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J Clin Invest. Jan 1995; 95(1): 3–12.
PMCID: PMC295356

Clinical implications of the stress response.


A field of research that began with a curious observation in Drosophila has resulted in a new understanding of how cells respond to sudden and adverse changes in their environment. In addition through the study of the structure/function of the stress proteins, especially those which function as molecular chaperones, new insights into the details by which proteins are synthesized and acquire their final biologically active conformation have been realized. Equally exciting is the progress being made as it relates the potential diagnostic and therapeutic applications of the stress-response proteins. The use of stress proteins as the next generation of vaccines and/or their use as potentially powerful adjuvants, capable of stimulating both T and B cell responses to a particular antigen of interest appear close to becoming a reality. One wonders how many more surprises are in store for us as we continue to explore this evolutionally conserved cellular stress response.

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  • Hightower LE. Cultured animal cells exposed to amino acid analogues or puromycin rapidly synthesize several polypeptides. J Cell Physiol. 1980 Mar;102(3):407–427. [PubMed]
  • Lis J, Wu C. Protein traffic on the heat shock promoter: parking, stalling, and trucking along. Cell. 1993 Jul 16;74(1):1–4. [PubMed]
  • Sistonen L, Sarge KD, Phillips B, Abravaya K, Morimoto RI. Activation of heat shock factor 2 during hemin-induced differentiation of human erythroleukemia cells. Mol Cell Biol. 1992 Sep;12(9):4104–4111. [PMC free article] [PubMed]
  • Lindquist S. The heat-shock response. Annu Rev Biochem. 1986;55:1151–1191. [PubMed]
  • Welch WJ. Mammalian stress response: cell physiology, structure/function of stress proteins, and implications for medicine and disease. Physiol Rev. 1992 Oct;72(4):1063–1081. [PubMed]
  • Pratt WB. The role of heat shock proteins in regulating the function, folding, and trafficking of the glucocorticoid receptor. J Biol Chem. 1993 Oct 15;268(29):21455–21458. [PubMed]
  • Yem AW, Tomasselli AG, Heinrikson RL, Zurcher-Neely H, Ruff VA, Johnson RA, Deibel MR., Jr The Hsp56 component of steroid receptor complexes binds to immobilized FK506 and shows homology to FKBP-12 and FKBP-13. J Biol Chem. 1992 Feb 15;267(5):2868–2871. [PubMed]
  • Sanchez ER. Hsp56: a novel heat shock protein associated with untransformed steroid receptor complexes. J Biol Chem. 1990 Dec 25;265(36):22067–22070. [PubMed]
  • Hartl FU, Martin J, Neupert W. Protein folding in the cell: the role of molecular chaperones Hsp70 and Hsp60. Annu Rev Biophys Biomol Struct. 1992;21:293–322. [PubMed]
  • Georgopoulos C, Welch WJ. Role of the major heat shock proteins as molecular chaperones. Annu Rev Cell Biol. 1993;9:601–634. [PubMed]
  • Langer T, Pfeifer G, Martin J, Baumeister W, Hartl FU. Chaperonin-mediated protein folding: GroES binds to one end of the GroEL cylinder, which accommodates the protein substrate within its central cavity. EMBO J. 1992 Dec;11(13):4757–4765. [PMC free article] [PubMed]
  • Kubota H, Hynes G, Carne A, Ashworth A, Willison K. Identification of six Tcp-1-related genes encoding divergent subunits of the TCP-1-containing chaperonin. Curr Biol. 1994 Feb 1;4(2):89–99. [PubMed]
  • Anfinsen CB. Principles that govern the folding of protein chains. Science. 1973 Jul 20;181(4096):223–230. [PubMed]
  • Ellis RJ, van der Vies SM. Molecular chaperones. Annu Rev Biochem. 1991;60:321–347. [PubMed]
  • Brugge JS. Interaction of the Rous sarcoma virus protein pp60src with the cellular proteins pp50 and pp90. Curr Top Microbiol Immunol. 1986;123:1–22. [PubMed]
  • Smith DF, Toft DO. Steroid receptors and their associated proteins. Mol Endocrinol. 1993 Jan;7(1):4–11. [PubMed]
  • Jakob U, Gaestel M, Engel K, Buchner J. Small heat shock proteins are molecular chaperones. J Biol Chem. 1993 Jan 25;268(3):1517–1520. [PubMed]
  • Miron T, Vancompernolle K, Vandekerckhove J, Wilchek M, Geiger B. A 25-kD inhibitor of actin polymerization is a low molecular mass heat shock protein. J Cell Biol. 1991 Jul;114(2):255–261. [PMC free article] [PubMed]
  • Lavoie JN, Gingras-Breton G, Tanguay RM, Landry J. Induction of Chinese hamster HSP27 gene expression in mouse cells confers resistance to heat shock. HSP27 stabilization of the microfilament organization. J Biol Chem. 1993 Feb 15;268(5):3420–3429. [PubMed]
  • Lavoie JN, Hickey E, Weber LA, Landry J. Modulation of actin microfilament dynamics and fluid phase pinocytosis by phosphorylation of heat shock protein 27. J Biol Chem. 1993 Nov 15;268(32):24210–24214. [PubMed]
  • Vass K, Berger ML, Nowak TS, Jr, Welch WJ, Lassmann H. Induction of stress protein HSP70 in nerve cells after status epilepticus in the rat. Neurosci Lett. 1989 May 22;100(1-3):259–264. [PubMed]
  • Sloviter RS, Lowenstein DH. Heat shock protein expression in vulnerable cells of the rat hippocampus as an indicator of excitation-induced neuronal stress. J Neurosci. 1992 Aug;12(8):3004–3009. [PubMed]
  • Delcayre C, Samuel JL, Marotte F, Best-Belpomme M, Mercadier JJ, Rappaport L. Synthesis of stress proteins in rat cardiac myocytes 2-4 days after imposition of hemodynamic overload. J Clin Invest. 1988 Aug;82(2):460–468. [PMC free article] [PubMed]
  • Donnelly TJ, Sievers RE, Vissern FL, Welch WJ, Wolfe CL. Heat shock protein induction in rat hearts. A role for improved myocardial salvage after ischemia and reperfusion? Circulation. 1992 Feb;85(2):769–778. [PubMed]
  • Currie RW, Tanguay RM, Kingma JG., Jr Heat-shock response and limitation of tissue necrosis during occlusion/reperfusion in rabbit hearts. Circulation. 1993 Mar;87(3):963–971. [PubMed]
  • Yellon DM, Iliodromitis E, Latchman DS, Van Winkle DM, Downey JM, Williams FM, Williams TJ. Whole body heat stress fails to limit infarct size in the reperfused rabbit heart. Cardiovasc Res. 1992 Apr;26(4):342–346. [PubMed]
  • Barbe MF, Tytell M, Gower DJ, Welch WJ. Hyperthermia protects against light damage in the rat retina. Science. 1988 Sep 30;241(4874):1817–1820. [PubMed]
  • Villar J, Edelson JD, Post M, Mullen JB, Slutsky AS. Induction of heat stress proteins is associated with decreased mortality in an animal model of acute lung injury. Am Rev Respir Dis. 1993 Jan;147(1):177–181. [PubMed]
  • Koenig WJ, Lohner RA, Perdrizet GA, Lohner ME, Schweitzer RT, Lewis VL., Jr Improving acute skin-flap survival through stress conditioning using heat shock and recovery. Plast Reconstr Surg. 1992 Oct;90(4):659–664. [PubMed]
  • Gottesman MM, Pastan I. The multidrug transporter, a double-edged sword. J Biol Chem. 1988 Sep 5;263(25):12163–12166. [PubMed]
  • Hosokawa N, Hirayoshi K, Nakai A, Hosokawa Y, Marui N, Yoshida M, Sakai T, Nishino H, Aoike A, Kawai K, et al. Flavonoids inhibit the expression of heat shock proteins. Cell Struct Funct. 1990 Dec;15(6):393–401. [PubMed]
  • Blake MJ, Udelsman R, Feulner GJ, Norton DD, Holbrook NJ. Stress-induced heat shock protein 70 expression in adrenal cortex: an adrenocorticotropic hormone-sensitive, age-dependent response. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9873–9877. [PMC free article] [PubMed]
  • Udelsman R, Blake MJ, Stagg CA, Li DG, Putney DJ, Holbrook NJ. Vascular heat shock protein expression in response to stress. Endocrine and autonomic regulation of this age-dependent response. J Clin Invest. 1993 Feb;91(2):465–473. [PMC free article] [PubMed]
  • Blake MJ, Buckley DJ, Buckley AR. Dopaminergic regulation of heat shock protein-70 expression in adrenal gland and aorta. Endocrinology. 1993 Mar;132(3):1063–1070. [PubMed]
  • DeNagel DC, Pierce SK. Heat shock proteins in immune responses. Crit Rev Immunol. 1993;13(1):71–81. [PubMed]
  • Nadler SG, Tepper MA, Schacter B, Mazzucco CE. Interaction of the immunosuppressant deoxyspergualin with a member of the Hsp70 family of heat shock proteins. Science. 1992 Oct 16;258(5081):484–486. [PubMed]
  • Young RA, Elliott TJ. Stress proteins, infection, and immune surveillance. Cell. 1989 Oct 6;59(1):5–8. [PubMed]
  • Young DB. Heat-shock proteins: immunity and autoimmunity. Curr Opin Immunol. 1992 Aug;4(4):396–400. [PubMed]
  • Ferguson A. Mucosal immunology. Immunol Today. 1990 Jan;11(1):1–3. [PubMed]
  • Blander SJ, Horwitz MA. Major cytoplasmic membrane protein of Legionella pneumophila, a genus common antigen and member of the hsp 60 family of heat shock proteins, induces protective immunity in a guinea pig model of Legionnaires' disease. J Clin Invest. 1993 Feb;91(2):717–723. [PMC free article] [PubMed]
  • Gomez FJ, Gomez AM, Deepe GS., Jr An 80-kilodalton antigen from Histoplasma capsulatum that has homology to heat shock protein 70 induces cell-mediated immune responses and protection in mice. Infect Immun. 1992 Jul;60(7):2565–2571. [PMC free article] [PubMed]
  • Dubois P, Dedet JP, Fandeur T, Roussilhon C, Jendoubi M, Pauillac S, Mercereau-Puijalon O, Pereira Da Silva L. Protective immunization of the squirrel monkey against asexual blood stages of Plasmodium falciparum by use of parasite protein fractions. Proc Natl Acad Sci U S A. 1984 Jan;81(1):229–232. [PMC free article] [PubMed]
  • Rénia L, Mattei D, Goma J, Pied S, Dubois P, Miltgen F, Nüssler A, Matile H, Menégaux F, Gentilini M, et al. A malaria heat-shock-like determinant expressed on the infected hepatocyte surface is the target of antibody-dependent cell-mediated cytotoxic mechanisms by nonparenchymal liver cells. Eur J Immunol. 1990 Jul;20(7):1445–1449. [PubMed]
  • Buchmeier NA, Heffron F. Induction of Salmonella stress proteins upon infection of macrophages. Science. 1990 May 11;248(4956):730–732. [PubMed]
  • Ensgraber M, Loos M. A 66-kilodalton heat shock protein of Salmonella typhimurium is responsible for binding of the bacterium to intestinal mucus. Infect Immun. 1992 Aug;60(8):3072–3078. [PMC free article] [PubMed]
  • Morrison RP, Belland RJ, Lyng K, Caldwell HD. Chlamydial disease pathogenesis. The 57-kD chlamydial hypersensitivity antigen is a stress response protein. J Exp Med. 1989 Oct 1;170(4):1271–1283. [PMC free article] [PubMed]
  • Shanafelt MC, Hindersson P, Soderberg C, Mensi N, Turck CW, Webb D, Yssel H, Peltz G. T cell and antibody reactivity with the Borrelia burgdorferi 60-kDa heat shock protein in Lyme arthritis. J Immunol. 1991 Jun 1;146(11):3985–3992. [PubMed]
  • Kaufmann SH. Heat shock proteins and autoimmunity: facts or fiction? Curr Biol. 1991 Dec;1(6):359–361. [PubMed]
  • Cohen IR. Autoimmunity to chaperonins in the pathogenesis of arthritis and diabetes. Annu Rev Immunol. 1991;9:567–589. [PubMed]
  • Kaufman DL, Clare-Salzler M, Tian J, Forsthuber T, Ting GS, Robinson P, Atkinson MA, Sercarz EE, Tobin AJ, Lehmann PV. Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetes. Nature. 1993 Nov 4;366(6450):69–72. [PubMed]
  • Tisch R, Yang XD, Singer SM, Liblau RS, Fugger L, McDevitt HO. Immune response to glutamic acid decarboxylase correlates with insulitis in non-obese diabetic mice. Nature. 1993 Nov 4;366(6450):72–75. [PubMed]
  • De Graeff-Meeder ER, van der Zee R, Rijkers GT, Schuurman HJ, Kuis W, Bijlsma JW, Zegers BJ, van Eden W. Recognition of human 60 kD heat shock protein by mononuclear cells from patients with juvenile chronic arthritis. Lancet. 1991 Jun 8;337(8754):1368–1372. [PubMed]
  • Li Z, Srivastava PK. Tumor rejection antigen gp96/grp94 is an ATPase: implications for protein folding and antigen presentation. EMBO J. 1993 Aug;12(8):3143–3151. [PMC free article] [PubMed]
  • Udono H, Srivastava PK. Heat shock protein 70-associated peptides elicit specific cancer immunity. J Exp Med. 1993 Oct 1;178(4):1391–1396. [PMC free article] [PubMed]
  • Lussow AR, Barrios C, van Embden J, Van der Zee R, Verdini AS, Pessi A, Louis JA, Lambert PH, Del Giudice G. Mycobacterial heat-shock proteins as carrier molecules. Eur J Immunol. 1991 Oct;21(10):2297–2302. [PubMed]
  • Barrios C, Lussow AR, Van Embden J, Van der Zee R, Rappuoli R, Costantino P, Louis JA, Lambert PH, Del Giudice G. Mycobacterial heat-shock proteins as carrier molecules. II: The use of the 70-kDa mycobacterial heat-shock protein as carrier for conjugated vaccines can circumvent the need for adjuvants and Bacillus Calmette Guérin priming. Eur J Immunol. 1992 Jun;22(6):1365–1372. [PubMed]
  • Welch WJ. How cells respond to stress. Sci Am. 1993 May;268(5):56–64. [PubMed]

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