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PMID: 12380691 Published · ppublish English Journal Article Review

The mammalian endoplasmic reticulum as a sensor for cellular stress.

Cell stress & chaperones ·Vol. 7 ·No. 2 ·2002-04-00 ·Pages 222-9

Ma Y, Hendershot LM

Abstract

The recent elucidation of the mammalian unfolded protein response pathway has revealed a unique and transcriptionally complex signal transduction pathway that protects cells from a variety of physical and biochemical stresses that can occur during normal development and in disease states. Although the stress conditions are monitored in the endoplasmic reticulum, the beneficial effects of this pathway are extended to other cellular organelles and to the organism itself.

MeSH Terms
Animals Cell Survival/physiology Endoplasmic Reticulum/chemistry,physiology Environmental Exposure Mice Molecular Chaperones/chemistry,physiology Protein Folding Signal Transduction/physiology Stress, Mechanical
Chemicals
Molecular Chaperones
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Ma Yanjun
Department of Tumor Cell Biology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Hendershot Linda M
References (80)
80 references, click to expand
  1. A transmembrane protein with a cdc2+/CDC28-related kinase activity is required for signaling from the ER to the nucleus.
    Cell. 1993 Aug 27;74(4):743-56 PMID: 8358794
  2. Increased cytotoxicity of chronic hypoxic cells by molecular inhibition of GRP78 induction.
    Int J Radiat Oncol Biol Phys. 1994 Feb 1;28(3):661-6 PMID: 8113109
  3. Molecular and cellular physiology of intracellular calcium stores.
    Physiol Rev. 1994 Jul;74(3):595-636 PMID: 8036248
  4. The differential effects of dithiothreitol and 2-mercaptoethanol on the secretion of partially and completely assembled immunoglobulins suggest that thiol-mediated retention does not take place in or beyond the Golgi.
    Mol Biol Cell. 1994 Dec;5(12):1311-24 PMID: 7696712
  5. Regulation of protein synthesis by heme-regulated eIF-2 alpha kinase.
    Trends Biochem Sci. 1995 Mar;20(3):105-8 PMID: 7709427
  6. A novel signal transduction pathway from the endoplasmic reticulum to the nucleus is mediated by transcription factor NF-kappa B.
    EMBO J. 1995 Jun 1;14(11):2580-8 PMID: 7781611
  7. A mechanism for the specific immunogenicity of heat shock protein-chaperoned peptides.
    Science. 1995 Sep 15;269(5230):1585-8 PMID: 7545313
  8. Up-regulation of heat shock protein 70 in adenocarcinomas of the lung in smokers.
    Anticancer Res. 1995 Nov-Dec;15(6B):2607-9 PMID: 8669833
  9. Inhibition of tumor progression by suppression of stress protein GRP78/BiP induction in fibrosarcoma B/C10ME.
    Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7690-4 PMID: 8755537
  10. Inhibition of translational initiation by activators of the glucose-regulated stress protein and heat shock protein stress response systems. Role of the interferon-inducible double-stranded RNA-activated eukaryotic initiation factor 2alpha kinase.
    J Biol Chem. 1996 Oct 4;271(40):24995-5002 PMID: 8798781
  11. A novel mechanism for regulating activity of a transcription factor that controls the unfolded protein response.
    Cell. 1996 Nov 1;87(3):391-404 PMID: 8898193
  12. Interaction of endoplasmic reticulum chaperone GRP94 with peptide substrates is adenine nucleotide-independent.
    J Biol Chem. 1997 Feb 21;272(8):5152-6 PMID: 9030582
  13. The transmembrane kinase Ire1p is a site-specific endonuclease that initiates mRNA splicing in the unfolded protein response.
    Cell. 1997 Sep 19;90(6):1031-9 PMID: 9323131
  14. Priming of T cells by heat shock protein-peptide complexes as the basis of tumor vaccines.
    Semin Immunol. 1997 Oct;9(5):315-22 PMID: 9327526
  15. Hypersensitivity to DNA cross-linking agents associated with up-regulation of glucose-regulated stress protein GRP78.
    Cancer Res. 1997 Nov 15;57(22):5112-6 PMID: 9371511
  16. CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum.
    Genes Dev. 1998 Apr 1;12(7):982-95 PMID: 9531536
  17. 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
  18. Cloning of mammalian Ire1 reveals diversity in the ER stress responses.
    EMBO J. 1998 Oct 1;17(19):5708-17 PMID: 9755171
  19. Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control.
    Mol Cell Biol. 1998 Dec;18(12):7499-509 PMID: 9819435
  20. 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
  21. The requirement for molecular chaperones during endoplasmic reticulum-associated protein degradation demonstrates that protein export and import are mechanistically distinct.
    J Biol Chem. 1999 Feb 5;274(6):3453-60 PMID: 9920890
  22. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase.
    Nature. 1999 Jan 21;397(6716):271-4 PMID: 9930704
  23. Escaping cell death: survival proteins in cancer.
    Exp Cell Res. 1999 Apr 10;248(1):30-43 PMID: 10094811
  24. Mammalian unfolded protein response inhibits cyclin D1 translation and cell-cycle progression.
    Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8505-10 PMID: 10411905
  25. Overexpression of GRP78 mitigates stress induction of glucose regulated proteins and blocks secretion of selective proteins in Chinese hamster ovary cells.
    EMBO J. 1992 Apr;11(4):1563-71 PMID: 1373378
  26. Interaction of BiP with newly synthesized immunoglobulin light chain molecules: cycles of sequential binding and release.
    EMBO J. 1992 Apr;11(4):1573-81 PMID: 1563355
  27. Intracellular calcium: molecules and pools.
    Curr Opin Cell Biol. 1992 Apr;4(2):220-6 PMID: 1318061
  28. PKR; a sentinel kinase for cellular stress.
    Oncogene. 1999 Nov 1;18(45):6112-20 PMID: 10557102
  29. 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
  30. Setting the standards: quality control in the secretory pathway.
    Science. 1999 Dec 3;286(5446):1882-8 PMID: 10583943
  31. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta.
    Nature. 2000 Jan 6;403(6765):98-103 PMID: 10638761
  32. 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
  33. An essential role in liver development for transcription factor XBP-1.
    Genes Dev. 2000 Jan 15;14(2):152-7 PMID: 10652269
  34. Overexpression of the heat shock protein HSP70 family and p53 protein and prognosis for patients with gastric cancer.
    Oncology. 2000 Feb;58(2):144-51 PMID: 10705241
  35. Overexpression of the glucose-regulated stress gene GRP78 in malignant but not benign human breast lesions.
    Breast Cancer Res Treat. 2000 Jan;59(1):15-26 PMID: 10752676
  36. Stress protein GRP78 prevents apoptosis induced by calcium ionophore, ionomycin, but not by glycosylation inhibitor, tunicamycin, in human prostate cancer cells.
    J Cell Biochem. 2000 Apr;77(3):396-408 PMID: 10760948
  37. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response.
    Nat Cell Biol. 2000 Jun;2(6):326-32 PMID: 10854322
  38. Degradation of proteins from the ER of S. cerevisiae requires an intact unfolded protein response pathway.
    Mol Cell. 2000 Apr;5(4):729-35 PMID: 10882108
  39. A regulatory link between ER-associated protein degradation and the unfolded-protein response.
    Nat Cell Biol. 2000 Jul;2(7):379-84 PMID: 10878801
  40. The sarco/endoplasmic reticulum calcium-ATPase 2b is an endoplasmic reticulum stress-inducible protein.
    J Biol Chem. 2000 Jul 21;275(29):22363-72 PMID: 10748035
  41. 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
  42. Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome.
    Nat Cell Biol. 2000 Aug;2(8):469-75 PMID: 10934466
  43. Negative regulation of the Apaf-1 apoptosome by Hsp70.
    Nat Cell Biol. 2000 Aug;2(8):476-83 PMID: 10934467
  44. Changes in endoplasmic reticulum luminal environment affect cell sensitivity to apoptosis.
    J Cell Biol. 2000 Aug 21;150(4):731-40 PMID: 10952999
  45. 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
  46. Hsp27 negatively regulates cell death by interacting with cytochrome c.
    Nat Cell Biol. 2000 Sep;2(9):645-52 PMID: 10980706
  47. Heat-shock proteins as death determinants.
    Nat Cell Biol. 2000 Sep;2(9):E163-5 PMID: 10980714
  48. Dissociation of Kar2p/BiP from an ER sensory molecule, Ire1p, triggers the unfolded protein response in yeast.
    Biochem Biophys Res Commun. 2000 Dec 20;279(2):445-50 PMID: 11118306
  49. Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state.
    Mol Cell Biol. 2001 Feb;21(4):1249-59 PMID: 11158311
  50. 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
  51. ORP150 protects against hypoxia/ischemia-induced neuronal death.
    Nat Med. 2001 Mar;7(3):317-23 PMID: 11231630
  52. 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
  53. Regulation of tumor angiogenesis by oxygen-regulated protein 150, an inducible endoplasmic reticulum chaperone.
    Cancer Res. 2001 May 15;61(10):4206-13 PMID: 11358846
  54. Heat shock protein 27 was up-regulated in cisplatin resistant human ovarian tumor cell line and associated with the cisplatin resistance.
    Cancer Lett. 2001 Jul 26;168(2):173-81 PMID: 11403922
  55. 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
  56. Translational control is required for the unfolded protein response and in vivo glucose homeostasis.
    Mol Cell. 2001 Jun;7(6):1165-76 PMID: 11430820
  57. Expression of the oxygen-regulated protein ORP150 accelerates wound healing by modulating intracellular VEGF transport.
    J Clin Invest. 2001 Jul;108(1):41-50 PMID: 11435456
  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. The expanding role of mitochondria in apoptosis.
    Genes Dev. 2001 Nov 15;15(22):2922-33 PMID: 11711427
  61. Endoplasmic reticulum dysfunction--a common denominator for cell injury in acute and degenerative diseases of the brain?
    J Neurochem. 2001 Nov;79(4):719-25 PMID: 11723164
  62. 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
  63. 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
  64. Regulated translation initiation controls stress-induced gene expression in mammalian cells.
    Mol Cell. 2000 Nov;6(5):1099-108 PMID: 11106749
  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. Regulation of internal ribosome entry site-mediated translation by eukaryotic initiation factor-2alpha phosphorylation and translation of a small upstream open reading frame.
    J Biol Chem. 2002 Jan 18;277(3):2050-8 PMID: 11684693
  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. Two distinct stress signaling pathways converge upon the CHOP promoter during the mammalian unfolded protein response.
    J Mol Biol. 2002 May 17;318(5):1351-65 PMID: 12083523
  69. Isolation and cell cycle analysis of temperature-sensitive mutants from Chinese hamster cells.
    J Cell Physiol. 1979 Jan;98(1):17-30 PMID: 762193
  70. Generation of a mutant form of protein synthesis initiation factor eIF-2 lacking the site of phosphorylation by eIF-2 kinases.
    Mol Cell Biol. 1988 Feb;8(2):993-5 PMID: 3352609
  71. The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins.
    Nature. 1988 Mar 31;332(6163):462-4 PMID: 3352747
  72. The involvement of calcium in transport of secretory proteins from the endoplasmic reticulum.
    Cell. 1990 Apr 20;61(2):197-9 PMID: 2184940
  73. Flux of the paramyxovirus hemagglutinin-neuraminidase glycoprotein through the endoplasmic reticulum activates transcription of the GRP78-BiP gene.
    J Virol. 1991 Jul;65(7):3590-7 PMID: 2041085
  74. Protein folding in the cell.
    Nature. 1992 Jan 2;355(6355):33-45 PMID: 1731198
  75. A 22 bp cis-acting element is necessary and sufficient for the induction of the yeast KAR2 (BiP) gene by unfolded proteins.
    EMBO J. 1992 Jul;11(7):2583-93 PMID: 1628622
  76. Phosphorylation of eukaryotic initiation factor (eIF) 2 alpha and inhibition of eIF-2B in GH3 pituitary cells by perturbants of early protein processing that induce GRP78.
    J Biol Chem. 1992 Aug 25;267(24):16751-4 PMID: 1512215
  77. Induction of glucose regulated proteins during growth of a murine tumor.
    J Cell Physiol. 1993 Feb;154(2):229-37 PMID: 8425905
  78. Role of N-linked glycosylation in cell-cycle progression and initiation of DNA synthesis in tumor-transformed human fibroblasts.
    Anticancer Res. 1993 Jan-Feb;13(1):167-71 PMID: 8476209
  79. Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase.
    Cell. 1993 Jun 18;73(6):1197-206 PMID: 8513503
  80. Tumor rejection antigen gp96/grp94 is an ATPase: implications for protein folding and antigen presentation.
    EMBO J. 1993 Aug;12(8):3143-51 PMID: 8344253
Article Info
Journal
Cell stress & chaperones
Abbr.
Cell Stress Chaperones
ISSN
1355-8145
DOI
10.1379/1466-1268(2002)007<0222:tmeraa>2.0.co;2
Published
2002-04-00
Pages
222-9
Language
English
Region
Netherlands
NLM ID
9610925
PMCID
PMC514821
Subset
IM
External Links
PubMed source DOI: 10.1379/1466-1268(2002)007<0222:tmeraa>2.0.co;2 PMC Full Text View journal details
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