSIS OF NUCLEAR RECEPTOR VARIANTS
    Curtis J Omiecinski; Fiscal Year: 2013
    ....
  47. Investigating the Mechanisms Regulating RORgamma Activity
    LAURA ANN SOLT; Fiscal Year: 2013
    ....
  48. CNS PPAR gamma and energy homeostasis
    HEIDI E KOCALIS; Fiscal Year: 2011
    ..If a role for PPARy in CNS controlled energy homeostasis is indicated, this will establish the brain as yet another target of PPARy agonist drugs. ..
  49. Developmental Regulation of Drug Processing Genes
    Xiao bo Zhong; Fiscal Year: 2013
    ....
  50. 5-HT transporter function: Interaction of antidepressants and hormones
    Alan Frazer; Fiscal Year: 2013
    ..The results obtained could have important implications for understanding treatment non-response in some women. ..
  51. Alpha actinin 4: its functions and regulation
    Hung Ying Kao; Fiscal Year: 2013
    ..We anticipate that our studies will uncover a previously underappreciated role for ACTN4 that is critical for podocyte functions and may have future therapeutic implications in kidney diseases. ..
  52. Structural Genomics of Orphan Nuclear Receptors
    H Eric Xu; Fiscal Year: 2013
    ....
  53. Regulation of Hepatic P450s by Anti-Cholesterol Drugs
    Thomas A Kocarek; Fiscal Year: 2013
    ..Therefore alternative anti-cholesterol drugs are needed. The public health relevance of this project is that it will increase our knowledge about the potential utility of a novel class of anti-cholesterol drugs. ..
  54. NR4A Orphan Receptors And Insulin Resistance
    W Timothy Garvey; Fiscal Year: 2012
    ..abstract_text> ..
  55. Discovery of novel anti-HBV compounds targeting host factors
    Pavel A Petukhov; Fiscal Year: 2013
    ....
  56. Airway epithelial repair in chronic bronchitis: novel signaling mechanisms
    Andreas Schmid; Fiscal Year: 2013
    ..This research is especially critical considering the continuing rise in airway diseases, especially related to smoking. The proposed research aims to elucidate critical parameters in airway epithelial cell repair. ..
  57. Treatment of Alcohol Induced Hepatic Injury with REV-ERB Ligands
    Thomas P Burris; Fiscal Year: 2013
    ..Furthermore, the proposed research has the potential for high impact since the compounds (or derivatives thereof) may be used clinically to treat ALD. ..
  58. Neurobiology of Aggression Co-morbidity in Mouse Model of Idic15 Autism
    Matthew P Anderson; Fiscal Year: 2013
    ..These studies provide a biological example and molecular mechanism for the hypermale brain in autism and explain increased aggression in idic15 autism. ..
  59. Airway epithelial repair in chronic bronchitis: novel signaling mechanisms
    Andreas Schmid; Fiscal Year: 2011
    ..This research is especially critical considering the continuing rise in airway diseases, especially related to smoking. The proposed research aims to elucidate critical parameters in airway epithelial cell repair. ..
  60. PPAR-Gamma's Role in Aberrant Adipogenesis and Fibrosis in Systemic Sclerosis
    BENJAMIN DOUGLAS KORMAN; Fiscal Year: 2013
    ..This work will help me to develop the knowledge and skills necessary to become an independent investigator and ultimately a future leader in rheumatology and the field of SSc research. ..
  61. Keystone Symposia on Cellular and Molecular Basis of Metabolic Disorders Series
    JAMES WAVELL AIKEN; Fiscal Year: 2013
    ..The meeting also discusses new technical advances designed to penetrate the molecular pathogenesis of Type 2 diabetes. ..
  62. TNIP1 risk haplotypes and immune endophenotypes
    Peter K Gregersen; Fiscal Year: 2013
    ..We will focus our studies particularly on the potential involvement of TNIP1 regulation of nuclear receptor function in the PPAR/RAR family. ..
  63. ANIMAL AND CELLULAR MODELS OF THYROID HORMONE RESISTANCE
    Gregory Brent; Fiscal Year: 1999
    ..This in vitro system will complement the in vivo studies and provide a model to study tissue specific gene regulation under more defined conditions. ..
  64. ANALYSIS OF THE ROLE OF GCNF IN SPERMATOGENESIS
    Austin Cooney; Fiscal Year: 1999
    ..Identification of the ligand can then be used to generate agonists and antagonists of GCNF function which can be used to used to modulate its activity and treat idiopathic sterility where applicable. ..
  65. Fibroblast Growth Factor Regulation in the Pancreas
    Sam Holmstrom; Fiscal Year: 2009
    ..Therefore, understanding the hormonal regulation of exocrine pancreas function by FGF15 may yield new therapeutic avenues with high potential for pharmacological intervention by targeting membrane receptors. ..
  66. NUCLEAR HORMONE ACTION--ROLE OF UBIQUITIN PATHWAYS
    Zafar Nawaz; Fiscal Year: 2003
    ..Of the NEDD8 pathway as a co-activator of NHRs and to characterize this role in nuclear hormone receptor co-activation. ..
  67. NR4A Regulation of Organ Morphogenesis
    CHRISTOPHER GISSENDANNER; Fiscal Year: 2009
    ..This project will determine the genetic functions of NR4A in organ formation, an area of NR4A biology for which little is currently known. ..
  68. Analyses of a Non tumorigenic Teratocarcinoma Cell Line
    Paulette McCormick; Fiscal Year: 2005
    ..These studies will contribute significantly to our understanding of stem cell biology, embryonic development and cancer. ..
  69. THYROID/RETINOIC ACID RECEPTOR INTERACTING PROTEINS
    Mukul Mathur; Fiscal Year: 2004
    ..We will also specify the region on the DNA binding domain of these receptors where these three proteins interact. ..
  70. Imaging Nuclear Receptor LRH-1 in Functional Transcriptional Assemblies
    Robert J Fletterick; Fiscal Year: 2010
    ....
  71. The control of growth and metabolism by effectors of the TOR signaling pathway
    Michael Lehmann; Fiscal Year: 2007
    ..It will thus improve our under- standing of how nutrient sensing is linked to fat metabolism and help paving the way for treatments of obesity-related (type 2) diabetes and other diseases. [unreadable] [unreadable] [unreadable]..
  72. ORPHAN NUCLEAR RECEPTORS IN DEVELOPMENT AND DISEASE
    Gary Hammer; Fiscal Year: 2000
    ..In this application, I propose to examine the molecular mechanisms of SF-1 gene activation and begin to characterize the role of SF-1 in adrenal cortical cell lineage determination. ..