Home LiteratureArticle Details
PMID: 12438434 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S. Review

Orchestrating the unfolded protein response in health and disease.

The Journal of clinical investigation ·Vol. 110 ·No. 10 ·2002-11-00 ·Pages 1389-98

Kaufman RJ

Abstract

暂无摘要

MeSH Terms
Activating Transcription Factor 6 Apoptosis DNA-Binding Proteins/metabolism Diabetes Mellitus/genetics,metabolism Endoplasmic Reticulum/metabolism Endoribonucleases Enzyme Activation Genetic Diseases, Inborn/genetics,metabolism Glucose/metabolism Humans Hyperhomocysteinemia/genetics,metabolism Ischemia/metabolism Membrane Proteins Models, Biological Neoplasms/genetics,metabolism Organelles/metabolism Protein Folding Protein Serine-Threonine Kinases/genetics,metabolism RNA Splicing Signal Transduction Stress, Physiological/genetics,metabolism Transcription Factors/metabolism Virus Diseases/etiology,metabolism eIF-2 Kinase/metabolism
Chemicals
ATF6 protein, human Activating Transcription Factor 6 DNA-Binding Proteins Membrane Proteins Transcription Factors ERN2 protein, human PERK kinase Protein Serine-Threonine Kinases eIF-2 Kinase Endoribonucleases Glucose
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Kaufman Randal J
Department of Biological Chemistry, Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor 48109-0650, USA. kaufmanr@umich.edu
References (87)
87 references, click to expand
  1. Complementary signaling pathways regulate the unfolded protein response and are required for C. elegans development.
    Cell. 2001 Dec 28;107(7):893-903 PMID: 11779465
  2. Regulated translation initiation controls stress-induced gene expression in mammalian cells.
    Mol Cell. 2000 Nov;6(5):1099-108 PMID: 11106749
  3. Ultrastructural changes during the enhancement of cellular 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase in a Chinese hamster cell mutant resistant to compactin (ML 236B).
    Cell Struct Funct. 1983 Sep;8(3):309-12 PMID: 6671218
  4. Mammalian stress response: induction of the glucose-regulated protein family.
    Curr Opin Cell Biol. 1992 Apr;4(2):267-73 PMID: 1599691
  5. A lag in intracellular degradation of mutant alpha 1-antitrypsin correlates with the liver disease phenotype in homozygous PiZZ alpha 1-antitrypsin deficiency.
    Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):9014-8 PMID: 8090762
  6. The basic domain/leucine zipper protein hXBP-1 preferentially binds to and transactivates CRE-like sequences containing an ACGT core.
    Nucleic Acids Res. 1996 May 15;24(10):1855-64 PMID: 8657566
  7. Induction of glucose-regulated protein (glucose-regulated protein 78/BiP and glucose-regulated protein 94) and heat shock protein 70 transcripts in the immature rat brain following status epilepticus.
    Neuroscience. 1996 Nov;75(1):209-19 PMID: 8923535
  8. Inducible membranes in yeast: relation to the unfolded-protein-response pathway.
    Yeast. 1997 Oct;13(13):1211-29 PMID: 9364746
  9. Overexpression of Pex15p, a phosphorylated peroxisomal integral membrane protein required for peroxisome assembly in S.cerevisiae, causes proliferation of the endoplasmic reticulum membrane.
    EMBO J. 1997 Dec 15;16(24):7326-41 PMID: 9405362
  10. Genetic tailoring of N-linked oligosaccharides: the role of glucose residues in glycoprotein processing of Saccharomyces cerevisiae in vivo.
    Glycobiology. 1998 Feb;8(2):155-64 PMID: 9451025
  11. Involvement of endoplasmic reticulum chaperones in the folding of hepatitis C virus glycoproteins.
    J Virol. 1998 May;72(5):3851-8 PMID: 9557669
  12. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism.
    Nature. 1998 Apr 9;392(6676):605-8 PMID: 9560156
  13. A stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells.
    Genes Dev. 1998 Jun 15;12(12):1812-24 PMID: 9637683
  14. Cloning of mammalian Ire1 reveals diversity in the ER stress responses.
    EMBO J. 1998 Oct 1;17(19):5708-17 PMID: 9755171
  15. Identification of the cis-acting endoplasmic reticulum stress response element responsible for transcriptional induction of mammalian glucose-regulated proteins. Involvement of basic leucine zipper transcription factors.
    J Biol Chem. 1998 Dec 11;273(50):33741-9 PMID: 9837962
  16. Molecular mechanisms and regulation of insulin exocytosis as a paradigm of endocrine secretion.
    Eur J Biochem. 1999 Jan;259(1-2):3-17 PMID: 9914469
  17. Null mutation in IRE1 gene inhibits overproduction of microsomal cytochrome P450Alk1 (CYP 52A3) and proliferation of the endoplasmic reticulum in Saccharomyces cerevisiae.
    J Biochem. 1999 Mar;125(3):507-14 PMID: 10050038
  18. Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls.
    Genes Dev. 1999 May 15;13(10):1211-33 PMID: 10346810
  19. Homocysteine-induced endoplasmic reticulum stress and growth arrest leads to specific changes in gene expression in human vascular endothelial cells.
    Blood. 1999 Aug 1;94(3):959-67 PMID: 10419887
  20. Targeted disruption of CRE-binding factor TREB5 gene leads to cellular necrosis in cardiac myocytes at the embryonic stage.
    Biochem Biophys Res Commun. 1999 Aug 2;261(2):350-6 PMID: 10425189
  21. Cellular origin of hexokinase in pancreatic islets.
    J Biol Chem. 1999 Nov 12;274(46):32803-9 PMID: 10551841
  22. Diverse functions of JNK signaling and c-Jun in stress response and apoptosis.
    Oncogene. 1999 Nov 1;18(45):6158-62 PMID: 10557107
  23. Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress.
    Mol Biol Cell. 1999 Nov;10(11):3787-99 PMID: 10564271
  24. Procollagen folding and assembly: the role of endoplasmic reticulum enzymes and molecular chaperones.
    Semin Cell Dev Biol. 1999 Oct;10(5):455-64 PMID: 10597628
  25. A role for presenilin-1 in nuclear accumulation of Ire1 fragments and induction of the mammalian unfolded protein response.
    Cell. 1999 Dec 23;99(7):691-702 PMID: 10619423
  26. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta.
    Nature. 2000 Jan 6;403(6765):98-103 PMID: 10638761
  27. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1.
    Science. 2000 Jan 28;287(5453):664-6 PMID: 10650002
  28. An essential role in liver development for transcription factor XBP-1.
    Genes Dev. 2000 Jan 15;14(2):152-7 PMID: 10652269
  29. mRNA splicing-mediated C-terminal replacement of transcription factor Hac1p is required for efficient activation of the unfolded protein response.
    Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4660-5 PMID: 10781071
  30. Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation.
    Cell. 2000 Apr 28;101(3):249-58 PMID: 10847680
  31. Tripartite management of unfolded proteins in the endoplasmic reticulum.
    Cell. 2000 May 26;101(5):451-4 PMID: 10850487
  32. ATF6 as a transcription activator of the endoplasmic reticulum stress element: thapsigargin stress-induced changes and synergistic interactions with NF-Y and YY1.
    Mol Cell Biol. 2000 Jul;20(14):5096-106 PMID: 10866666
  33. Ligand-independent dimerization activates the stress response kinases IRE1 and PERK in the lumen of the endoplasmic reticulum.
    J Biol Chem. 2000 Aug 11;275(32):24881-5 PMID: 10835430
  34. EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome.
    Nat Genet. 2000 Aug;25(4):406-9 PMID: 10932183
  35. Cross-talk between two cysteine protease families. Activation of caspase-12 by calpain in apoptosis.
    J Cell Biol. 2000 Aug 21;150(4):887-94 PMID: 10953012
  36. ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response.
    Mol Cell Biol. 2000 Sep;20(18):6755-67 PMID: 10958673
  37. Activation of ATF6 and an ATF6 DNA binding site by the endoplasmic reticulum stress response.
    J Biol Chem. 2000 Sep 1;275(35):27013-20 PMID: 10856300
  38. Regulated step in cholesterol feedback localized to budding of SCAP from ER membranes.
    Cell. 2000 Aug 4;102(3):315-23 PMID: 10975522
  39. IRE1 and efferent signaling from the endoplasmic reticulum.
    J Cell Sci. 2000 Nov;113 Pt 21:3697-702 PMID: 11034898
  40. The endoribonuclease activity of mammalian IRE1 autoregulates its mRNA and is required for the unfolded protein response.
    Genes Dev. 2000 Nov 1;14(21):2725-36 PMID: 11069889
  41. Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity.
    J Biol Chem. 2000 Nov 17;275(46):35661-4 PMID: 10973942
  42. Endoplasmic reticulum stress-induced formation of transcription factor complex ERSF including NF-Y (CBF) and activating transcription factors 6alpha and 6beta that activates the mammalian unfolded protein response.
    Mol Cell Biol. 2001 Feb;21(4):1239-48 PMID: 11158310
  43. ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs.
    Mol Cell. 2000 Dec;6(6):1355-64 PMID: 11163209
  44. Increased sensitivity to dextran sodium sulfate colitis in IRE1beta-deficient mice.
    J Clin Invest. 2001 Mar;107(5):585-93 PMID: 11238559
  45. Identification of ERSE-II, a new cis-acting element responsible for the ATF6-dependent mammalian unfolded protein response.
    J Biol Chem. 2001 Mar 23;276(12):9199-205 PMID: 11112790
  46. Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model.
    J Clin Invest. 2001 Mar;107(6):675-83 PMID: 11254667
  47. Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress.
    J Biol Chem. 2001 Apr 27;276(17):13935-40 PMID: 11278723
  48. Intracellular signaling from the endoplasmic reticulum to the nucleus: the unfolded protein response in yeast and mammals.
    Curr Opin Cell Biol. 2001 Jun;13(3):349-55 PMID: 11343907
  49. Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways.
    J Clin Invest. 2001 May;107(10):1263-73 PMID: 11375416
  50. Impairment of the ubiquitin-proteasome system by protein aggregation.
    Science. 2001 May 25;292(5521):1552-5 PMID: 11375494
  51. The Ca2+ concentration of the endoplasmic reticulum is a key determinant of ceramide-induced apoptosis: significance for the molecular mechanism of Bcl-2 action.
    EMBO J. 2001 Jun 1;20(11):2690-701 PMID: 11387204
  52. Brain ischemia and reperfusion activates the eukaryotic initiation factor 2alpha kinase, PERK.
    J Neurochem. 2001 Jun;77(5):1418-21 PMID: 11389192
  53. Diabetes mellitus and exocrine pancreatic dysfunction in perk-/- mice reveals a role for translational control in secretory cell survival.
    Mol Cell. 2001 Jun;7(6):1153-63 PMID: 11430819
  54. Translational control is required for the unfolded protein response and in vivo glucose homeostasis.
    Mol Cell. 2001 Jun;7(6):1165-76 PMID: 11430820
  55. Homocysteine thiolactone induces apoptotic DNA damage mediated by increased intracellular hydrogen peroxide and caspase 3 activation in HL-60 cells.
    Life Sci. 2001 May 11;68(25):2799-811 PMID: 11432446
  56. An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin.
    Cell. 2001 Jun 29;105(7):891-902 PMID: 11439185
  57. ER quality control: towards an understanding at the molecular level.
    Curr Opin Cell Biol. 2001 Aug;13(4):431-7 PMID: 11454449
  58. Plasma cell differentiation requires the transcription factor XBP-1.
    Nature. 2001 Jul 19;412(6844):300-7 PMID: 11460154
  59. The glucose-regulated proteins: stress induction and clinical applications.
    Trends Biochem Sci. 2001 Aug;26(8):504-10 PMID: 11504627
  60. Targeting of the c-Abl tyrosine kinase to mitochondria in endoplasmic reticulum stress-induced apoptosis.
    Mol Cell Biol. 2001 Sep;21(18):6233-42 PMID: 11509666
  61. Coupling endoplasmic reticulum stress to the cell death program. Mechanism of caspase activation.
    J Biol Chem. 2001 Sep 7;276(36):33869-74 PMID: 11448953
  62. Dietary supplementation with methionine and homocysteine promotes early atherosclerosis but not plaque rupture in ApoE-deficient mice.
    Arterioscler Thromb Vasc Biol. 2001 Sep;21(9):1470-6 PMID: 11557674
  63. Homocysteine induces programmed cell death in human vascular endothelial cells through activation of the unfolded protein response.
    J Biol Chem. 2001 Sep 21;276(38):35867-74 PMID: 11447214
  64. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor.
    Cell. 2001 Dec 28;107(7):881-91 PMID: 11779464
  65. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA.
    Nature. 2002 Jan 3;415(6867):92-6 PMID: 11780124
  66. Molecular pathways of protein synthesis inhibition during brain reperfusion: implications for neuronal survival or death.
    J Cereb Blood Flow Metab. 2002 Feb;22(2):127-41 PMID: 11823711
  67. IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response.
    Genes Dev. 2002 Feb 15;16(4):452-66 PMID: 11850408
  68. Targeted disruption of the Chop gene delays endoplasmic reticulum stress-mediated diabetes.
    J Clin Invest. 2002 Feb;109(4):525-32 PMID: 11854325
  69. Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer's disease.
    J Neurosci. 2002 Mar 1;22(5):1752-62 PMID: 11880504
  70. Induction of secretory pathway components in yeast is associated with increased stability of their mRNA.
    J Cell Biol. 2002 Mar 18;156(6):993-1001 PMID: 11901166
  71. Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid beta-protein.
    J Biol Chem. 2002 Apr 12;277(15):12915-20 PMID: 11799129
  72. The PERK eukaryotic initiation factor 2 alpha kinase is required for the development of the skeletal system, postnatal growth, and the function and viability of the pancreas.
    Mol Cell Biol. 2002 Jun;22(11):3864-74 PMID: 11997520
  73. The protein kinase/endoribonuclease IRE1alpha that signals the unfolded protein response has a luminal N-terminal ligand-independent dimerization domain.
    J Biol Chem. 2002 May 24;277(21):18346-56 PMID: 11897784
  74. The unfolded protein response in nutrient sensing and differentiation.
    Nat Rev Mol Cell Biol. 2002 Jun;3(6):411-21 PMID: 12042763
  75. ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats.
    Genes Dev. 2002 Jun 1;16(11):1345-55 PMID: 12050113
  76. Coupling endoplasmic reticulum stress to the cell death program. An Apaf-1-independent intrinsic pathway.
    J Biol Chem. 2002 Jun 14;277(24):21836-42 PMID: 11919205
  77. ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals.
    Dev Cell. 2002 Jul;3(1):99-111 PMID: 12110171
  78. Preclinical and clinical evaluation of proteasome inhibitor PS-341 for the treatment of cancer.
    Curr Opin Chem Biol. 2002 Aug;6(4):493-500 PMID: 12133726
  79. CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity.
    Mol Cell. 2002 Jul;10(1):55-67 PMID: 12150907
  80. An endoplasmic reticulum stress-specific caspase cascade in apoptosis. Cytochrome c-independent activation of caspase-9 by caspase-12.
    J Biol Chem. 2002 Sep 13;277(37):34287-94 PMID: 12097332
  81. Protein aggregation in disease: a role for folding intermediates forming specific multimeric interactions.
    J Clin Invest. 2002 Nov;110(9):1221-32 PMID: 12417558
  82. Translational control in the endoplasmic reticulum stress response.
    J Clin Invest. 2002 Nov;110(10):1383-8 PMID: 12438433
  83. Alpha1-antitrypsin polymerization and the serpinopathies: pathobiology and prospects for therapy.
    J Clin Invest. 2002 Dec;110(11):1585-90 PMID: 12464660
  84. Rescuing protein conformation: prospects for pharmacological therapy in cystic fibrosis.
    J Clin Invest. 2002 Dec;110(11):1591-7 PMID: 12464661
  85. Chaperoning brain degeneration.
    Proc Natl Acad Sci U S A. 2002 Dec 10;99 Suppl 4:16407-11 PMID: 12149445
  86. Effect of glucose on initiation and elongation rates in isolated rat pancreatic islets.
    J Biol Chem. 1974 May 10;249(9):2738-42 PMID: 4597460
  87. Translational control of proinsulin synthesis by glucose.
    Nature. 1980 Jan 3;283(5742):100-2 PMID: 6985712
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI16886
Email
kaufmanr@umich.edu
Published
2002-11-00
Pages
1389-98
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC151822
Subset
IM
Grants
NIAID NIH HHS · AI-42394 · United States
External Links
PubMed source DOI: 10.1172/JCI16886 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2