endoplasmic reticulum

Summary

Summary: A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)

Top Publications

  1. doi The unfolded protein response: from stress pathway to homeostatic regulation
    Peter Walter
    Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA
    Science 334:1081-6. 2011
  2. pmc Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death
    M C Wei
    Howard Hughes Medical Institute, Departments of Pathology and Medicine, Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Science 292:727-30. 2001
  3. pmc CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum
    Stefan J Marciniak
    Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA
    Genes Dev 18:3066-77. 2004
  4. pmc XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response
    Ann Hwee Lee
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    Mol Cell Biol 23:7448-59. 2003
  5. pmc Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state
    K D McCullough
    Cell Stress and Aging Section, Laboratory of Biological Chemistry, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224 6825, USA
    Mol Cell Biol 21:1249-59. 2001
  6. ncbi Signal integration in the endoplasmic reticulum unfolded protein response
    David Ron
    The Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA
    Nat Rev Mol Cell Biol 8:519-29. 2007
  7. pmc Autophagy is activated for cell survival after endoplasmic reticulum stress
    Maiko Ogata
    Division of Molecular and Cellular Biology, Department of Anatomy, Faculty of Medicine, University of Miyazaki, Kihara 5200, Kiyotake, Miyazaki 889 1692, Japan
    Mol Cell Biol 26:9220-31. 2006
  8. pmc STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx
    Jen Liou
    Department of Molecular Pharmacology, Stanford University Medical School, California 94305, USA
    Curr Biol 15:1235-41. 2005
  9. pmc Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress
    Ira Tabas
    Department of Medicine, Anatomy and Cell Biology, Columbia University, New York, NY 10032, USA
    Nat Cell Biol 13:184-90. 2011
  10. ncbi A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress
    Michael Boyce
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Science 307:935-9. 2005

Detail Information

Publications292 found, 100 shown here

  1. doi The unfolded protein response: from stress pathway to homeostatic regulation
    Peter Walter
    Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA
    Science 334:1081-6. 2011
    The vast majority of proteins that a cell secretes or displays on its surface first enter the endoplasmic reticulum (ER), where they fold and assemble. Only properly assembled proteins advance from the ER to the cell surface...
  2. pmc Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death
    M C Wei
    Howard Hughes Medical Institute, Departments of Pathology and Medicine, Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Science 292:727-30. 2001
    ..function: staurosporine, ultraviolet radiation, growth factor deprivation, etoposide, and the endoplasmic reticulum stress stimuli thapsigargin and tunicamycin...
  3. pmc CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum
    Stefan J Marciniak
    Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA
    Genes Dev 18:3066-77. 2004
    Unfolded and malfolded client proteins impose a stress on the endoplasmic reticulum (ER), which contributes to cell death in pathophysiological conditions...
  4. pmc XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response
    Ann Hwee Lee
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    Mol Cell Biol 23:7448-59. 2003
    ..unfolded protein response (UPR) protects the cell against the stress of misfolded proteins in the endoplasmic reticulum (ER)...
  5. pmc Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state
    K D McCullough
    Cell Stress and Aging Section, Laboratory of Biological Chemistry, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224 6825, USA
    Mol Cell Biol 21:1249-59. 2001
    ..is a highly stress-inducible gene that is robustly expressed following disruption of homeostasis in the endoplasmic reticulum (ER) (so-called ER stress)...
  6. ncbi Signal integration in the endoplasmic reticulum unfolded protein response
    David Ron
    The Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA
    Nat Rev Mol Cell Biol 8:519-29. 2007
    The endoplasmic reticulum (ER) responds to the accumulation of unfolded proteins in its lumen (ER stress) by activating intracellular signal transduction pathways - cumulatively called the unfolded protein response (UPR)...
  7. pmc Autophagy is activated for cell survival after endoplasmic reticulum stress
    Maiko Ogata
    Division of Molecular and Cellular Biology, Department of Anatomy, Faculty of Medicine, University of Miyazaki, Kihara 5200, Kiyotake, Miyazaki 889 1692, Japan
    Mol Cell Biol 26:9220-31. 2006
    Eukaryotic cells deal with accumulation of unfolded proteins in the endoplasmic reticulum (ER) by the unfolded protein response, involving the induction of molecular chaperones, translational attenuation, and ER-associated degradation, ..
  8. pmc STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx
    Jen Liou
    Department of Molecular Pharmacology, Stanford University Medical School, California 94305, USA
    Curr Biol 15:1235-41. 2005
    ..proteins have a single transmembrane region with a putative Ca(2+) binding domain in the lumen of the endoplasmic reticulum. Ca(2+) store depletion led to a rapid translocation of STIM1 into puncta that accumulated near the plasma ..
  9. pmc Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress
    Ira Tabas
    Department of Medicine, Anatomy and Cell Biology, Columbia University, New York, NY 10032, USA
    Nat Cell Biol 13:184-90. 2011
    The ability to respond to perturbations in endoplasmic reticulum (ER) function is a fundamentally important property of all cells, but ER stress can also lead to apoptosis...
  10. ncbi A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress
    Michael Boyce
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Science 307:935-9. 2005
    ..In a screen for small molecules that protect cells from endoplasmic reticulum (ER) stress, we identified salubrinal, a selective inhibitor of cellular complexes that dephosphorylate ..
  11. pmc One step at a time: endoplasmic reticulum-associated degradation
    Shruthi S Vembar
    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    Nat Rev Mol Cell Biol 9:944-57. 2008
    Protein folding in the endoplasmic reticulum (ER) is monitored by ER quality control (ERQC) mechanisms...
  12. pmc Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum
    Elizabeth L Axe
    Signalling Programme, Babraham Institute, Babraham, Cambridge, England, UK
    J Cell Biol 182:685-701. 2008
    ..Autophagosome formation is known to require phosphatidylinositol 3-phosphate (PI(3)P) and occurs near the endoplasmic reticulum (ER), but the exact mechanisms are unknown...
  13. ncbi Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes
    Umut Ozcan
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Harvard University, Boston, MA 02115, USA
    Science 313:1137-40. 2006
    b>Endoplasmic reticulum (ER) stress is a key link between obesity, insulin resistance, and type 2 diabetes...
  14. pmc Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity
    Suneng Fu
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    Nature 473:528-31. 2011
    The endoplasmic reticulum (ER) is the main site of protein and lipid synthesis, membrane biogenesis, xenobiotic detoxification and cellular calcium storage, and perturbation of ER homeostasis leads to stress and the activation of the ..
  15. pmc TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death
    Nobumichi Ohoka
    Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho, Nagoya, Japan
    EMBO J 24:1243-55. 2005
    ..TRB3 is induced by various forms endoplasmic reticulum (ER) stress later than CHOP...
  16. ncbi Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls
    R J Kaufman
    Department of Biological Chemistry and Howard Hughes Medical Institute, The University of Michigan Medical Center, Ann Arbor, Michigan 48109 0650 USA
    Genes Dev 13:1211-33. 1999
  17. ncbi Perk is essential for translational regulation and cell survival during the unfolded protein response
    H P Harding
    Department of Medicine, The Kaplan Cancer Center, New York University School of Medicine, New York 10016, USA
    Mol Cell 5:897-904. 2000
    Malfolded proteins in the endoplasmic reticulum (ER) inhibit translation initiation...
  18. ncbi Molecular chaperones and protein quality control
    Bernd Bukau
    Zentrum fur Molekulare Biologie, Universitat Heidelberg, 69120 Heidelberg, Germany
    Cell 125:443-51. 2006
    ..describe the removal of aggregates from the cytosol; reveal mechanisms for protein quality control in the endoplasmic reticulum; and provide new insight into two classes of molecular chaperones, the Hsp70 system and the AAA+ (Hsp100) ..
  19. ncbi ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs
    J Ye
    Department of Molecular Genetics, University of Texas, Southwestern Medical Center, Dallas, TX 75390, USA
    Mol Cell 6:1355-64. 2000
    ATF6 is a membrane-bound transcription factor that activates genes in the endoplasmic reticulum (ER) stress response...
  20. pmc STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling
    Hiroki Ishikawa
    Department of Medicine and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida 33136, USA
    Nature 455:674-8. 2008
    ..It comprises five putative transmembrane regions, predominantly resides in the endoplasmic reticulum and is able to activate both NF-kappaB and IRF3 transcription pathways to induce expression of type I ..
  21. ncbi Translational control is required for the unfolded protein response and in vivo glucose homeostasis
    D Scheuner
    Howard Hughes Medical Institute, University of Michigan Medical Center, 48109, Ann Arbor, MI, USA
    Mol Cell 7:1165-76. 2001
    The accumulation of unfolded protein in the endoplasmic reticulum (ER) attenuates protein synthesis initiation through phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2alpha) at Ser51...
  22. ncbi The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol
    Y Ye
    Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 414:652-6. 2001
    In eukaryotic cells, incorrectly folded proteins in the endoplasmic reticulum (ER) are exported into the cytosol and degraded by the proteasome. This pathway is co-opted by some viruses...
  23. ncbi ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals
    Jingshi Shen
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Dev Cell 3:99-111. 2002
    ATF6 is an endoplasmic reticulum (ER) stress-regulated transmembrane transcription factor that activates the transcription of ER molecular chaperones...
  24. pmc Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress
    K Haze
    HSP Research Institute, Kyoto Research Park, Shimogyo ku, Kyoto 600 8813, Japan
    Mol Biol Cell 10:3787-99. 1999
    ..response (UPR) controls the levels of molecular chaperones and enzymes involved in protein folding in the endoplasmic reticulum (ER). We recently isolated ATF6 as a candidate for mammalian UPR-specific transcription factor...
  25. ncbi ER stress and diseases
    Hiderou Yoshida
    Department of Biophysics, Graduate School of Science, Kyoto University, Japan
    FEBS J 274:630-58. 2007
    Proteins synthesized in the endoplasmic reticulum (ER) are properly folded with the assistance of ER chaperones. Malfolded proteins are disposed of by ER-associated protein degradation (ERAD)...
  26. ncbi Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes
    Umut Ozcan
    Department of Genetics and Complex Diseases, Harvard Medical School, Boston, MA 02115, USA
    Science 306:457-61. 2004
    ..Using cell culture and mouse models, we show that obesity causes endoplasmic reticulum (ER) stress...
  27. pmc Endoplasmic reticulum stress triggers autophagy
    Tomohiro Yorimitsu
    Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Biol Chem 281:30299-304. 2006
    ..In this study, we demonstrate a new pathway for the induction of autophagy. In the endoplasmic reticulum (ER), accumulation of misfolded proteins causes stress and activates the unfolded protein response to ..
  28. doi Endoplasmic reticulum-mitochondria contacts: function of the junction
    Ashley A Rowland
    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, 80309, USA
    Nat Rev Mol Cell Biol 13:607-25. 2012
    The most well-characterized organelle contact sites are those between the endoplasmic reticulum (ER) and mitochondria...
  29. doi A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation
    Mitsuko Hayashi-Nishino
    Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567 0047, Japan
    Nat Cell Biol 11:1433-7. 2009
    ..Using electron microscopy, we show that, in mammalian culture cells, the endoplasmic reticulum (ER) associates with early autophagic structures called isolation membranes (IMs)...
  30. doi COPII and the regulation of protein sorting in mammals
    Giulia Zanetti
    Department of Molecular and Cell Biology and Howard Hughes Medical Institute, University of California at Berkeley, Berkeley, California 94720, USA
    Nat Cell Biol 14:20-8. 2012
    Secretory proteins are transported to the Golgi complex in vesicles that bud from the endoplasmic reticulum. The cytoplasmic coat protein complex II (COPII) is responsible for cargo sorting and vesicle morphogenesis...
  31. doi Endoplasmic reticulum dysfunction in neurological disease
    Benoit D Roussel
    Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
    Lancet Neurol 12:105-18. 2013
    b>Endoplasmic reticulum (ER) dysfunction might have an important part to play in a range of neurological disorders, including cerebral ischaemia, sleep apnoea, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, the ..
  32. ncbi 3D tomography reveals connections between the phagophore and endoplasmic reticulum
    Päivi Ylä-Anttila
    University of Helsinki, Department of Biological and Environmental Sciences, Division of Biochemistry, Helsinki, Finland
    Autophagy 5:1180-5. 2009
    Autophagosomes have been reported to form in the vicinity of the endoplasmic reticulum (ER)...
  33. pmc Orchestrating the unfolded protein response in health and disease
    Randal J Kaufman
    Department of Biological Chemistry, Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor 48109 0650, USA
    J Clin Invest 110:1389-98. 2002
  34. ncbi The role for endoplasmic reticulum stress in diabetes mellitus
    Decio L Eizirik
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, Route de Lennik, 808 CP 618, 1070 Brussels, Belgium
    Endocr Rev 29:42-61. 2008
    Accumulating evidence suggests that endoplasmic reticulum (ER) stress plays a role in the pathogenesis of diabetes, contributing to pancreatic beta-cell loss and insulin resistance...
  35. ncbi CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry
    M Vig
    Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    Science 312:1220-3. 2006
    ..Although overexpression of CRACM1 did not affect CRAC currents, RNAi-mediated knockdown disrupted its activation. CRACM1 could be the CRAC channel itself, a subunit of it, or a component of the CRAC signaling machinery...
  36. pmc XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease
    Arthur Kaser
    Division of Gastroenterology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
    Cell 134:743-56. 2008
    ..The transcription factor XBP1, a key component of the endoplasmic reticulum (ER) stress response, is required for development and maintenance of secretory cells and linked to JNK ..
  37. ncbi Endoplasmic reticulum stress and oxidative stress: a vicious cycle or a double-edged sword?
    Jyoti D Malhotra
    Howard Hughes Medical Institute and Departments of Biological Chemistry and Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
    Antioxid Redox Signal 9:2277-93. 2007
    The endoplasmic reticulum (ER) is a well-orchestrated protein-folding machine composed of protein chaperones, proteins that catalyze protein folding, and sensors that detect the presence of misfolded or unfolded proteins...
  38. pmc The endoplasmic reticulum and the unfolded protein response
    Jyoti D Malhotra
    Howard Hughes Medical Institute, Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, MI 48109, United States
    Semin Cell Dev Biol 18:716-31. 2007
    The endoplasmic reticulum (ER) is the site where proteins enter the secretory pathway...
  39. pmc Mediators of endoplasmic reticulum stress-induced apoptosis
    Eva Szegezdi
    Department of Biochemistry and National Centre for Biomedical Engineering Science, National University of Ireland, University Road, Galway, Ireland
    EMBO Rep 7:880-5. 2006
    The efficient functioning of the endoplasmic reticulum (ER) is essential for most cellular activities and survival. Conditions that interfere with ER function lead to the accumulation and aggregation of unfolded proteins...
  40. pmc Endoplasmic reticulum stress and the inflammatory basis of metabolic disease
    Gokhan S Hotamisligil
    Department of Genetics and Complex Diseases, Broad Institute of Harvard and MIT, Harvard School of Public Health, Boston, MA 02115, USA
    Cell 140:900-17. 2010
    The endoplasmic reticulum (ER) is the major site in the cell for protein folding and trafficking and is central to many cellular functions...
  41. pmc Unfolded proteins are Ire1-activating ligands that directly induce the unfolded protein response
    Brooke M Gardner
    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA
    Science 333:1891-4. 2011
    The unfolded protein response (UPR) detects the accumulation of unfolded proteins in the endoplasmic reticulum (ER) and adjusts the protein-folding capacity to the needs of the cell...
  42. ncbi Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta
    T Nakagawa
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 403:98-103. 2000
    ..Others, such as caspase-9, mediate apoptotic signals after mitochondrial damage. Stress in the endoplasmic reticulum (ER) can also result in apoptosis...
  43. doi Biochemically distinct vesicles from the endoplasmic reticulum fuse to form peroxisomes
    Adabella van der Zand
    Cellular Protein Chemistry, Faculty of Science, Utrecht University, NL 3584 CH Utrecht, The Netherlands
    Cell 149:397-409. 2012
    ..Peroxisomes are unique because they acquire their lipids and membrane proteins from the endoplasmic reticulum (ER), whereas they import their matrix proteins directly from the cytosol...
  44. pmc Mechanisms determining the morphology of the peripheral ER
    Yoko Shibata
    Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Cell 143:774-88. 2010
    The endoplasmic reticulum (ER) consists of the nuclear envelope and a peripheral network of tubules and membrane sheets...
  45. ncbi A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol
    Yihong Ye
    Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 429:841-7. 2004
    Elimination of misfolded proteins from the endoplasmic reticulum (ER) by retro-translocation is an important physiological adaptation to ER stress...
  46. ncbi XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor
    H Yoshida
    Graduate School of Biostudies, Kyoto University, Kyoto 606 8304, Japan
    Cell 107:881-91. 2001
    In yeast, the transmembrane protein kinase/endoribonuclease Ire1p activated by endoplasmic reticulum stress cleaves HAC1 mRNA, leading to production of the transcription factor Hac1p that activates the unfolded protein response (UPR)...
  47. pmc Road to ruin: targeting proteins for degradation in the endoplasmic reticulum
    Melanie H Smith
    Department of Cellular and Molecular Pharmacology, Graduate Group in Biophysics and Howard Hughes Medical Institute, University of California San Francisco, CA 94158, USA
    Science 334:1086-90. 2011
    Some nascent proteins that fold within the endoplasmic reticulum (ER) never reach their native state...
  48. ncbi Cellular response to endoplasmic reticulum stress: a matter of life or death
    M Boyce
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell Death Differ 13:363-73. 2006
    The proper functioning of the endoplasmic reticulum (ER) is critical for numerous aspects of cell physiology...
  49. doi Protein folding stress in neurodegenerative diseases: a glimpse into the ER
    Soledad Matus
    Center for Molecular Studies of Cell, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile
    Curr Opin Cell Biol 23:239-52. 2011
    ..pathological feature of protein misfolding disorders, highlighting perturbations in the homeostasis of the endoplasmic reticulum (ER)...
  50. pmc Signaling cell death from the endoplasmic reticulum stress response
    Gordon C Shore
    Department of Biochemistry and Goodman Cancer Center, McGill University, Montreal, Quebec, H3G 1Y6, Canada
    Curr Opin Cell Biol 23:143-9. 2011
    Inability to meet protein folding demands within the endoplasmic reticulum (ER) activates the unfolded protein response (UPR), a signaling pathway with both adaptive and apoptotic outputs...
  51. pmc Endoplasmic reticulum protein quality control and its relationship to environmental stress responses in plants
    Jian Xiang Liu
    State Key Laboratory of Genetic Engineering, Institute of Plant Biology, School of Life Sciences, Fudan University, Shanghai, China 200433
    Plant Cell 22:2930-42. 2010
    The endoplasmic reticulum (ER) has a sophisticated quality control (QC) system to eliminate improperly folded proteins from the secretory pathway...
  52. pmc ER chaperones in mammalian development and human diseases
    Min Ni
    Department of Biochemistry and Molecular Biology, USC Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, 1441 Eastlake Ave, Los Angeles, CA 90089 9176, United States
    FEBS Lett 581:3641-51. 2007
    The field of endoplasmic reticulum (ER) stress in mammalian cells has expanded rapidly during the past decade, contributing to understanding of the molecular pathways that allow cells to adapt to perturbations in ER homeostasis...
  53. ncbi ER stress and the unfolded protein response
    Martin Schroder
    School of Biological and Biomedical Sciences, University of Durham, Durham DH1 3LE, UK
    Mutat Res 569:29-63. 2005
    ..g. Alzheimer's disease. Expression of mutant proteins disrupts protein folding in the endoplasmic reticulum (ER), causes ER stress, and activates a signaling network called the unfolded protein response (UPR)...
  54. pmc Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex
    Denise Egger
    Institute for Medical Microbiology, University of Basel, CH 4003 Basel, Switzerland
    J Virol 76:5974-84. 2002
    ..Expression of the entire HCV polyprotein gave rise to membrane budding into rough endoplasmic reticulum vacuoles, to the membranous web, and to tightly associated vesicles often surrounding the membranous web...
  55. ncbi Coupling endoplasmic reticulum stress to the cell death program
    R V Rao
    Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA
    Cell Death Differ 11:372-80. 2004
    The endoplasmic reticulum (ER) regulates protein synthesis, protein folding and trafficking, cellular responses to stress and intracellular calcium (Ca(2+)) levels...
  56. pmc Viral reorganization of the secretory pathway generates distinct organelles for RNA replication
    Nai Yun Hsu
    Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA
    Cell 141:799-811. 2010
    ..These findings reveal how RNA viruses can selectively exploit specific elements of the host to form specialized organelles where cellular phosphoinositide lipids are key to regulating viral RNA replication...
  57. ncbi ER stress (PERK/eIF2alpha phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation
    Y Kouroku
    Division of Development, National Institute of Neuroscience, 4 1 1 Ogawahigashi machi, Kodaira, Tokyo 187 8502, Japan
    Cell Death Differ 14:230-9. 2007
    Expanded polyglutamine 72 repeat (polyQ72) aggregates induce endoplasmic reticulum (ER) stress-mediated cell death with caspase-12 activation and vesicular formation (autophagy)...
  58. pmc Oxidative protein folding in eukaryotes: mechanisms and consequences
    Benjamin P Tu
    Howard Hughes Medical Institute, Department of Cellular and Molecular Pharmacology, University of California, San Francisco, 94143, USA
    J Cell Biol 164:341-6. 2004
    The endoplasmic reticulum (ER) provides an environment that is highly optimized for oxidative protein folding...
  59. ncbi Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-beta, and Bcl-2
    Maria Høyer-Hansen
    Apoptosis Department and Centre for Genotoxic Stress Research, Institute of Cancer Biology, Danish Cancer Society, 2100 Copenhagen, Denmark
    Mol Cell 25:193-205. 2007
    ..Thus, an increase in the [Ca(2+)](c) serves as a potent inducer of macroautophagy and as a target for the antiautophagy action of ER-located Bcl-2...
  60. pmc An ER-mitochondria tethering complex revealed by a synthetic biology screen
    Benoît Kornmann
    Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, CA 94158, USA
    Science 325:477-81. 2009
    ..To uncover components involved in mitochondria/endoplasmic reticulum (ER) junctions, we screened for mutants that could be complemented by a synthetic protein designed to ..
  61. pmc HCV causes chronic endoplasmic reticulum stress leading to adaptation and interference with the unfolded protein response
    Emmanuelle Merquiol
    Liver Unit, Division of Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel
    PLoS ONE 6:e24660. 2011
    The endoplasmic reticulum (ER) is the cellular site for protein folding. ER stress occurs when protein folding capacity is exceeded...
  62. pmc The conserved GTPase Gem1 regulates endoplasmic reticulum-mitochondria connections
    Benoît Kornmann
    Department of Biochemistry and Biophysics and Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA
    Proc Natl Acad Sci U S A 108:14151-6. 2011
    Mitochondria are connected to the endoplasmic reticulum (ER) through specialized protein complexes...
  63. ncbi S-nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration
    Takashi Uehara
    Center for Neuroscience and Aging, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Nature 441:513-7. 2006
    Stress proteins located in the cytosol or endoplasmic reticulum (ER) maintain cell homeostasis and afford tolerance to severe insults...
  64. pmc Retrotranslocation of a misfolded luminal ER protein by the ubiquitin-ligase Hrd1p
    Pedro Carvalho
    Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Cell 143:579-91. 2010
    Misfolded, luminal endoplasmic reticulum (ER) proteins are retrotranslocated into the cytosol and degraded by the ubiquitin/proteasome system...
  65. doi Composition and three-dimensional architecture of the dengue virus replication and assembly sites
    Sonja Welsch
    Department of Molecular Virology, University of Heidelberg, Im Neuenheimer Feld 345, Heidelberg D 69120, Germany
    Cell Host Microbe 5:365-75. 2009
    ..microscopy, we find Dengue virus (DENV)-induced vesicles, convoluted membranes, and virus particles to be endoplasmic reticulum (ER)-derived, and we detect double-stranded RNA, a presumed marker of RNA replication, inside virus-..
  66. ncbi Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1
    F Urano
    Skirball Institute of Biomolecular Medicine, Departments of Medicine, Cell Biology and the Kaplan Cancer Center, New York University Medical School, New York, NY 10016, USA
    Science 287:664-6. 2000
    Malfolded proteins in the endoplasmic reticulum (ER) induce cellular stress and activate c-Jun amino-terminal kinases (JNKs or SAPKs)...
  67. ncbi Intracellular functions of N-linked glycans
    A Helenius
    Institute of Biochemistry, , , , Switzerland
    Science 291:2364-9. 2001
    ..arise when blocks of 14 sugars are added cotranslationally to newly synthesized polypeptides in the endoplasmic reticulum (ER)...
  68. pmc Initiation and execution of lipotoxic ER stress in pancreatic beta-cells
    Daniel A Cunha
    Laboratory of Experimental Medicine, Universite Libre de Bruxelles, Brussels, Belgium
    J Cell Sci 121:2308-18. 2008
    ..of pancreatic beta-cells and might contribute to beta-cell loss in type 2 diabetes via the induction of endoplasmic reticulum (ER) stress...
  69. ncbi Regulated translation initiation controls stress-induced gene expression in mammalian cells
    H P Harding
    Skirball Institute of Biomolecular Medicine The Department of Medicine, Kaplan Cancer Center New York University School of Medicine, New York, NY 10016, USA
    Mol Cell 6:1099-108. 2000
    ..Mammalian cells thus utilize an ancient pathway to regulate gene expression in response to diverse stress signals...
  70. pmc ER tubules mark sites of mitochondrial division
    Jonathan R Friedman
    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA
    Science 334:358-62. 2011
    ..The endoplasmic reticulum (ER) and mitochondria exhibit tightly coupled dynamics and have extensive contacts...
  71. ncbi A class of membrane proteins shaping the tubular endoplasmic reticulum
    Gia K Voeltz
    Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Cell 124:573-86. 2006
    ..achieved? We have used an in vitro system to address the mechanism by which the tubular network of the endoplasmic reticulum (ER) is generated and maintained...
  72. 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...
  73. pmc Endoplasmic reticulum stress in liver disease
    Harmeet Malhi
    Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, Rochester, MN, USA
    J Hepatol 54:795-809. 2011
    The unfolded protein response (UPR) is activated upon the accumulation of misfolded proteins in the endoplasmic reticulum (ER) that are sensed by the binding immunoglobulin protein (BiP)/glucose-regulated protein 78 (GRP78)...
  74. pmc Comprehensive characterization of genes required for protein folding in the endoplasmic reticulum
    Martin C Jonikas
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA
    Science 323:1693-7. 2009
    Protein folding in the endoplasmic reticulum is a complex process whose malfunction is implicated in disease and aging...
  75. doi Endoplasmic reticulum stress plays a central role in development of leptin resistance
    Lale Ozcan
    Division of Endocrinology, Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    Cell Metab 9:35-51. 2009
    ..Here, we show that increased endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) in the hypothalamus of obese mice ..
  76. pmc Stringent requirement for HRD1, SEL1L, and OS-9/XTP3-B for disposal of ERAD-LS substrates
    Riccardo Bernasconi
    Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland
    J Cell Biol 188:223-35. 2010
    Sophisticated quality control mechanisms prolong retention of protein-folding intermediates in the endoplasmic reticulum (ER) until maturation while sorting out terminally misfolded polypeptides for ER-associated degradation (ERAD)...
  77. pmc The unfolded protein response: a pathway that links insulin demand with beta-cell failure and diabetes
    Donalyn Scheuner
    Department of Biological Chemistry, and Howard Hughes Medical Institute, The University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
    Endocr Rev 29:317-33. 2008
    The endoplasmic reticulum (ER) is the entry site into the secretory pathway for newly synthesized proteins destined for the cell surface or released into the extracellular milieu...
  78. doi ERAD substrates: which way out?
    Daniel N Hebert
    Department of Biochemistry and Molecular Biology, Program in Molecular and Cellular Biology, University of Massachusetts, Amherst, MA 01003, USA
    Semin Cell Dev Biol 21:526-32. 2010
    Global folding of polypeptides entering the endoplasmic reticulum (ER) starts as soon as they emerge from the narrow Sec61 translocon...
  79. ncbi Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes
    D R Laybutt
    Diabetes and Obesity Research Program, Garvan Institute of Medical Research, St Vincent s Hospital, Sydney, NSW, Australia
    Diabetologia 50:752-63. 2007
    ..We investigated whether endoplasmic reticulum (ER) stress is necessary for lipid-induced apoptosis in beta cells and also whether ER stress is present ..
  80. pmc Multiple mechanism-mediated retention of a defective brassinosteroid receptor in the endoplasmic reticulum of Arabidopsis
    Zhi Hong
    Department of Molecular, Cellular, and Developmental Biology, University of Michigan, An Arbor, Michigan 48109 1048, USA
    Plant Cell 20:3418-29. 2008
    b>Endoplasmic reticulum-mediated quality control (ERQC) is a well-studied process in yeast and mammals that retains and disposes misfolded/unassembled polypeptides...
  81. ncbi Entry of protein toxins into mammalian cells by crossing the endoplasmic reticulum membrane: co-opting basic mechanisms of endoplasmic reticulum-associated degradation
    J M Lord
    Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK
    Curr Top Microbiol Immunol 300:149-68. 2005
    ..protein toxins reach their substrates in the cytosol of mammalian cells by retro-translocation from the endoplasmic reticulum (ER)...
  82. doi Protein quality control in the cytosol and the endoplasmic reticulum: brothers in arms
    Alexander Buchberger
    Department of Biochemistry, Biocenter, University of Wurzburg, Am Hubland, 97074 Wurzburg, Germany
    Mol Cell 40:238-52. 2010
    ..Here, we compare the protein quality control systems of the eukaryotic cytosol and the endoplasmic reticulum, focusing on the principles of damage recognition, the triage decisions between chaperone-mediated ..
  83. pmc The critical roles of endoplasmic reticulum chaperones and unfolded protein response in tumorigenesis and anticancer therapies
    B Luo
    Department of Biochemistry and Molecular Biology, University of Southern California USC Norris Comprehensive Cancer Center, Keck School of Medicine of USC, Los Angeles, CA 90089 9176, USA
    Oncogene 32:805-18. 2013
    ..Therefore, enhanced endoplasmic reticulum (ER) activity is required to facilitate the folding, assembly and transportation of membrane and secretory ..
  84. pmc Regulated Ire1-dependent decay of messenger RNAs in mammalian cells
    Julie Hollien
    Department of Biology, University of Utah, Salt Lake City, UT 84112, USA
    J Cell Biol 186:323-31. 2009
    Maintenance of endoplasmic reticulum (ER) function is achieved in part through Ire1 (inositol-requiring enzyme 1), a transmembrane protein activated by protein misfolding in the ER...
  85. pmc The delicate balance between secreted protein folding and endoplasmic reticulum-associated degradation in human physiology
    Christopher J Guerriero
    Department of Biological Sciences, University of Pittsburgh, A320 Langley Hall, Pittsburgh, PA 15260, USA
    Physiol Rev 92:537-76. 2012
    ..folding of proteins in the secretory pathway adds another layer to the protein folding "problem," as the endoplasmic reticulum maintains a unique chemical environment within the cell...
  86. pmc OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD
    John C Christianson
    Department of Biological Sciences and Bio X Program, Stanford University, Lorry Lokey Bldg, 337 Campus Drive, Stanford, CA 94305, USA
    Nat Cell Biol 10:272-82. 2008
    ..These data suggest that XTP3-B and OS-9 are components of distinct, partially redundant, quality control surveillance pathways that coordinate protein folding with membrane dislocation and ubiquitin conjugation in mammalian cells...
  87. pmc Autophagy requires endoplasmic reticulum targeting of the PI3-kinase complex via Atg14L
    Kohichi Matsunaga
    Department of Genetics, Graduate School of Medicine, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
    J Cell Biol 190:511-21. 2010
    ..Atg14L is specific to this autophagy complex and localizes to the endoplasmic reticulum (ER)...
  88. ncbi The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients
    P Marchetti
    Department of Endocrinology and Metabolism, Metabolic Unit, Ospedale Cisanello, University of Pisa, Via Paradisa 2, 56100, Pisa, Italy
    Diabetologia 50:2486-94. 2007
    Pancreatic beta cells have highly developed endoplasmic reticulum (ER) due to their role in insulin secretion...
  89. pmc Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha
    I Novoa
    Skirball Institute of Biomolecular Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA
    J Cell Biol 153:1011-22. 2001
    ..isolated and found to attenuate CHOP (also known as GADD153) activation by both protein malfolding in the endoplasmic reticulum, and amino acid deprivation...
  90. pmc Defining the human deubiquitinating enzyme interaction landscape
    Mathew E Sowa
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Cell 138:389-403. 2009
    ..link Dubs to diverse processes, including protein turnover, transcription, RNA processing, DNA damage, and endoplasmic reticulum-associated degradation...
  91. ncbi The mammalian unfolded protein response
    Martin Schroder
    School of Biological and Biomedical Sciences, University of Durham, Durham DH1 3LE, United Kingdom
    Annu Rev Biochem 74:739-89. 2005
    In the endoplasmic reticulum (ER), secretory and transmembrane proteins fold into their native conformation and undergo posttranslational modifications important for their activity and structure...
  92. ncbi The unfolded protein response: a stress signaling pathway critical for health and disease
    Kezhong Zhang
    Department of Biological Chemistry, Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
    Neurology 66:S102-9. 2006
    The endoplasmic reticulum (ER) is an intracellular organelle consisting of a membranous labyrinth network that extends throughout the cytoplasm of the cell and is contiguous with the nuclear envelope...
  93. pmc The endoplasmic reticulum enzyme DGAT2 is found in mitochondria-associated membranes and has a mitochondrial targeting signal that promotes its association with mitochondria
    Scot J Stone
    Department of Biochemistry, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E5, Canada
    J Biol Chem 284:5352-61. 2009
    ..We found that DGAT2 expressed in cultured cells localizes to the endoplasmic reticulum (ER) under basal conditions...
  94. ncbi Roles of CHOP/GADD153 in endoplasmic reticulum stress
    S Oyadomari
    Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860 8556, Japan
    Cell Death Differ 11:381-9. 2004
    b>Endoplasmic reticulum (ER) is the site of synthesis and folding of secretory proteins. Perturbations of ER homeostasis affect protein folding and cause ER stress...
  95. ncbi An integrated stress response regulates amino acid metabolism and resistance to oxidative stress
    Heather P Harding
    Skirball Institute, New York University School of Medicine, New York, NY 10016, USA
    Mol Cell 11:619-33. 2003
    Eukaryotic cells respond to unfolded proteins in their endoplasmic reticulum (ER stress), amino acid starvation, or oxidants by phosphorylating the alpha subunit of translation initiation factor 2 (eIF2alpha)...
  96. ncbi ER stress triggers apoptosis by activating BH3-only protein Bim
    Hamsa Puthalakath
    The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    Cell 129:1337-49. 2007
    b>Endoplasmic reticulum (ER) stress caused by misfolded proteins or cytotoxic drugs can kill cells and although activation of this pathway has been implicated in the etiology of certain degenerative disorders its mechanism remains ..
  97. pmc Protein quality control in the ER: balancing the ubiquitin checkbook
    Jasper H L Claessen
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA
    Trends Cell Biol 22:22-32. 2012
    Protein maturation in the endoplasmic reticulum (ER) is subject to stringent quality control. Terminally misfolded polypeptides are usually ejected into the cytoplasm and targeted for destruction by the proteasome...
  98. pmc CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum
    H Zinszner
    Skirball Institute of Biomolecular Medicine, the Departments of Medicine, Cell Biology, and the Kaplan Cancer Center, New York University NYU Medical Center, New York, New York 10016 USA
    Genes Dev 12:982-95. 1998
    Cellular stress, particularly in response to toxic and metabolic insults that perturb function of the endoplasmic reticulum (ER stress), is a powerful inducer of the transcription factor CHOP...
  99. ncbi Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase
    H P Harding
    Skirball Institute of Biomolecular Medicine, Department of Medicine, NYU School of Medicine, New York 10016, USA
    Nature 397:271-4. 1999
    ..level of eukaryotic initiation factor-2alpha (eIF2alpha) in response to a stress signal from the endoplasmic reticulum (ER)...
  100. pmc Endoplasmic reticulum stress: cell life and death decisions
    Chunyan Xu
    The Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Clin Invest 115:2656-64. 2005
    ..Important roles for ER-initiated cell death pathways have been recognized for several diseases, including hypoxia, ischemia/reperfusion injury, neurodegeneration, heart disease, and diabetes...
  101. ncbi The endoplasmic reticulum: a multifunctional signaling organelle
    Michael J Berridge
    Laboratory of Molecular Signaling, The Babraham Institute, Cambridge CB2 4AT, Babraham, UK
    Cell Calcium 32:235-49. 2002
    The endoplasmic reticulum (ER) is a multifunctional signaling organelle that controls a wide range of cellular processes such as the entry and release of Ca(2+), sterol biosynthesis, apoptosis and the release of arachidonic acid (AA)...

Research Grants76

  1. NIH Director's Pioneer Award
    Junying Yuan; Fiscal Year: 2009
    ..No Abstract provided ..
  2. H1R Signaling and Immune Deviation in EAE
    Cory Teuscher; Fiscal Year: 2013
    ..surface expression was substantially lower than H1RS, with H1RR exhibiting intracellular retention in the endoplasmic reticulum (ER)...
  3. Air Pollution on Adiposity and Vascular Dysfunction: White or Brown Matters?
    Qinghua Sun; Fiscal Year: 2013
    ..5) pollution induces adipose dysfunction via reactive oxygen species (ROS)-dependent activation of endoplasmic reticulum (ER) stress and potentiation of insulin resistance. To achieve this goal, we first assess PM2...
  4. Regulation of ER stress-induced cell death
    Randal J Kaufman; Fiscal Year: 2013
    ..UPR is an adaptive signaling pathway to promote cell survival upon accumulation of unfolded protein in the endoplasmic reticulum (ER)...
  5. Translational Machinery in Stress Signaling and Tumor Suppression
    THOMAS J contact BEGLEY; Fiscal Year: 2010
    ..Regulation of the translation machinery during toxic conditions, such as endoplasmic reticulum (ER) stress, can arrest cell growth and promote the repair of damage or promote cell death...
  6. Role for Na,K-ATPase in Nucleoplasmic Calcium Homeostasis
    Craig Gatto; Fiscal Year: 2010
    ..work revealed for the first time that the Na pump is completely functional once assembled within the endoplasmic reticulum. However, the potential physiological role of this intracellular activity remained a mystery...
  7. MODULATION OF IFN ACTION VIA NOVEL REGULATORY FACTORS
    DHAN V KALVAKOLANU; Fiscal Year: 2013
    ..Notably, Activating transcription factor 6 (ATF6), a key regulator of endoplasmic reticulum-dependent stress responses, appears to regulate DAPK1 expression...
  8. ER stress: role in myocyte apoptosis and myocardial remodeling
    Krishna Singh; Fiscal Year: 2013
    ..The endoplasmic reticulum (ER or sarcoplasmic reticulum in cardiac myocytes) is a principal site for protein folding, calcium ..
  9. Nitric Oxide in Hemodialysis AV Fistula Maturation
    Richard A Cohen; Fiscal Year: 2010
    ..will quantify NO release, measure reactive oxygen species, determine the redox status of the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA), and assess intracellular Ca2+...
  10. Cellular and Animal Models of FUS Mutations in ALS
    Eric J Huang; Fiscal Year: 2013
    ..FUS protein aggregates that are associated with markedly disorganized intracellular organelles, including endoplasmic reticulum (ER) and mitochondria...
  11. Regulation of K-Ras by a Farnesyl-electrostatic Switch
    MARK REID PHILIPS; Fiscal Year: 2013
    ..in release of K-Ras from the plasma membrane and association with intracellular membranes, including the endoplasmic reticulum (ER), Golgi apparatus and the outer mitochondrial membrane...
  12. Regulation of LPS-mediated HMGB1 Release by Poly (ADP-ribose) Polymerase-1
    RAJESH K ANEJA; Fiscal Year: 2013
    ..HMGB1 lacks a secretory signal peptide;therefore, it cannot be secreted via the endoplasmic reticulum-Golgi system. The newly synthesized HMGB1 undergoes extensive post-translational modifications, e.g...
  13. Mechanism(s) of Alcoholic Pancreatitis
    Bhupendra S Kaphalia; Fiscal Year: 2011
    ..and pancreatic lipids, fatty acid ethyl esters (FAEEs, nonoxidative lipid metabolites of ethanol) and endoplasmic reticulum (ER) stress in hepatic alcohol dehydrogenase (ADH)-deficient (ADH-) vs. normal ADH (ADH+) deer mice fed 3...
  14. MEMBRANES OF THE DENTAL PATHOGEN STREPTOCOCCUS MUTANS
    L Jeannine Brady; Fiscal Year: 2013
    ..all living cells and involved in insertion and secretion of proteins into and through the cytoplasmic or endoplasmic reticulum membrane. Until it was demonstrated otherwise in S. mutans, the SRP pathway was considered essential. In S...
  15. High throughput screen for selective inhibitors of cyclophilin B
    Richard J Bram; Fiscal Year: 2013
    ..The endoplasmic reticulum (ER) resident prolyl isomerase Cyclophilin B (CypB) is highly up-regulated in multiple types of cancers...
  16. A fully validated assay to identify activators of ERSR in human glioma cells: ide
    Maurizio Grimaldi; Fiscal Year: 2012
    ..amount of preliminary data indicating that glioma cells are sensible to cell death induced by triggering endoplasmic reticulum stress response (ERSR)...
  17. Cell stress, development, and stimulant-induced behavior: Regulation by GSK3
    Marjelo A Mines; Fiscal Year: 2012
    ..b>Endoplasmic reticulum (ER) stress, resulting from the accumulation of misfolded proteins, is associated with many diseases and ..
  18. Hepatic Steatosis and ER Stress-Inducible Transcription Factor CREBH
    Kezhong Zhang; Fiscal Year: 2013
    ..specific transcription factor CREBH (cyclic-AMP-response-element-binding protein H), which is activated by endoplasmic reticulum (ER) stress to mediate an acute-phase inflammatory response in the liver...
  19. Role of Membrane Modifications in the Bioactivities of Conjugated Linoleic Acids
    Papasani V Subbaiah; Fiscal Year: 2013
    ..membrane structure, especially the raft domains of the plasma membrane, and the micro environment of the endoplasmic reticulum (ER)...
  20. Lipid Transport, Bile Acid Synthesis, and Cholesterol Homeostasis
    William M Pandak; Fiscal Year: 2013
    ..in NAFLD appears to produce injury in part by inducing the unfolded protein response (UPR) in the endoplasmic reticulum;a progression of similar events to those found with the development of atherosclerosis...
  21. Regulation of Triglyceride Metabolism by the transcription factor CREB-H
    Ann Hwee Lee; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): CREB-H is an endoplasmic reticulum (ER)-bound transcription factor that is highly and selectively expressed only in the liver and the small intestine...
  22. Imbalances in Calcium Homeostasis: Mechanism Behind Ethanol-Related Dendritic Deg
    Cynthia A Dlugos; Fiscal Year: 2010
    ..regression is coupled with other degenerative changes in dendrites such as dilation of the smooth endoplasmic reticulum (SER), the major calcium storage component of PN dendrites...
  23. Molecular Pathological Mechanism & Potential Therapeutics of Lafora Disease
    YAN NONE LIU; Fiscal Year: 2010
    ..diseases are diverse abnormal aggregates formed inside or outside of affected neuronal cells and endoplasmic reticulum (ER) stress-induced neuronal apoptosis...
  24. The Mucolipin TRP Ion Channels
    Haoxing Xu; Fiscal Year: 2013
    ..Our third aim is to investigate the role of TRPML1 in lysosomal Ca2+ signaling. Like the endoplasmic reticulum (ER), lysosomes are also believed to be the Ca2+ release sites during certain cellular signaling...
  25. Beta Cell Adaptation to Stress in Baboon Pancreas After Partial Pancreatectomy
    FRANCO BATTISTA FOLLI; Fiscal Year: 2010
    ..Particular emphasis will be placed in amyloidogenesis, and endoplasmic reticulum (ER) stress, insulin signaling (insulin receptor substrate-2, IRS-2) and degradation (insulin degrading ..
  26. The Role of H6PDH and 11beta-HSD1 in Type 2 Diabetes and Obesity
    Yanjun Liu; Fiscal Year: 2013
    ..112-HSD1 therefore plays a crucial role in local steroid reactivation. In the endoplasmic reticulum (ER) lumen, hexose-6-phosphate dehydrogenase (H6PDH) converts glucose-6-phosphate (G6P) and NADP to ..
  27. Enhance Production of Functional Recombinant Human Protein C Variant In Mammalian
    Nienwen Chow; Fiscal Year: 2010
    ..The other approach is to knock down endoplasmic reticulum (ER) stress/chaperone protein GRP78 to increase the efficiency of 5A-PC secretion...
  28. Regulation of Hepatic Lipid and Glucose Metabolism by PC-TP/StarD2
    David E Cohen; Fiscal Year: 2013
    ..hepatic insulin resistance due to overproduction of saturated free fatty acids, which in turn promote endoplasmic reticulum (ER) stress...
  29. Eosinophil ORMDL3 and allergic inflammation
    P Sriramarao; Fiscal Year: 2012
    ..demonstrating that ORMDL3 functions as a mediator of sphingolipid homeostasis in yeast and a regulator of endoplasmic reticulum-mediated Ca2+ signaling and cellular stress, very little is known regarding the role played by this ..
  30. MOUSE MODEL FOR DISEASES OF PROTEIN MISFOLDING
    P Michael Conn; Fiscal Year: 2012
    ..proteins are detected by the cellular quality control system (QCS) and are typically retained in the endoplasmic reticulum (ER) for either reprocessing or degradation;frequently, these mutants result in disease...
  31. Effect of HIV protease inhibitor on alcohol induced ER stress and liver injury.
    Cheng Ji; Fiscal Year: 2013
    ..Emerging evidence indicates that the HIV PIs induce endoplasmic reticulum (ER) stress response which has been shown to play an essential role in liver dysfunction including ..
  32. Protein Modifications and Unfolded Protein Response in Diabetic Embryopathy
    Zhiyong Zhao; Fiscal Year: 2013
    ..of chaperone proteins, which facilitate folding and processing of newly synthesized polypeptides in the endoplasmic reticulum (ER) and transporting out of its lumen...
  33. Mechanisms of diet-induced leptin resistance in ARC and VTA
    Philip J Scarpace; Fiscal Year: 2013
    ..We suggest that diets that lead to over-consumption, exacerbated by fructose, promote inflammation, endoplasmic reticulum (ER) stress, and reactive oxygen species (ROS) and these specifically inhibit leptin-mediated STAT3 ..
  34. mTORC1-dependent regulation of the CycC/CDK8 complex
    Jeffrey E Pessin; Fiscal Year: 2013
    ..increasing SREBP-1c transcription;2) protelytic maturation from its precursor that is initially located in endoplasmic reticulum membrane, and 3) increased nuclear SREBP-1c protein stability...
  35. Novel Chaperone Mechanism for Platelet Disorder
    Zihai Li; Fiscal Year: 2010
    ..gp96 (grp94, HSP90b) is a paralogue of HSP90 in the endoplasmic reticulum (ER) where the assembly of GPIb-IX-V complex occurs...
  36. Lipid Metabolism and Steatosis in Liver
    Amrita Kamat; Fiscal Year: 2013
    ..of hepatic lipid metabolism with distinct functions depending on its subcellular localization;in the endoplasmic reticulum (ER) it functions as a triglyceride (TG) synthetic enzyme, whereas in the nucleus it acts as a ..
  37. Thiol Isomerases During Thrombus Formation
    Barbara C Furie; Fiscal Year: 2013
    ..applicant): Thiol isomerases are critical for disulfide bond formation during protein synthesis within the endoplasmic reticulum, but protein thiol isomerases located outside of the endoplasmic reticulum may be critical for regulation ..
  38. Phospholipid flip-flop in biogenic membranes
    Anant K Menon; Fiscal Year: 2013
    ..Lipid flip-flop across the endoplasmic reticulum (ER) membrane is required for protein N-glycosylation and GPI-anchoring...
  39. HEPATIC DEGRADATION OF CYTOCHROME P450 ENZYMES
    Maria Almira Correia; Fiscal Year: 2013
    ....
  40. The Role of FKBP10 in Recessive Osteogenesis Imperfecta
    Caressa Lietman; Fiscal Year: 2013
    ..Shock Protein 47 (HSP47) and together they are thought to be involved in chaperoning of collagen in the endoplasmic reticulum [4, 5]...
  41. Avoiding toxicity associated with MTP ablation
    M Mahmood Hussain; Fiscal Year: 2013
    ..to lower plasma lipids is to inhibit apoB-lipoprotein biosynthesis, a process critically dependent on an endoplasmic reticulum (ER) resident chaperone, microsomal triglyceride transfer protein (MTP)...
  42. Genetically testing interactions of ER and oxidative stresses in retinal disease
    Douglas Gould; Fiscal Year: 2013
    ..Our preliminary data couple the basic cellular processes of endoplasmic reticulum (ER) homeostasis and detoxification of reactive oxygen species to retinal disease...
  43. Smooth muscle cell lipid metabolism and serum amyloid A
    Barbara M Schreiber; Fiscal Year: 2010
    ..that SAA 1) is synthesized by SMCs in response to IL-1ct, 2) induces trafficking of cholesterol to the endoplasmic reticulum (ER), 3) down-regulates cholesterol and fatty acid synthesis and 4) decreases accumulation of cholesterol ..
  44. Role of lipoxygenase pathway in early microvascular dysfunction during diabetic r
    MOHAMED AL SAYED AL-SHABRAWEY; Fiscal Year: 2013
    ..NADPH oxidase and endoplasmic reticulum (ER) are potential targets to the increased lipid metabolites of 12/15-LOX...
  45. Molecular Mechanisms in Bone Resorption
    Steven A Lietman; Fiscal Year: 2013
    ..C (PI-PLC), and the production of inositol phosphate 3 (IP3) leads to release of calcium from the endoplasmic reticulum. The increase in intracellular calcium can activate calcineurin, which dephosphorylates NFATc1 and ..
  46. Atherogenic mechanism of lipid peroxidation-derived aldehydes
    Sanjay Srivastava; Fiscal Year: 2013
    ..studies, we propose to test hypothesis that accumulation of lipid-derived aldehydes in macrophages induces endoplasmic reticulum (ER) stress and triggers the unfolded protein response (UPR), leading to cytokine production and foam cell ..
  47. METABOLIC REGULATION IN THE ACUTE PHASE
    HYUNG D RYOO; Fiscal Year: 2010
    ..The endoplasmic reticulum (ER), which handles the early post-translational processing of secreted proteins tries to maintain a ..
  48. Bacterial Immunosuppression: Host Target Identification Through Chemical Probes
    Kim D Janda; Fiscal Year: 2013
    ..NF-?B-dependent immune system effectors, exposure of mammalian cells to C12 resulted in activation of the endoplasmic reticulum (ER) stress response, protein kinase p38 pathway and apoptosis...
  49. Role of Central Neural NFkB and ER Stress in Obesity-induced Hypertension
    COLIN NEAL YOUNG; Fiscal Year: 2013
    ..In this regard, there is mounting evidence that angiotensinergic signaling and endoplasmic reticulum stress (ER stress) within the brain are key mechanisms in diet-induced obesity (DIO);however the ..
  50. Redox Regulation of SERCA by Nitric Oxide
    Richard A Cohen; Fiscal Year: 2013
    ..The studies funded by this proposal have identified the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) to be stimulated by 7NO via its ability to introduce glutathione SERCA adducts, ..
  51. CFTR Biogenesis and Function in Epithelia
    Zsuzsa Bebok; Fiscal Year: 2012
    ..selectively represses the transcription of genes through a promoter-specific mechanism;2) the UPR enhances endoplasmic reticulum-associated degradation (ERAD) by decreasing the expression of pro-folding chaperones and enhancing the ..
  52. Selenoprotein K modulates calcium-dependent signaling in immune cells
    PETER R HOFFMAN; Fiscal Year: 2013
    ..Our preliminary data indicate Sel K protein expression is highest in immune cells, localizing to the endoplasmic reticulum (ER) membrane in T cells, monocytes, and macrophages...
  53. N-Glycosylation And ER Stress
    MARK LEHRMAN; Fiscal Year: 2012
    ..cell surface (including cell adhesion molecules and signaling receptors) are produced and folded by the endoplasmic reticulum (ER). If the ER has problems folding these proteins, a compensatory "ER stress response" (a.k.a...
  54. Identification of Inhibitors that Stabilize ER Degradation Substrates
    Domenico Tortorella; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Newly synthesized endoplasmic reticulum (ER) proteins are subjected to inspection by the ER quality control machinery to ensure that only properly folded molecules can traffic to their final ..
  55. Characterizaton of Motility Factor Receptor
    Avraham Raz; Fiscal Year: 2012
    ..is an orphan chemokine receptor, (gp78/AMFR/CXC2CR-1) that performs an additional function in the endoplasmic reticulum (ER) with an intrinsic RING finger-dependent ubiquitin protein ligase (E3) activity...
  56. Mechanisms of ER stress - induced fatty liver
    D Thomas Rutkowski; Fiscal Year: 2013
    ..This research proposal is based upon strong preliminary data demonstrating that endoplasmic reticulum (ER) stress leads to transcriptional suppression of genes involved in maintaining lipid homeostasis;mice ..
  57. The Unfolded Protein Response in Human Airway and Alveolar Epithelial Cells
    Salim Merali; Fiscal Year: 2010
    ..We have shown that the lungs of chronic cigarette smokers without COPD manifest a compensatory response to endoplasmic reticulum stress termed the unfolded protein response (UPR) and that the UPR-related transcription factors, ATF-4 ..
  58. Retroviral Subversion of ERAD and Intrinsic Immunity
    JAQUELIN PAGE DUDLEY; Fiscal Year: 2013
    ..Transmembrane and secreted proteins use a signal peptide (SP) to direct translation to the endoplasmic reticulum (ER), where an error-prone process of protein folding and modification occur...
  59. Mechanisms of Cell Death after Photodynamic Therapy
    Anna Liisa Nieminen; Fiscal Year: 2010
    ..However, PC 4 and a recently synthesized PC 4 derivative PC 181 also localize to endoplasmic reticulum (ER) and lysosomes...
  60. Heat shock protein 90 antagonist-based therapy of mantle cell lymphoma
    Kapil Bhalla; Fiscal Year: 2012
    ..Additionally, GAA treatment depleted the mediators of endoplasmic reticulum (ER) stress PKR and IRE-11...
  61. GABA chaperoning of epilepsy-associated GABAA receptor mutants.
    Nancy J Leidenheimer; Fiscal Year: 2012
    ..2010). Some of these mutants are retained in the endoplasmic reticulum (ER) due to inefficient folding and processing, resulting in deficits in cell surface expression...
  62. The role of two-pore channels in integrative calcium signaling
    Michael X Zhu; Fiscal Year: 2013
    ..Furthermore, the NAADP-elicited Ca2+ signal is coupled to Ca2+ release from the endoplasmic reticulum, suggesting a cross-talk between NAADP and IP3 receptors...
  63. Coordination of Pathophysiologic Endothelial Cell Signaling by ROS
    Madesh Muniswamy; Fiscal Year: 2012
    ..In this proposal, we postulate that superoxide is a signaling molecule that facilitates endoplasmic reticulum Ca2+ signaling and triggers mitochondrial and nuclear stress...
  64. Alteration of ER:mitochondrial contacts by human cytomegalovirus infection
    ANAMARIS MARTHA COLBERG POLEY; Fiscal Year: 2010
    ..Following synthesis, UL37 proteins are translocated into the endoplasmic reticulum (ER) membrane and then imported into mitochondria, where they have potent anti- apoptotic functions...
  65. Simian Virus 40 (SV40) uncoating and penetration
    Daniel Hebert; Fiscal Year: 2009
    ..Some viruses, including SV40 are transported to the endoplasmic reticulum (ER)...
  66. ISOLATION OF ELONGATION ENZYMES & SITE OF SYNTHESIS
    DOMINICK CINTI; Fiscal Year: 1991
    ..of each of the enzymatic components of the fatty acid chain elongation system present in the hepatic endoplasmic reticulum. Having recently purified, to apparent homogeneity, two of the components, namely, NADPH-specific trans-2-..
  67. MOLECULAR PHYSIOLOGY OF BILIARY LIPID SECRETION
    David Cohen; Fiscal Year: 2000
    ..salts in submicellar concentrations promote transfer of biliary phosphatidylcholine molecules from smooth endoplasmic reticulum to canalicular plasma membranes via a specific phosphatidylcholine transfer protein (PC-TP)...
  68. Endoplasmic reticulum stress and foam cell formation
    Zhongmao Guo; Fiscal Year: 2010
    ..The goal of this proposal is to determine the involvement of endoplasmic reticulum stress in foam cell formation...
  69. SIGNAL PEPTIDASE STRUCTURE AND FUNCTION
    MARK LIVELY; Fiscal Year: 1999
    ..proteolytic enzyme that cleaves signal peptides from secretory proteins targeted to the lumen of the endoplasmic reticulum. The enzyme activity is associated with a complex of from two to five integral membrane proteins with ..
  70. SURFACE MEMBRANES IN NORMAL AND CANCER CELLS
    Paul Atkinson; Fiscal Year: 1991
    Cloned endoplasmic reticulum membrane glycoprotein genes will be used to probe the primary sequence requirements directing the sorting of glycoproteins into specific membrane compartments...
  71. ENDOPLASMIC RETICULUM IN SEA URCHIN EGG
    BENJAMIN KAMINER; Fiscal Year: 1990
    Our long-term objective is to gain an understanding of the role of the smooth endoplasmic reticulum (SER) a regulator of extracellular calcium, which acts as a messenger and modulator of numerous events following fertilization of the egg...
  72. From Unfolded Proteins in the ER to Disease
    Linda Hendershot; Fiscal Year: 2009
    ..cells, proteins destined for the cell surface or for the external milieu are first translocated into the endoplasmic reticulum (ER) where initial protein folding and modifications occur that are essential for the protein to attain ..
  73. Effects--Ethanol--Dendritic Smooth Endoplasmic Reticulum
    Cynthia Dlugos; Fiscal Year: 2003
    ..periods of ethanol consumption result in dendritic regression and dilatation of the dendritic smooth endoplasmic reticulum (SER) within the extensive dendritic arbor of PN...
  74. Screening for Inhibitors of the Integrated Stress Response
    David Ron; Fiscal Year: 2007
    ..such as hormones, enzymes and cell surface receptors undergo early steps of their biogenesis in the endoplasmic reticulum (ER)...
  75. PROTEIN QUALITY CONTROL IN THE ENDOPLASMIC RETICULUM
    KARL WITTRUP; Fiscal Year: 2001
    DESCRIPTION: [From the applicant's abstract]: Misfolded and unassembled proteins are retained in the endoplasmic reticulum via a process termed "quality control," ensuring that only native proteins are secreted to the extracellular ..
  76. ENDOMEMBRANE TRAFFICKING OF FIV ENVELOPE GLYCOPROTEINS
    D Morre; Fiscal Year: 1993
    This proposal is to characterize the endomembrane trafficking between transitional endoplasmic reticulum and cis Golgi apparatus in lentivirus coat protein processing as a strategy for target identification in antiviral drug design using ..