Cell Stress and Chaperones

, Volume 16, Issue 1, pp 15–31 | Cite as

Meta-analysis of heat- and chemically upregulated chaperone genes in plant and human cells

  • Andrija Finka
  • Rayees U. H. Mattoo
  • Pierre GoloubinoffEmail author
Original Paper


Molecular chaperones are central to cellular protein homeostasis. In mammals, protein misfolding diseases and aging cause inflammation and progressive tissue loss, in correlation with the accumulation of toxic protein aggregates and the defective expression of chaperone genes. Bacteria and non-diseased, non-aged eukaryotic cells effectively respond to heat shock by inducing the accumulation of heat-shock proteins (HSPs), many of which molecular chaperones involved in protein homeostasis, in reducing stress damages and promoting cellular recovery and thermotolerance. We performed a meta-analysis of published microarray data and compared expression profiles of HSP genes from mammalian and plant cells in response to heat or isothermal treatments with drugs. The differences and overlaps between HSP and chaperone genes were analyzed, and expression patterns were clustered and organized in a network. HSPs and chaperones only partly overlapped. Heat-shock induced a subset of chaperones primarily targeted to the cytoplasm and organelles but not to the endoplasmic reticulum, which organized into a network with a central core of Hsp90s, Hsp70s, and sHSPs. Heat was best mimicked by isothermal treatments with Hsp90 inhibitors, whereas less toxic drugs, some of which non-steroidal anti-inflammatory drugs, weakly expressed different subsets of Hsp chaperones. This type of analysis may uncover new HSP-inducing drugs to improve protein homeostasis in misfolding and aging diseases.


Chaperone network Heat shock proteins Foldase NSAID Cellular stress response Unfolded protein response 



This research was financed in part by grant no. 3100A0-109290 from the Swiss National Science Foundation, the Alzheimer’s Drug Discovery Foundation New York, and the Zwahlen Grant from the Faculty of Biology and Medicine from Lausanne University.

Supplementary material

12192_2010_216_MOESM1_ESM.pdf (957 kb)
Supplemental Fig. 1 Correlation of Arabidopsis chaperome transcription in five independent heat shock treatments. Heat shock cognates are indicated by arrows. The microarray data were extracted from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus under the series accession numbers GSE4760 (Hsf2 mutant, 4 days at 23°C to 2 h at 38°C), GSE16222 (5 days at 23°C to 1 h at 37°C), GSE12619 (7 days at 22°C to 1 h at 37°C), GSE4062 (15 days at 22°C to 2 h at 37°C), and GSE11758 (mature leaves at 20°C to 1 h at 37°C) (PDF 956 kb)
12192_2010_216_MOESM2_ESM.pdf (1 mb)
Supplemental Fig. 2 Clustering of RNA expression levels of the Arabidopsis chaperome under seven abiotic and chemical treatments: dithiothreitol (DTT), tunicamycin, salicylic acid, ibuprofen, 2,3,5- triiodobenzoicacid (TIBA), 2,4,6-trihydroxybenzamide (2,4,6-T), and heat treatment as indicated. Gene clusters typical of the of the cellular stress response (CSR) (a) or of the unfolded protein response (UPR) (b) are indicated with brackets. The presumed subcellular localizations are indicated with different background colors (PDF 1032 kb)
12192_2010_216_MOESM3_ESM.pdf (442 kb)
Supplemental Fig. 3 Clustering of RNA expression levels of 168 genes from the human chaperome under 21 treatments: A 2-deoxyglucose, B tunicamycin, C phorbol 12-myristate 13-acetate, D cadmium, E N-acetylcysteine, F paclitaxel, G doxycycline, H echinomycin, I heat shock study, J elesclomol, K smoking, L simvastatin, M etoposide, N VAF347, O sapphyrin PCI-5002, P propiconazole, Q myclobutanil, R rifampicin, S dihydrotestosterone, T estrogen, and U apple procyanidin. Gene clusters typical a of the cellular stress response (CSR), b of the unfolded protein response (UPR), and c of a main less specific cell response are indicated with brackets. The presumed subcellular localizations are indicated with different background colors of the gene names (PDF 442 kb)
12192_2010_216_MOESM4_ESM.xls (46 kb)
Table 1a List of identified human chaperone genes. (1) Small HSP, GroEL and CCT-like chaperonins, Hsp70, DNAJ, Hsp100 and Hsp90 families have been previously annotated (Kampinga et al. 2009). (2) The Bag family has been previously annotated (Takayama et al. 1999). (3) FKBP and CYP like peptide-prolyl isomerase families have been previously annotated (Barik 2006). (4) Protein disulfide isomerase family has been previously annotated (Ellgaard and Ruddock 2005). (5)Human Hsp90 co-chaperones have been identified according to (XLS 45 kb)
12192_2010_216_MOESM5_ESM.xls (32 kb)
Table 1b List of identified heat shock elements (HSEs) in human chaperome. Nucleotide sequences of canonical HSEs in cis and trans orientations were identified between position −3000 and 300 bp from the translation start site of each chaperone gene (XLS 32 kb)
12192_2010_216_MOESM6_ESM.xls (162 kb)
Table 2 List of identified Arabidopsis thaliana chaperome genes. (1) Small HSPs were obtained by BLAST using α-crystalline domain as queries against the Arabidopsis protein subset of the NCBI database. (2) Chaperonins have been previously annotated (Hill and Hemmingsen 2001). (3) DnaJ proteins were re-annotated as compared to the previous J-protein nomenclature (Rajan and D’Silva 2009, as shown in brackets). All isoforms, splice variants, and paralogous protein according to previous annotations have been removed. The gene loci At2g02200, At5g34895, At2g07010 (MWJ3.6), At1g31210, At2g14930, At2g13940, and At2g24660 (corresponding to AtDjC6, AtDjC7, AtDjC50, and AtDjC58–AtDjC61, respectively) contained transposable elements and were removed as such. (4) The Hsp70 and Hsp110 were obtained by BLAST using DnaK from E. coli as query against the Arabidopsis protein subset of the NCBI database. (5) The Hsp100 were obtained by BLAST using ClpB from E. coli as the query against Arabidopsis protein subset of the NCBI database. Only the most ClpB-like proteins were retained, while ClpA/C proteins that are associated to the ClpP protease were excluded. (6) The Bag family has been previously annotated (Yan 2003). (7) The Hsp90 family has been previously annotated (Krishna and Gloor 2001). (8) PPIase families have been previously annotated (Romano et al. 2005). (9) PDIs families have been previously annotated (Houston et al. 2005). (10) Human Hsp90 co-chaperones were identified in yeast and animals according to and used as queries to identify Arabidopsis orthologs in the protein subset of the NCBI database (XLS 162 kb)
12192_2010_216_MOESM7_ESM.doc (40 kb)
ESM 1 Supplemental references (DOC 39.5 kb)


  1. Aalinkeel R, Bindukumar B, Reynolds JL, Sykes DE, Mahajan SD, Chadha KC, Schwartz SA (2008) The dietary bioflavonoid, quercetin, selectively induces apoptosis of prostate cancer cells by down-regulating the expression of heat shock protein 90. Prostate 68(16):1773–1789. doi: 10.1002/Pros.20845 PubMedCrossRefGoogle Scholar
  2. Albanese V, Yam AYW, Baughman J, Parnot C, Frydman J (2006) Systems analyses reveal two chaperone networks with distinct functions in eukaryotic cells. Cell 124(1):75–88PubMedCrossRefGoogle Scholar
  3. Amin J, Ananthan J, Voellmy R (1988) Key features of heat-shock regulatory elements. Mol Cell Biol 8(9):3761–3769PubMedGoogle Scholar
  4. Aparicio F, Thomas CL, Lederer C, Niu Y, Wang DW, Maule AJ (2005) Virus induction of heat shock protein 70 reflects a general response to protein accumulation in the plant cytosol. Plant Physiol 138(1):529–536. doi: 10.1104/pp.104.058958 PubMedCrossRefGoogle Scholar
  5. Azem A, Diamant S, Kessel M, Weiss C, Goloubinoff P (1995) The protein-folding activity of chaperonins correlates with the symmetric GroEL(14)(GroES(7))(2) heterooligomer. Proc Natl Acad Sci USA 92(26):12021–12025PubMedCrossRefGoogle Scholar
  6. Becker J, Craig EA (1994) Heat-shock proteins as molecular chaperones. Eur J Biochem 219(1–2):11–23PubMedCrossRefGoogle Scholar
  7. Ben-Zvi A, De los Rios P, Dietler G, Goloubinoff P (2004) Active solubilization and refolding of stable protein aggregates by cooperative unfolding action of individual Hsp70 chaperones. J Biol Chem 279(36):37298–37303. doi: 10.1074/jbc.M405627200 PubMedCrossRefGoogle Scholar
  8. Ben-Zvi A, Miller EA, Morimoto RI (2009) Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging. Proc Natl Acad Sci USA 106(35):14914–14919. doi: 10.1073/pnas.0902882106 PubMedCrossRefGoogle Scholar
  9. Blatch GL, Lassle M (1999) The tetratricopeptide repeat: a structural motif mediating protein–protein interactions. Bioessays 21(11):932–939PubMedCrossRefGoogle Scholar
  10. Booth CR, Meyer AS, Cong Y, Topf M, Sali A, Ludtke SJ, Chiu W, Frydman J (2008) Mechanism of lid closure in the eukaryotic chaperonin TRiC/CCT. Nat Struct Mol biol 15(7):746–753. doi: 10.1038/Nsmb.1436 PubMedCrossRefGoogle Scholar
  11. Calabrese V, Cornelius C, Mancuso C, Pennisi G, Calafato S, Bellia F, Bates TE, Stella AMG, Schapira T, Kostova ATD, Rizzarelli E (2008) Cellular stress response: a novel target for chemoprevention and nutritional neuroprotection in aging, neurodegenerative disorders and longevity. Neurochem Res 33(12):2444–2471. doi: 10.1007/s11064-008-9775-9 PubMedCrossRefGoogle Scholar
  12. Cintron NS, Toft D (2006) Defining the requirements for Hsp40 and Hsp70 in the Hsp90 chaperone pathway. J Biol Chem 281(36):26235–26244. doi: 10.1074/jbc.M605417200 PubMedCrossRefGoogle Scholar
  13. Connell P, Ballinger CA, Jiang JH, Wu YX, Thompson LJ, Hohfeld J, Patterson C (2001) The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nat Cell Biol 3(1):93–96PubMedCrossRefGoogle Scholar
  14. Csermely P (2001) Chaperone overload is a possible contributor to ‘civilization diseases’. Trends Genet 17(12):701–704PubMedCrossRefGoogle Scholar
  15. Csermely P, Korcsmáros T, Kovács IA, Szalay MS, Soti C (2008) Systems biology of molecular chaperone networks. In: Derek J, Chadwick JG (eds) The biology of extracellular molecular chaperones., pp 45–58Google Scholar
  16. Daniels CJ, Mckee AHZ, Doolittle WF (1984) Archaebacterial heat-shock proteins. EMBO J 3(4):745–749PubMedGoogle Scholar
  17. De los Rios P, Ben-Zvi A, Slutsky O, Azem A, Goloubinoff P (2006) Hsp70 chaperones accelerate protein translocation and the unfolding of stable protein aggregates by entropic pulling. Proc Natl Acad Sci USA 103(16):6166–6171. doi: 10.1073/pnas.0510496103 PubMedCrossRefGoogle Scholar
  18. de Marco A, Vigh L, Diamant S, Goloubinoff P (2005) Native folding of aggregation-prone recombinant proteins in Escherichia coli by osmolytes, plasmid- or benzyl alcohol-overexpressed molecular chaperones. Cell Stress Chaperones 10(4):329–339PubMedCrossRefGoogle Scholar
  19. Deuerling E, Schulze-Specking A, Tomoyasu T, Mogk A, Bukau B (1999) Trigger factor and DnaK cooperate in folding of newly synthesized proteins. Nature 400(6745):693–696PubMedCrossRefGoogle Scholar
  20. Diamant S, Ben-Zvi AP, Bukau B, Goloubinoff P (2000) Size-dependent disaggregation of stable protein aggregates by the DnaK chaperone machinery. J Biol Chem 275(28):21107–21113PubMedCrossRefGoogle Scholar
  21. Didelot C, Lanneau D, Brunet M, Joly AL, De Thonel A, Chiosis G, Garrido C (2007) Anti-cancer therapeutic approaches based on intracellular and extracellular heat shock proteins. Curr Med Chem 14(27):2839–2847PubMedCrossRefGoogle Scholar
  22. El-Samad H, Kurata H, Doyle JC, Gross CA, Khammash M (2005) Surviving heat shock: control strategies for robustness and performance. Proc Natl Acad Sci USA 102(8):2736–2741. doi: 10.1073/pnas.0403510102 PubMedCrossRefGoogle Scholar
  23. Ellis RJ, Vandervies SM, Hemmingsen SM (1989) The molecular chaperone concept. Biochem Soc Symp 55:145–153PubMedGoogle Scholar
  24. Fonte V, Kipp DR, Yerg J, Merin D, Forrestal M, Wagner E, Roberts CM, Link CD (2008) Suppression of in vivo beta-amyloid peptide toxicity by overexpression of the HSP-16.2 small chaperone protein. J Biol Chem 283(2):784–791. doi: 10.1074/jbc.M703339200 PubMedCrossRefGoogle Scholar
  25. Garrido C, Brunet M, Didelot C, Zermati Y, Schmitt E, Kroemer G (2006) Heat shock proteins 27 and 70. Cell Cycle 5(22):2592–2601PubMedCrossRefGoogle Scholar
  26. Gidalevitz T, Kikis EA, Morimoto RI (2010) A cellular perspective on conformational disease: the role of genetic background and proteostasis networks. Curr Opin Struck Biol 20(1):23–32. doi: 10.1016/ CrossRefGoogle Scholar
  27. Glover JR, Lindquist S (1998) Hsp104, Hsp70, and Hsp40: a novel chaperone system that rescues previously aggregated proteins. Cell 94(1):73–82PubMedCrossRefGoogle Scholar
  28. Goloubinoff P, Christeller JT, Gatenby AA, Lorimer GH (1989) Reconstitution of active dimeric ribulose bisphosphate carboxylase from an unfolded state depends on 2 chaperonin proteins and Mg-ATP. Nature 342(6252):884–889PubMedCrossRefGoogle Scholar
  29. Goloubinoff P, Mogk A, Ben Zvi AP, Tomoyasu T, Bukau B (1999) Sequential mechanism of solubilization and refolding of stable protein aggregates by a bichaperone network. Proc Natl Acad Sci USA 96(24):13732–13737PubMedCrossRefGoogle Scholar
  30. Hageman J, Kampinga HH (2009) Computational analysis of the human HSPH/HSPA/DNAJ family and cloning of a human HSPH/HSPA/DNAJ expression library. Cell Stress Chaperones 14(1):1–21. doi: 10.1007/s12192-008-0060-2 PubMedCrossRefGoogle Scholar
  31. Hageman J, Vos MJ, van Waarde MAWH, Kampinga HH (2007) Comparison of intra-organellar chaperone capacity for dealing with stress-induced protein unfolding. J Biol Chem 282(47):34334–34345. doi: 10.1074/jbc.M703876200 PubMedCrossRefGoogle Scholar
  32. Harrison C (2003) GrpE, a nucleotide exchange factor for DnaK. Cell Stress Chaperones 8(3):218–224PubMedCrossRefGoogle Scholar
  33. Hartl FU, Hayer-Hartl M (2009) Converging concepts of protein folding in vitro and in vivo. Nat Struct Mol biol 16(6):574–581. doi: 10.1038/Nsmb.1591 PubMedCrossRefGoogle Scholar
  34. Hasan CMM, Shimizu K (2008) Effect of temperature up-shift on fermentation and metabolic characteristics in view of gene expressions in Escherichia coli. Microb Cell Fact 7:35. doi:10.1186/1475-2859-7-35 Google Scholar
  35. Haslbeck M, Franzmann T, Weinfurtner D, Buchner J (2005) Some like it hot: the structure and function of small heat-shock proteins. Nat Struct Mol biol 12(10):842–846. doi: 10.1038/Nsmb993 PubMedCrossRefGoogle Scholar
  36. Hendrick JP, Hartl FU (1993) Molecular chaperone functions of heat-shock proteins. Annu Rev Biochem 62:349–384PubMedCrossRefGoogle Scholar
  37. Hightower LE (1980) Cultured animal-cells exposed to amino-acid-analogs or puromycin rapidly synthesize several polypeptides. J Cell Physiol 102(3):407–427PubMedCrossRefGoogle Scholar
  38. Hinault MP, Goloubinoff P (2007) Molecular crime and cellular punishment: active detoxification of misfolded and aggregated proteins in the cell by the chaperone and protease networks. Adv Exp Mol Biol 594:47–54CrossRefGoogle Scholar
  39. Hinault MP, Ben-Zvi A, Goloubinoff P (2006) Chaperones and proteases—cellular fold-controlling factors of proteins in neurodegenerative diseases and aging. J Mol Neurosci 30(3):249–265. doi: 10.1385/Jmn/30:03:249 PubMedCrossRefGoogle Scholar
  40. Hooper SD, Bork P (2005) Medusa: a simple tool for interaction graph analysis. Bioinformatics 21(24):4432–4433. doi: 10.1093/bioinformatics/bti696 PubMedCrossRefGoogle Scholar
  41. Horváth I, Glatz A, Varvasovszki V, Török Z, Pali T, Balogh G, Kovacs E, Nadasdi L, Benko S, Joo F, Vígh L (1998) Membrane physical state controls the signaling mechanism of the heat shock response in Synechocystis PCC 6803: identification of hsp17 as a “fluidity gene”. Proc Natl Acad Sci USA 95(7):3513–3518PubMedCrossRefGoogle Scholar
  42. Horvath I, Multhoff G, Sonnleitner A, Vigh L (2008) Membrane-associated stress proteins: more than simply chaperones. Biochim Biophys Act 1778(7–8):1653–1664. doi: 10.1016/j.bbamem.2008.02.012 CrossRefGoogle Scholar
  43. Jakob U, Gaestel M, Engel K, Buchner J (1993) Small heat-shock proteins are molecular chaperones. J Biol Chem 268(3):1517–1520PubMedGoogle Scholar
  44. Jensen LJ, Kuhn M, Stark M, Chaffron S, Creevey C, Muller J, Doerks T, Julien P, Roth A, Simonovic M, Bork P, von Mering C (2009) STRING 8—a global view on proteins and their functional interactions in 630 organisms. Nucleic Acids Res 37:D412–D416. doi: 10.1093/Nar/Gkn760 PubMedCrossRefGoogle Scholar
  45. Jolly C, Morimoto RI (2000) Role of the heat shock response and molecular chaperones in oncogenesis and cell death. J Natl Cancer Inst 92(19):1564–1572PubMedCrossRefGoogle Scholar
  46. Kabani M, McLellan C, Raynes DA, Guerriero V, Brodsky JL (2002) HspBP1, a homologue of the yeast Fes1 and S1s1 proteins, is an Hsc70 nucleotide exchange factor. FEBS Lett 531(2):339–342. doi: S0014-5793(02)03570-6 PubMedCrossRefGoogle Scholar
  47. Kabbage M, Dickman MB (2008) The BAG proteins: a ubiquitous family of chaperone regulators. Cell Mol Life Sci 65(9):1390–1402. doi: 10.1007/s00018-008-7535-2 PubMedCrossRefGoogle Scholar
  48. Kampinga HH, Hageman J, Vos MJ, Kubota H, Tanguay RM, Bruford EA, Cheetham ME, Chen B, Hightower LE (2009) Guidelines for the nomenclature of the human heat shock proteins. Cell Stress Chaperones 14(1):105–111. doi: 10.1007/s12192-008-0068-7 PubMedCrossRefGoogle Scholar
  49. Kanemura H, Kusumoto K, Miyake H, Tashiro S, Rokutan K, Shimada M (2009) Geranylgeranylacetone prevents acute liver damage after massive hepatectomy in rats through suppression of a CXC chemokine GRO1 and induction of heat shock proteins. J Gastrointest Surg 13(1):66–73. doi: 10.1007/s11605-008-0604-x PubMedCrossRefGoogle Scholar
  50. Kanitkar M, Bhonde RR (2008) Curcumin treatment enhances islet recovery by induction of heat shock response proteins, Hsp70 and heme oxygenase-1, during cryopreservation. Life Sci 82(3–4):182–189. doi: 10.1016/j.lfs.2007.10.026 PubMedCrossRefGoogle Scholar
  51. Kieran D, Kalmar B, Dick JRT, Riddoch-Contreras J, Burnstock G, Greensmith L (2004) Treatment with arimoclomol, a coinducer of heat shock proteins, delays disease progression in ALS mice. Nat Med 10(4):402–405. doi: 10.1038/Nm1021 PubMedCrossRefGoogle Scholar
  52. Kimpel JA, Key JL (1985) Presence of heat-shock mRNAs in field grown soybeans. Plant Physiol 79(3):672–678PubMedCrossRefGoogle Scholar
  53. Kirshner JR, He SQ, Balasubramanyam V, Kepros J, Yang CY, Zhang M, Du ZJ, Barsoum J, Bertin J (2008) Elesclomol induces cancer cell apoptosis through oxidative stress. Mol Cancer Ther 7(8):2319–2327. doi: 10.1158/1535-7163.Mct-08-0298 PubMedCrossRefGoogle Scholar
  54. Kitamura A, Kubota H, Pack CG, Matsumoto G, Hirayama S, Takahashi Y, Kimura H, Kinjo M, Morimoto RI, Nagata K (2006) Cytosolic chaperonin prevents polyglutamine toxicity with altering the aggregation state. Nat Cell Biol 8(10):1163–1224. doi: 10.1038/Ncb1478 PubMedCrossRefGoogle Scholar
  55. Kopito RR (2000) Aggresomes, inclusion bodies and protein aggregation. Trends Cell Biol 10(12):524–530PubMedCrossRefGoogle Scholar
  56. Kroeger PE, Morimoto RI (1994) Selection of new Hsf1 and Hsf2 DNA-binding sites reveals differences in trimer cooperativity. Mol Cell Biol 14(11):7592–7603PubMedGoogle Scholar
  57. Kumar SV, Wigge PA (2010) H2A.Z-Containing nucleosomes mediate the thermosensory response in Arabidopsis. Cell 140(1):136–147. doi: 10.1016/j.cell.2009.11.006 PubMedCrossRefGoogle Scholar
  58. Lanka V, Wieland S, Barber J, Cudkowicz M (2009) Arimoclomol: a potential therapy under development for ALS. Expert Opin Investig Drugs 18(12):1907–1918. doi: 10.1517/13543780903357486 PubMedCrossRefGoogle Scholar
  59. Large AT, Goldberg MD, Lund PA (2009) Chaperones and protein folding in the archaea. Biochem Soc Trans 37:46–51. doi: 10.1042/Bst0370046 PubMedCrossRefGoogle Scholar
  60. Lashuel HA, Hartley D, Petre BM, Walz T, Lansbury PT (2002) Neurodegenerative disease—amyloid pores from pathogenic mutations. Nature 418(6895):291PubMedCrossRefGoogle Scholar
  61. Laskey RA, Honda BM, Mills AD, Finch JT (1978) Nucleosomes are assembled by an acidic protein which binds histones and transfers them to DNA. Nature 275(5679):416–420PubMedCrossRefGoogle Scholar
  62. Liberek K, Georgopoulos C (1993) Autoregulation of the Escherichia coli heat-shock response by the Dnak and Dnaj heat-shock proteins. Proc Natl Acad Sci USA 90(23):11019–11023PubMedCrossRefGoogle Scholar
  63. Liberek K, Lewandowska A, Zietkiewicz S (2008) Chaperones in control of protein disaggregation. EMBO J 27(2):328–335. doi: 10.1038/sj.emboj.7601970 PubMedCrossRefGoogle Scholar
  64. Macario AJL, de Macario EC (1999) The archaeal molecular chaperone machine: peculiarities and paradoxes. Genetics 152(4):1277–1283PubMedGoogle Scholar
  65. Mogk A, Tomoyasu T, Goloubinoff P, Rudiger S, Roder D, Langen H, Bukau B (1999) Identification of thermolabile Escherichia coli proteins: prevention and reversion of aggregation by DnaK and ClpB. EMBO J 18(24):6934–6949PubMedCrossRefGoogle Scholar
  66. Mogk A, Hasiberger T, Tessarz P, Bukau B (2008) Common and specific mechanisms of AAA plus proteins involved in protein quality control. Biochem Soc Trans 36:120–125. doi: 10.1042/Bst0360120 PubMedCrossRefGoogle Scholar
  67. Morimoto RI (2008) Proteotoxic stress and inducible chaperone networks in neurodegenerative disease and aging. Gen Dev 22(11):1427–1438. doi: 10.1101/Gad.1657108 CrossRefGoogle Scholar
  68. Motohashi K, Watanabe Y, Yohda M, Yoshida M (1999) Heat-inactivated proteins are rescued by the DnaK.J-GrpE set and ClpB chaperones. Proc Natl Acad Sci USA 96(13):7184–7189PubMedCrossRefGoogle Scholar
  69. Nakamoto H, Vigh L (2007) The small heat shock proteins and their clients. Cell Mol Life Sci 64(3):294–306. doi: 10.1007/s00018-006-6321-2 PubMedCrossRefGoogle Scholar
  70. Narayanan NK, Narayanan BA, Bosland M, Condon MS, Nargi D (2006) Docosahexaenoic acid in combination with celecoxib modulates HSP70 and p53 proteins in prostate cancer cells. Int J Cancer 119(7):1586–1598. doi: 10.1002/Ijc.22031 PubMedCrossRefGoogle Scholar
  71. Nardai G, Csermely P, Soti C (2002) Chaperone function and chaperone overload in the aged. A preliminary analysis. Exp Gerontol 37(10–11):1257–1262. doi: S0531-5565(02)00134-1 PubMedCrossRefGoogle Scholar
  72. Onuoha SC, Couistock ET, Grossmann JG, Jackson SE (2008) Structural studies on the co-chaperone hop and its complexes with Hsp90. J Mol Biol 379(4):732–744. doi: 10.1016/j.jmb.2008.02.013 PubMedCrossRefGoogle Scholar
  73. Palotai R, Szalay MS, Csermely P (2008) Chaperones as integrators of cellular networks: changes of cellular integrity in stress and diseases. IUBMB Life 60(1):10–18. doi: 10.1002/Iub.8 PubMedCrossRefGoogle Scholar
  74. Pelham HRB (1986) Speculations on the functions of the major heat-shock and glucose-regulated proteins. Cell 46(7):959–961PubMedCrossRefGoogle Scholar
  75. Perrin V, Regulier E, Abbas-Terki T, Hassig R, Brouillet E, Aebischer P, Luthi-Carter R, Deglon N (2007) Neuroprotection by Hsp104 and Hsp27 in lentiviral-based rat models of Huntington’s disease. Mol Ther 15(5):903–911. doi: 10.1038/ PubMedCrossRefGoogle Scholar
  76. Picard D (2006) Chaperoning steroid hormone action. Trends Endocrinol Metab 17(6):229–235. doi: 10.1016/j.tem.2006.06.003 PubMedCrossRefGoogle Scholar
  77. Pouppirt PS (1929) Treatment of Parkinson’s syndrome with fever produced by baths: report of case. Cal West Med 31(3):192–195PubMedGoogle Scholar
  78. Rodriguez F, Arsene-Ploetze F, Rist W, Rudiger S, Schneider-Mergener J, Mayer MP, Bukau B (2008) Molecular basis for regulation of the heat shock transcription factor sigma(32) by the DnaK and DnaJ chaperones. Mol Cell 32(3):347–358. doi: 10.1016/j.molcel.2008.09.016 PubMedCrossRefGoogle Scholar
  79. Ross CA, Poirier MA (2004) Protein aggregation and neurodegenerative disease. Nat Rev Neurosci 10(Suppl):S10–S17. doi:10.1038/Nm1066 Google Scholar
  80. Saidi Y, Finka A, Chakhporanian M, Zryd JP, Schaefer DG, Goloubinoff P (2005) Controlled expression of recombinant proteins in Physcomitrella patens by a conditional heat-shock promoter: a tool for plant research and biotechnology. Plant Mol Biol 59(5):697–711. doi: 10.1007/s11103-005-0889-z PubMedCrossRefGoogle Scholar
  81. Saidi Y, Domini M, Choy F, Zryd JP, Schwitzguebel JP, Goloubinoff P (2007) Activation of the heat shock response in plants by chlorophenols: transgenic Physcomitrella patens as a sensitive biosensor for organic pollutants. Plant Cell Environ 30(6):753–763. doi: 10.1111/j.1365-3040.2007.01664.x PubMedCrossRefGoogle Scholar
  82. Saidi Y, Finka A, Muriset M, Bromberg Z, Weiss YG, Maathuis FJM, Goloubinoff P (2009) The heat shock response in moss plants is regulated by specific calcium-permeable channels in the plasma membrane. Plant Cell 21(9):2829–2843. doi: 10.1105/tpc.108.065318 PubMedCrossRefGoogle Scholar
  83. Saldanha AJ (2004) Java Treeview—extensible visualization of microarray data. Bioinformatics 20(17):3246–3248. doi: 10.1093/bioinformatics/bth349 PubMedCrossRefGoogle Scholar
  84. Sanchez Y, Lindquist SL (1990) Hsp104 required for induced thermotolerance. Science 248(4959):1112–1115PubMedCrossRefGoogle Scholar
  85. Sato T, Minagawa S, Kojima E, Okamoto N, Nakamoto H (2010) HtpG, the prokaryotic homologue of Hsp90, stabilizes a phycobilisome protein in the cyanobacterium Synechococcus elongatus PCC 7942. Mol Microbiol 76(3):576–589. doi: 10.1111/j.1365-2958.2010.07139.x PubMedCrossRefGoogle Scholar
  86. Schroder M, Kaufman RJ (2005) The mammalian unfolded protein response. Annu Rev Biochem 74:739–789. doi: 10.1146/annurev.biochem.73.011303.074134 PubMedCrossRefGoogle Scholar
  87. Schuermann JP, Jiang JW, Cuellar J, Llorca O, Wang LP, Gimenez LE, Jin SP, Taylor AB, Demeler B, Morano KA, Hart PJ, Valpuesta JM, Lafer EM, Sousa R (2008) Structure of the Hsp110: Hsc70 nucleotide exchange machine. Mol Cell 31(2):232–243. doi: 10.1016/j.molcel.2008.05.006 PubMedCrossRefGoogle Scholar
  88. Shaner L, Morano KA (2007) All in the family: atypical Hsp70 chaperones are conserved modulators of Hsp70 activity. Cell Stress Chaperones 12(1):1–8PubMedCrossRefGoogle Scholar
  89. Sharma SK, Christen P, Goloubinoff P (2009) Disaggregating chaperones: an unfolding story. Curr Prot Pept Sci 10:432–446CrossRefGoogle Scholar
  90. Shi LX, Theg SM (2010) A stromal heat shock protein 70 system functions in protein import into chloroplasts in the moss Physcomitrella patens. Plant Cell 22(1):205–220. doi: 10.1105/tpc.109.071464 PubMedCrossRefGoogle Scholar
  91. Shorter J, Lindquist S (2008) Hsp104, Hsp70 and Hsp40 interplay regulates formation, growth and elimination of Sup35 prions. EMBO J 27(20):2712–2724. doi: 10.1038/emboj.2008.194 PubMedCrossRefGoogle Scholar
  92. Shtilerman M, Lorimer GH, Englander SW (1999) Chaperonin function: folding by forced unfolding. Science 284(5415):822–825PubMedCrossRefGoogle Scholar
  93. Sinha RA, Khare P, Rai A, Maurya SK, Pathak A, Mohan V, Nagar GK, Mudiam MKR, Godbole MM, Bandyopadhyay S (2009) Anti-apoptotic role of omega-3-fatty acids in developing brain: perinatal hypothyroid rat cerebellum as apoptotic model. Int J Dev Neurosci 27(4):377–383. doi: 10.1016/j.ijdevneu.2009.02.003 PubMedCrossRefGoogle Scholar
  94. Smalley WE, Ray WA, Daugherty JR, Griffin MR (1995) Nonsteroidal antiinflammatory drugs and the incidence of hospitalizations for peptic-ulcer disease in elderly persons. Am J Epidemiol 141(6):539–545PubMedGoogle Scholar
  95. Solit DB, Chiosis G (2008) Development and application of Hsp90 inhibitors. Drug Discov Today 13(1–2):38–43PubMedCrossRefGoogle Scholar
  96. Soll J (2002) Protein import into chloroplasts. Curr Opin Plant Biol 5(6):529–535PubMedCrossRefGoogle Scholar
  97. Soti C, Pal C, Papp B, Csermely P (2005) Molecular chaperones as regulatory elements of cellular networks. Curr Opin Cell Biol 17(2):210–215. doi: 10.1016/ PubMedCrossRefGoogle Scholar
  98. Szabadkai G, Bianchi K, Varnai P, De Stefani D, Wieckowski MR, Cavagna D, Nagy AI, Balla T, Rizzulo R (2006) Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels. J Cell Biol 175(6):901–911PubMedCrossRefGoogle Scholar
  99. Szalay MS, Kovacs IA, Korcsmaros T, Bode C, Csermely P (2007) Stress-induced rearrangements of cellular networks: consequences for protection and drug design. FEBS Lett 581(19):3675–3680. doi: 10.1016/j.1ebsiet.2007.03.083 PubMedCrossRefGoogle Scholar
  100. Tarun AS, Peng X, Dumpit RF, Ogata Y, Silva-Rivera H, Camargo N, Daly TM, Bergman LW, Kappe SHI (2008) A combined transcriptome and proteome survey of malaria parasite liver stages. Proc Natl Acad Sci USA 105(1):305–310. doi: 10.1073/pnas.0710780104 PubMedCrossRefGoogle Scholar
  101. Tissieres A, Mitchell HK, Tracy UM (1974) Protein synthesis in salivary glands of Drosophila melanogaster—relation to chromosome puffs. J Mol Biol 84(3):389–398PubMedCrossRefGoogle Scholar
  102. Tomoyasu T, Mogk A, Langen H, Goloubinoff P, Bukau B (2001) Genetic dissection of the roles of chaperones and proteases in protein folding and degradation in the Escherichia coli cytosol. Mol Microbiol 40(2):397–413PubMedCrossRefGoogle Scholar
  103. van der Spuy J, Kana BD, Dirr HW, Blatch GL (2000) Heat shock cognate protein 70 chaperone-binding site in the co-chaperone murine stress-inducible protein 1 maps to within three consecutive tetratricopeptide repeat motifs. Biochem J 345:645–651CrossRefGoogle Scholar
  104. Veinger L, Diamant S, Buchner J, Goloubinoff P (1998) The small heat-shock protein IbpB from Escherichia coli stabilizes stress-denatured proteins for subsequent refolding by a multichaperone network. J Biol Chem 273(18):11032–11037PubMedCrossRefGoogle Scholar
  105. Vigh L, Literati PN, Horvath I, Torok Z, Balogh G, Glatz A, Kovacs E, Boros I, Ferdinandy P, Farkas B, Jaszlits L, Jednakovits A, Koranyi L, Maresca B (1997) Bimoclomol: a nontoxic, hydroxylamine derivative with stress protein-inducing activity and cytoprotective effects. Nat Med 3(10):1150–1154PubMedCrossRefGoogle Scholar
  106. Vigh L, Maresca B, Harwood JL (1998) Does the membrane’s physical state control the expression of heat shock and other genes? Trends Biochem Sci 23(10):369–374PubMedCrossRefGoogle Scholar
  107. Vigh L, Horvath I, Maresca B, Harwood JL (2007) Can the stress protein response be controlled by ‘membrane-lipid therapy’? Trends Biochem Sci 32(8):357–363. doi: 10.1016/j.tibs.2007.06.009 PubMedCrossRefGoogle Scholar
  108. Voellmy R, Boellmann F (2007) Chaperone regulation of the heat shock protein response. Adv Exp Mol Biol 594:89–99CrossRefGoogle Scholar
  109. Weiss YG, Bromberg Z, Raj N, Raphael J, Goloubinoff P, Ben-Neriah Y, Deutschman CS (2007) Enhanced heat shock protein 70 expression alters proteasomal degradation of I kappa B kinase in experimental acute respiratory distress syndrome. Crit Care Med 35(9):2128–2138. doi: 10.1097/01.Ccm.0000278915.78030.74 PubMedCrossRefGoogle Scholar
  110. Whelan SA, Hightower LE (1985) Induction of stress proteins in chicken-embryo cells by low-level zinc contamination in amino acid-free media. J Cell Physiol 122(2):205–209PubMedCrossRefGoogle Scholar
  111. Whitesell L, Lindquist SL (2005) HSP90 and the chaperoning of cancer. Nat Rev Cancer 5(10):761–772PubMedCrossRefGoogle Scholar
  112. Whitesell L, Mimnaugh EG, Decosta B, Myers CE, Neckers LM (1994) Inhibition of heat-shock protein Hsp90-Pp60(V-Src) heteroprotein complex-formation by benzoquinone ansamycins—essential role for stress proteins in oncogenic transformation. Proc Natl Acad Sci USA 91(18):8324–8328PubMedCrossRefGoogle Scholar
  113. Wickner RB (1994) [Ure3] as an altered Ure2 protein—evidence for a prion analog in Saccharomyces cerevisiae. Science 264(5158):566–569PubMedCrossRefGoogle Scholar
  114. Wiech H, Buchner J, Zimmermann R, Jakob U (1992) Hsp90 chaperones protein folding in vitro. Nature 358(6382):169–170PubMedCrossRefGoogle Scholar
  115. Wu YJ, Cao ZM, Klein WL, Luo Y (2010) Heat shock treatment reduces beta amyloid toxicity in vivo by diminishing oligomers. Neurobiol Aging 31(6):1055–1058. doi: 10.1016/j.neurobiolaging.2008.07.013 PubMedCrossRefGoogle Scholar
  116. Xing HY, Wilkerson DC, Mayhew CN, Lubert EJ, Skaggs HS, Goodson ML, Hong YL, Park-Sarge OK, Sarge KD (2005) Mechanism of Hsp70i gene bookmarking. Science 307(5708):421–423. doi: 10.1126/science.1106478 PubMedCrossRefGoogle Scholar
  117. Yamamoto N, Takemori Y, Sakurai M, Sugiyama K, Sakurai H (2009) Differential recognition of heat shock elements by members of the heat shock transcription factor family. FEBS J 276(7):1962–1974. doi: 10.1111/j.1742-4658.2009.06923.x PubMedCrossRefGoogle Scholar
  118. Yao J, Munson KM, Webb WW, Lis JT (2006) Dynamics of heat shock factor association with native gene loci in living cells. Nature 442(7106):1050–1053. doi: 10.1038/Nature05025 PubMedCrossRefGoogle Scholar
  119. Zhao RM, Davey M, Hsu YC, Kaplanek P, Tong A, Parsons AB, Krogan N, Cagney G, Mai D, Greenblatt J, Boone C, Emili A, Houry WA (2005) Navigating the chaperone network: an integrative map of physical and genetic interactions mediated by the Hsp90 chaperone. Cell 120(5):715–727. doi: 10.1016/j.cell.2004.12.024 PubMedCrossRefGoogle Scholar
  120. Zimmermann P, Hirsch-Hoffmann M, Hennig L, Gruissem W (2004) GENEVESTIGATOR. Arabidopsis microarray database and analysis toolbox. Plant Physiol 136(1):2621–2632. doi: 10.1104/pp.104.046367 PubMedCrossRefGoogle Scholar
  121. Zimmermann R, Eyrisch S, Ahmad M, Helms V (2010) Protein translocation across the ER membrane. Biochim Biophys Acta. doi: 10.1016/j.bbamem.2010.06.015 Google Scholar
  122. Zourlidou A, Smith MDP, Latchman DS (2004) HSP27 but not HSP70 has a potent protective effect against alpha-synuclein-induced cell death in mammalian neuronal cells. J Neurochem 88(6):1439–1448. doi: 10.1046/j.1471-4159.2003.02273.x PubMedCrossRefGoogle Scholar

Copyright information

© Cell Stress Society International 2010

Authors and Affiliations

  • Andrija Finka
    • 1
  • Rayees U. H. Mattoo
    • 1
  • Pierre Goloubinoff
    • 1
    Email author
  1. 1.Department of Plant Molecular BiologyUniversity of LausanneLausanneSwitzerland

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