Skip to main content
SpringerLink
Log in
Book cover

Molecular Chaperones in Health and Disease pp 1–42Cite as

Chaperones in Preventing Protein Denaturation in Living Cells and Protecting Against Cellular Stress

  • Chapter

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 172))

Abstract

A variety of cellular internal and external stress conditions can be classified as proteotoxic stresses. Proteotoxic stresses can be defined as stresses that increase the fraction of proteins that are in an unfolded state, thereby enhancing the probability of the formation of intracellular aggregates. These aggregates, if not disposed, can lead to cell death. In response to the appearance of damaged proteins, cells induce the expression of heat shock proteins. These can function as molecular chaperones to prevent protein aggregation and to keep proteins in a state competent for either refolding or degradation. Most knowledge of the function and regulation (by co-factors) of individual heat shock proteins comes from cell free studies on refolding of heat- or chemically denatured, purified proteins. Unlike the experimental situation in a test tube, cells contain multiple chaperones and co-factors often moving in and out different subcompartments that contain a variety of protein substrates at different foling states. Also, within cells folding competes with the degradative machinery. In this chapter, an overview will be provided on how the main cytosolic/nuclear chaperone Hsp70 is regulated, what is known about its interaction with other main cytosolic/nuclear chaperone families (Hsp27, Hsp90, and Hsp110), and how it may function as a molecular chaperone in living mammalian cells to protect against proteotoxic stresses.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   329.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Aki T, Yoshida K, Mizukami Y (2003) The mechanism of alphaB-crystallin gene expression by proteasome inhibition. Biochem Biophys Res Commun 311:162–167

    Article  PubMed  CAS  Google Scholar 

  • Anderson RL, Shiu E, Fisher GA, Hahn GM (1988) DNA damage does not appear to be a trigger for thermotolerance in mammalian cells. Int J Radiat Biol 54:285–298

    PubMed  CAS  Google Scholar 

  • Anderson RL, Van Kersteren I, Kraft PE, Hahn GM (1989) Biochemical analysis of heatresistant mouse tumor cell strains: a new member of the HSP70 family. Mol Cell Biol 9:3509–3516

    PubMed  CAS  Google Scholar 

  • Anfinsen CB (1973) Principles that govern folding of protein chains. Science 181:223–230

    PubMed  CAS  Google Scholar 

  • Angelidis CE, Lazaridis I, Pagoulatos GN (1991) Constitutive expression of heat-shock protein 70 in mammalian cells confers thermoresistance. Eur J Biochem 199:35–39

    Article  PubMed  CAS  Google Scholar 

  • Arrasate M, Mitra S, Schweitzer ES, Segal MR, Finkbeiner S (2004) Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 431:805–810

    Article  PubMed  CAS  Google Scholar 

  • Arrigo AP, Suhan JP, Welch WJ (1988) Dynamic changes in the structure and intracellular locale of the mammalian low-molecular-weight heat shock protein. Mol Cell Biol 8:5059–5071

    PubMed  CAS  Google Scholar 

  • Asea A, Kraeft SK, Kurt-Jones EA, Stevenson MA, Chen LB, Finberg RW, Koo GC, Calderwood SK (2000) HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med 6:435–442

    PubMed  CAS  Google Scholar 

  • Bailey CK, Andriola IF, Kampinga HH, Merry DE (2002) Molecular chaperones enhance the degradation of expanded polyglutamine repeat androgen receptor in a cellularmodel of spinal and bulbar muscular atrophy. Hum Mol Genet 11: 515–523

    Article  PubMed  CAS  Google Scholar 

  • Ballinger CA, Connell P, Wu Y, Hu Z, Thompson LJ, Yin LY, Patterson C (1999) Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions. Mol Cell Biol 19:4535–4545

    PubMed  CAS  Google Scholar 

  • Bardelli A, Longati P, Albero D, Goruppi S, Schneider C, Ponzetto C, Comoglio PM (1996) HGF receptor associates with the anti-apoptotic protein BAG-1 and prevents cell death. EMBO J 15:6205–6212

    PubMed  CAS  Google Scholar 

  • Beere HM, Wolf BB, Cain K, Mosser DD, Mahboubi A, Kuwana T, Tailor P, Morimoto RI, Cohen GM, Green DR (2000) Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat Cell Biol 2:469–475

    PubMed  CAS  Google Scholar 

  • Beissinger M, Buchner J (1998) How chaperones fold proteins. Biol Chem 379:245–259

    PubMed  CAS  Google Scholar 

  • Benaroudj N, Fouchaq B, Ladjimi MM (1997) The COOH-terminal peptide binding domain is essential for self-association of the molecular chaperone HSC70. J Biol Chem 272:8744–8751

    PubMed  CAS  Google Scholar 

  • Bercovich B, Stancovski I, Mayer A, Blumenfeld N, Laszlo A, Schwartz AL, Ciechanover A (1997) Ubiquitin-dependent degradation of certain protein substrates in vitro requires the molecular chaperone Hsc70. J Biol Chem 272:9002–9010

    PubMed  CAS  Google Scholar 

  • Bimston D, Song JH, Winchester D, Takayama S, Reed JC, Morimoto RI (1998) BAG-1, a negative regulator of Hsp70 chaperone activity, uncouples nucleotide hydrolysis from substrate release. EMBO J 17:6871–6878

    Article  PubMed  CAS  Google Scholar 

  • Boorstein WR, Ziegelhoffer T, Craig EA (1994) Molecular evolution of the Hsp70 multigene family. J Mol Evol 38:1–17

    Article  PubMed  CAS  Google Scholar 

  • Bose S, Weikl T, Bugl H, Buchner J (1996) Chaperone function of Hsp90-associated proteins. Science 274: 1715–1717

    Article  PubMed  CAS  Google Scholar 

  • Botzler C, Issels R, Multhoff G (1996) Heat-shock protein 72 cell-surface expression on human lung carcinoma cells is associated with an increased sensitivity to lysis mediated by adherent natural killer cells. Cancer Immunol Immunother 43:226–230

    Article  PubMed  CAS  Google Scholar 

  • Brown CR, Hong-Brown LQ, Doxsey SJ, Welch WJ (1996) Molecular chaperones and the centrosome. A role for HSP 73 in centrosomal repair following heat shock treatment. J Biol Chem 271:833–840

    PubMed  CAS  Google Scholar 

  • Bryantsev AL, Loktionova SA, Ilyinskaya OP, Tararak EM, Kampinga HH, Kabakov AE (2002) Distribution, phosphorylation, and activities of Hsp25 in heat-stressed H9c2 myoblasts: a functional link to cytoprotection. Cell Stress Chaperones. 7:146–155

    Article  PubMed  CAS  Google Scholar 

  • Brychzy A, Rein T, Winklhofer KF, Hartl FU, Young JC, Obermann WM (2003) Cofactor Tpr2 combines two TPR domains and a J domain to regulate the Hsp70/Hsp90 chaperone system. EMBO J 22:3613–3623

    Article  PubMed  CAS  Google Scholar 

  • Buchberger A, Valencia A, Mcmacken R, Sander C, Bukau B (1994) The chaperone function of DnaK requires the coupling of ATPase activity with substrate binding through residue E171. EMBO J 13:1687–1695

    PubMed  CAS  Google Scholar 

  • Buchberger A, Theyssen H, Schroder H, Mccarty JS, Virgallita G, Milkereit P, Reinstein J, Bukau B (1995) Nucleotide-induced conformational changes in theATPase and substrate binding domains of the DnaK chaperone provide evidence for interdomain communication. J Biol Chem 270:16903–16910

    PubMed  CAS  Google Scholar 

  • Buchner J (1996) Supervising the fold: functional principles of molecular chaperones. FASEB J 10:10–19

    PubMed  CAS  Google Scholar 

  • Buchner J, Schmidt M, Fuchs M, Jaenicke R, Rudolph R, Schmid FX, Kiefhaber T (1991) GroE facilitates refolding of citrate synthase by suppressing aggregation. Biochemistry 30:1586–1591

    PubMed  CAS  Google Scholar 

  • Bukau B, Horwich AL (1998) The Hsp70 and Hsp60 chaperone machines. Cell 92:351–366

    Article  PubMed  CAS  Google Scholar 

  • Burgman PWJJ, Konings AWT (1992) Heat induced protein denaturation in the particulate fraction of HeLa S3 cells: effects of thermotolerance. J Cell Physiol 153:88–94

    Article  PubMed  CAS  Google Scholar 

  • Cheetham ME, Brion JP, Anderton BH (1992) Human homologues of the bacterial heatshock protein DnaJ are preferentially expressed in neurons. Biochem J 284:469–476

    PubMed  CAS  Google Scholar 

  • Cheetham ME, Caplan AJ (1998) Structure, function and evolution of DnaJ: conservation and adaptation of chaperone function. Cell Stress Chaperones. 3:28–36

    Article  PubMed  CAS  Google Scholar 

  • Chen SY, Smith DF (1998) Hop as an adaptor in the heat shock protein 70 (Hsp70) and Hsp90 chaperone machinery. J Biol Chem 273:35194–35200

    PubMed  CAS  Google Scholar 

  • Chen SY, Sullivan WP, Toft DO, Smith DF (1998) Differential interactions of p23 and the TPR-containing proteins Hop, Cyp40, FKBP52 and FKBP51 with Hsp90 mutants. Cell Stress Chaperones 3:118–129

    Article  PubMed  CAS  Google Scholar 

  • Ciavarra RP, Goldman C, Wen KK, Tedeschi B, Castora FJ (1994) Heat stress induces Hsc70/nuclear topoisomerase I complex formationinvivo: evidence for Hsc70-mediated, ATP-independent reactivation in vitro. Proc Natl Acad Sci U S A 91:1751–1755

    PubMed  CAS  Google Scholar 

  • Connell P, Ballinger CA, Jiang J, Wu Y, Thompson LJ, Hohfeld J, Patterson C (2001) The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nat Cell Biol 3:93–96

    PubMed  CAS  Google Scholar 

  • Craig E, Ziegelhoffer T, Nelson J, Laloraya S, Halladay J (1995) Complex multigene family of functionally distinct Hsp70s of yeast. Cold Spring Harb Symp Quant Biol 60:441–449

    PubMed  CAS  Google Scholar 

  • Cummings CJ, Mancini MA, Antalffy B, Defranco DB, Orr HT, Zoghbi HY (1998) Chaperone suppressionof aggregationand alteredsubcellular proteasome localizationimply protein misfolding in SCA1. Nat Gen 19:148–154

    CAS  Google Scholar 

  • Demand J, Luders J, Hohfeld J (1998) The carboxy-terminal domain of Hsc70 provides binding sites for a distinct set of chaperone cofactors. Mol Cell Biol 18:2023–2028

    PubMed  CAS  Google Scholar 

  • Demand J, Alberti S, Patterson C, Hohfeld J (2001) Cooperation of a ubiquitin domain protein and an E3 ubiquitin ligase during chaperone/proteasome coupling. Curr Biol 11:1569–1577

    Article  PubMed  CAS  Google Scholar 

  • Den Engelsman J, Keijsers V, de Jong WW, Boelens WC (2003) The small heat-shock protein alpha B-crystallin promotes FBX4-dependent ubiquitination. J BiolChem 278:4699–4704

    Google Scholar 

  • Dewey WC, Li X, Wong RSL (1990) Cell killing, chromosomal aberrations, and division delay as thermal sensitivity is modified during the cell cycle. Radiat Res 122:268–274

    PubMed  CAS  Google Scholar 

  • Dikomey E, Jung H (1992) Effect of thermotolerance and step-down heating on thermal radiosensitization in CHO cells. Int J Radiat Biol 61:235–242

    PubMed  CAS  Google Scholar 

  • Dubois MF, Hovanessian AG, Bensaude O (1991) Heat-shock-induced denaturation of proteins. Characterization of the insolubilization of the interferon-induced p68 kinase. J Biol Chem 266:9707–9711

    PubMed  CAS  Google Scholar 

  • Dundr M, Misteli T, Olson MO (2000) The dynamics of postmitotic reassembly of the nucleolus. J Cell Biol 150:433–446

    Article  PubMed  CAS  Google Scholar 

  • Ehrnsperger M, Graber S, Gaestel M, Buchner J (1997) Binding of non-native protein to Hsp25 during heat shock creates a reservoir of folding intermediates for reactivation. EMBO J 16:221–229

    Article  PubMed  CAS  Google Scholar 

  • Ekedahl J, Joseph B, Marchetti P, Fauvel H, Formstecher P, Lewensohn R, Zhivotovsky B (2003) Heat shock protein 72 does not modulate ionizing radiation-induced apoptosis in U1810 non-small cell lung carcinoma cells. Cancer Biol Ther 2:663–669

    PubMed  CAS  Google Scholar 

  • Ellis RJ, Hemmingsen SM (1989) Molecular chaperones: proteins essential for the biogenesis of some macromolecular structures. TIBS 14:339–342

    PubMed  CAS  Google Scholar 

  • Ellis RJ, Van der Vies SM (1991) Molecular chaperones. Annu Rev Biochem 60:321–347

    Article  PubMed  CAS  Google Scholar 

  • Evan GI, Hancock DC (1985) Studies on the interaction of the human c-myc proteinwith cell nuclei: p62c-myc as a member of a discrete subset of nuclear proteins. Cell 43:253–261

    Article  PubMed  CAS  Google Scholar 

  • Fortin A, Raybaud-Diogene H, Tetu B, Deschenes R, Huot J, Landry J (2000) Overexpression of the 27 kDa heat shock protein is associated with thermoresistance and chemoresistance but not with radioresistance. Int J Radiat Oncol Biol Phys 46:1259–1266

    Article  PubMed  CAS  Google Scholar 

  • Fourie AM, Hupp TR, Lane DP, Sang BC, Barbosa MS, Sambrook JF, Gething MJH (1997) HSP70 binding sites in the tumor suppressor protein p53. J Biol Chem 272:19471–19479

    Article  PubMed  CAS  Google Scholar 

  • Freeman BC, Morimoto RI (1996) The human cytosolic molecular chaperones hsp90, Hsp70 (hsc70) and hdj-1 have distinct roles in recognition of a non-native protein and protein refolding. EMBO J 15:2969–2979

    PubMed  CAS  Google Scholar 

  • Freeman BC, Myers MP, Schumacher R, Morimoto RI (1995) Identification of a regulatory motif in Hsp7O that affects ATPase activity, substrate binding and interaction with HDJ-1. EMBO J 14:2281–2292

    PubMed  CAS  Google Scholar 

  • Freeman BC, Toft DO, Morimoto RI (1996) Molecular chaperone machines: chaperone activities of the cyclophilin Cyp-40 and the steroid aporeceptor-associated protein p23. Science 274:1718–1720

    Article  PubMed  CAS  Google Scholar 

  • Freeman ML, Spitz DR, Meredith MJ (1990) Does heat shock enhance oxidative stress? Studies with ferrous and ferric iron. Radiat Res 124:288–293

    PubMed  CAS  Google Scholar 

  • Friedman DI, Olson ER, Georgopoulos C, Tilly K, Herskowitz I, Banuett F (1984) Interactions of bacteriophage and host macromolecules in the growth of bacteriophage-lambda. Microbiol Rev 48:299–325

    PubMed  CAS  Google Scholar 

  • Frydman J, Nimmesgern E, Ohtsuka K, Hartl FU (1994) Folding of nascent polypeptide chains in a high molecular mass assembly with molecular chaperones. Nature 370:111–117

    Article  PubMed  CAS  Google Scholar 

  • Gabai VL, Meriin AB, Mosser DD, Caron AW, Rits S, Shifrin VI, Sherman MY (1997) Hsp70 prevents activation of stress kinases-a novel pathway of cellular thermotolerance. J Biol Chem 272:18033–18037

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Mata R, Bebok Z, Sorscher EJ, Sztul ES (1999) Characterization and dynamics of aggresome formation by a cytosolic GFP-chimera. J Cell Biol 146:1239–1254

    Article  PubMed  CAS  Google Scholar 

  • Gebauer M, Zeiner M, Gehring U (1997) Proteins interacting with the molecular chaperone hsp70/hsc70: physical associations and effects on refolding activity. FEBS Lett 417:109–113

    Article  PubMed  CAS  Google Scholar 

  • Gebauer M, Melki R, Gehring U (1998a) The chaperone cofactor Hop/p60 interacts with the cytosolic chaperonin-containing TCP-1 and affects its nucleotide exchange and protein folding activities. J Biol Chem 273: 29475–29480

    Article  PubMed  CAS  Google Scholar 

  • Gebauer M, Zeiner M, Gehring U (1998b) Interference between proteins Hap46 and Hop/p60, which bind to different domains of the molecular chaperone hsp70/hsc70. Mol. Cell Biol 18:6238–6244

    PubMed  CAS  Google Scholar 

  • Gehrmann M, Marienhagen J, Eichholtz-Wirth H, Fritz E, Ellwart J, Jaattela M, Zilch T, Multhoff G (2005) Dual function of membrane-bound heat shock protein 70 (Hsp70), Bag-4, and Hsp40: protection against radiation-induced effects and target structure for natural killer cells. Cell Death Differ 12:38–51

    Article  PubMed  CAS  Google Scholar 

  • Gerber DA, Souquere-Besse S, Puvion F, Dubois MF, Bensaude O, Cochet C (2000) Heatinduced relocalization of protein kinase CK2. Implication ofCK2in the context of cellular stress. J Biol Chem 275:23919–23926

    PubMed  CAS  Google Scholar 

  • Gerner EW, Schneider MJ (1975) Induced thermal resistance in HeLa cells. Nature 256:500–502

    Article  PubMed  CAS  Google Scholar 

  • Glover JR, Lindquist S (1998) Hsp104, Hsp70, and Hsp40: a novel chaperone system that rescues previously aggregated proteins. Cell 94:73–82

    Article  PubMed  CAS  Google Scholar 

  • Greene LE, Zinner R, Naficy S, Eisenberg E (1995) Effect of nucleotide on the binding of peptides to 70-kDa heat shock protein. J Biol Chem 270:2967–2973

    Article  PubMed  CAS  Google Scholar 

  • Greene MK, Maskos K, Landry SJ (1998) Role of the J-domain in the cooperation of Hsp40 with Hsp70. Proc Natl Acad Sci U S A 95:6108–6113

    PubMed  CAS  Google Scholar 

  • Ha JH, Hellman U, Johnson ER, Li LS, Mckay DB, Sousa MC, Takeda S, Wernstedt C, Wilbanks SM (1997) Destabilization of peptide binding and interdomain communication by an E543K mutation in the bovine 70-kDa heat shock cognate protein, a molecular chaperone. J Biol Chem 272:27796–27803

    Article  PubMed  CAS  Google Scholar 

  • Hahn GM, Li GC (1982) Thermotolerance and heat shock proteins in mammalian cells. Radiat Res 92:452–457

    PubMed  CAS  Google Scholar 

  • Hartson-Eaton M, Malcolm AW, Hahn GM (1984) Radiosensitivity and thermosensitization of thermotolerant Chinese hamster cells and RIF-1 tumors. Radiat Res 99:175–184

    PubMed  CAS  Google Scholar 

  • Hata M, Okumura K, Seto M, Ohtsuka K (1996) Genomic cloning of a human heat shock protein 40 (Hsp40) gene (HSPF1) and its chromosomal localization to 19p13.2. Genomics 38:446–449

    Article  PubMed  CAS  Google Scholar 

  • Hatayama T, Yasuda K (1998) Association of HSP105 with HSC70 in high molecular mass complexes in mouse FM3A cells. Biochem Biophys Res Commun 248:395–401

    Article  PubMed  CAS  Google Scholar 

  • Hattori H, Kaneda T, Lokeshwar B, Laszlo A, Ohtsuka K (1993) A stress-inducible 40 kDa protein (hsp40): purification by modified two-dimensional gel electrophoresis and colocalization with hsc70 (p73) in heat-shocked HeLa cells. J Cell Sci 104:629–638

    PubMed  CAS  Google Scholar 

  • Haveman J, Hart AAM, Wondergem J (1987) Thermal radiosensitization and thermotolerance in cultured cells from a murine mammary carcinoma. Int J Radiat Biol 51:71–80

    CAS  Google Scholar 

  • Hayes SA, Dice JF (1996) Roles of molecular chaperones in protein degradation. J Cell Biol 132:255–258

    Article  PubMed  CAS  Google Scholar 

  • Hendrick JP, Hartl F-U (1993) Molecular chaperone functions of heat-shock proteins. Annu Rev Biochem 62: 49–384

    Article  Google Scholar 

  • Hohfeld J (1998) Regulation of the heat shock cognate Hsc70 in the mammalian cell: the characterization of the anti-apoptotic protein BAG-1 provides novel insights. Biol Chem 379:269–274

    PubMed  CAS  Google Scholar 

  • Hohfeld J, Jentsch S (1997) GrpE-like regulationof the Hsc70 chaperone by the anti-apoptotic protein BAG-1. EMBO J 16:6209–6216

    Article  PubMed  CAS  Google Scholar 

  • Hohfeld J, Minami Y, Hartl FU (1995) Hip, a novel cochaperone involved in the eukaryotic Hsc70/Hsp40 reaction cycle. Cell 83:589–598

    PubMed  CAS  Google Scholar 

  • Holmberg CI, Staniszewski KE, Mensah KN, Matouschek A, Morimoto RI (2004) Inefficient degradation of truncated polyglutamine proteins by the proteasome. EMBO J 23:4307–4318

    Article  PubMed  CAS  Google Scholar 

  • Horwitz J (1992) a-Crystallin can function as a molecular chaperone. Proc Natl Acad Sci U S A 89: 10449–10453

    PubMed  CAS  Google Scholar 

  • Hut HMJ, Kampinga HH, Sibon OCM (2005) Hsp70 protects mitotic cells against heatinduced centrosome damage and division abnormalities. Mol Biol Cell (in press)

    Google Scholar 

  • Hutchison KA, Dittmar KD, Stancato LF, Pratt WB (1996) Ability of various members of the hsp70 family of chaperones to promote assembly of the glucocorticoid receptor into a functional heterocomplex with hsp90. J. Steroid Biochem Mol Biol 58:251–258

    Article  PubMed  CAS  Google Scholar 

  • Irmer H, Hohfeld J (1997) Characterization of functional domains of the eukaryotic cochaperon Hip. J Biol Chem 272:2230–2235

    PubMed  CAS  Google Scholar 

  • Ishihara K, Yamagishi N, Hatayama T (2003) Protein kinase CK2 phosphorylates Hsp105 alpha at Ser509 and modulates its function. Biochem J 371:917–925

    Article  PubMed  CAS  Google Scholar 

  • Itoh T, Matsuda H, Mori H (1999) Phylogenetic analysis of the third Hsp70 homolog in Escherichia coli: a novel member of the Hsc66 subfamily and its possible co-chaperone. DNA Res 6:299–305

    PubMed  CAS  Google Scholar 

  • Jaattela M (1995) Over-expression of hsp70 confers tumorigenicity to mouse fibrosarcoma cells. Int J Cancer 60:689–693

    PubMed  CAS  Google Scholar 

  • Jaattela M (1999) Escaping cell death: survival proteins in cancer. Exp Cell Res 248:30–43

    Article  PubMed  CAS  Google Scholar 

  • Jaattela M, Wissing D, Kokholm K, Kallunki T, Egeblad M (1998) Hsp70 exerts its antiapoptotic function downstream of caspase-3-like proteases. EMBO J 17:6124–6134

    PubMed  CAS  Google Scholar 

  • Jaenicke R (1991) Protein stability and protein folding. Ciba Found Symp 161:206–216

    PubMed  CAS  Google Scholar 

  • Jakob U, Gaestel M, Engel K, Buchner J (1993) Small heat shock proteins are molecular chaperones. J Biol Chem 268:1517–1520

    PubMed  CAS  Google Scholar 

  • Jiang J, Ballinger CA, Wu Y, Dai Q, Cyr DM, Hohfeld J, Patterson C (2001) CHIP is a U-boxdependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation. J Bio Chem. 276:42938–42944

    CAS  Google Scholar 

  • Johnson BD, Schumacher RJ, Ross ED, Toft DO (1998) Hopmodulates hsp70/hsp90 interactions in protein folding. J Biol Chem 273:3679–3686

    PubMed  CAS  Google Scholar 

  • Johnston JA, Ward CL, Kopito RR (1998) Aggresomes: a cellular response to misfolded proteins. J Cell Biol 143:1883–1898

    Article  PubMed  CAS  Google Scholar 

  • Johnston JA, Illing ME, Kopito RR (2002) Cytoplasmic dynein/dynactin mediates the assembly of aggresomes. Cell Motil Cytoskel 53:26–38

    CAS  Google Scholar 

  • Jorritsma JBM, Burgman P, Kampinga HH, Konings AWT (1986) DNA polymerase activity in heat killing and hyperthermic radiosensitization of mammalian cells as observed after fractionated heat treatments. Radiat Res 105:307–319

    PubMed  CAS  Google Scholar 

  • Kampinga HH (1993) Thermotolerance in mammalian cells. Protein denaturation and aggregation, and stress proteins. J Cell Sci 104:11–17

    PubMed  CAS  Google Scholar 

  • Kampinga HH, Jorritsma JBM, Konings AWT (1985) Heat-induced alterations in DNA polymerase activity of HeLa cells and of isolated nuclei. Relation to cell survival. Int J Radiat Biol 47:29–40

    CAS  Google Scholar 

  • Kampinga HH, Turkel-Uygur N, Roti Roti JL, Konings AW (1989) The relationship of increased nuclear protein content induced by hyperthermia to killing of HeLa S3 cells. Radiat Res 117:511–522

    PubMed  CAS  Google Scholar 

  • Kampinga HH, Brunsting JF, Stege GJJ, Konings AWT, Landry J (1994) Cells overexpressing Hsp27 show accelerated recovery from heat-induced nuclear protein aggregation. Biochem Biophys Res Comm 204:1170–1177

    Article  PubMed  CAS  Google Scholar 

  • Kampinga HH, Konings AW, Evers AJ, Brunsting JF, Misfud N, Anderson RL (1997) Resistance to heat radiosensitization and protein damage in thermotolerant and thermoresistant cells. Int J Radiat Biol 71: 315–326

    PubMed  CAS  Google Scholar 

  • Kampinga HH, Kanon B, Salomons FA, Kabakov AE, Patterson C (2003) Overexpression of the cochaperone CHIP enhances Hsp70-dependent folding activity in mammalian cells. Mol Cell Biol 23:4948–4958

    Article  PubMed  CAS  Google Scholar 

  • Kabani M, McLellan C, Raynes DA, Guerriero V, Brodsky JL (2002) HspBP1, a homologue of the yeast Fes1 and Sls1 proteins, is an Hsc70 nucleotide exchange factor. FEBS Lett 531:339–342

    Article  PubMed  CAS  Google Scholar 

  • Kelley WL (1998) The J-domain family and the recruitment of chaperone power. Trends Biochem Sci 23: 222–227

    Article  PubMed  CAS  Google Scholar 

  • Kelley WL, Georgopoulos C (1997) The T/t common exon of simian virus 40, JC, and BK polyomavirus T antigens can functionally replace the J-domain of the Escherichia coli DnaJ molecular chaperone. Proc Natl Aad Sci U S A 94: 3679–3684

    CAS  Google Scholar 

  • Kim HJ, Song EJ, Lee YS, Kim E, Lee KJ (2005) Human Fas associated factor 1 interacts with heat shock protein 70 and negatively regulates chaperone activity. J Biol Chem 280:8125–8133

    PubMed  CAS  Google Scholar 

  • Kim S, Nollen EA, Kitagawa K, Bindokas VP, Morimoto RI (2002) Polyglutamine protein aggregates are dynamic. Nature Cell Biol 4:826–831

    Article  PubMed  CAS  Google Scholar 

  • King FW, Wawrzynow A, Hohfeld J, Zylicz M (2001) Co-chaperones Bag-1, Hop and Hsp40 regulate Hsc70 and Hsp90 interactions with wild-type or mutant p53. EMBO J 20:6297–6305

    PubMed  CAS  Google Scholar 

  • Knauf U, Jakob U, Engel K, Buchner J, Gaestel M (1994) Stress-and mitogen-induced phosphorylation of the small heat shock protein Hsp25 by MAPKAP kinase 2 is not essential for chaperone properties and cellular thermoresistance. EMBO J 13:54–60

    PubMed  CAS  Google Scholar 

  • Kopito RR (1999) Biosynthesis and degradation of CFTR. Physiol Rev 79: S167–S173

    PubMed  CAS  Google Scholar 

  • Landry J, Chretien P, Lambert H, Hickey E, Weber LA (1989) Heat shock resistance conferred by expression of the human hsp27 gene in rodent cells. J Cell Biol 109:7–15

    Article  PubMed  CAS  Google Scholar 

  • Lange BM, Bachi A, Wilm M, Gonzalez C (2000) Hsp90 is a core centrosomal component and is required at different stages of the centrosome cycle in Drosophila and vertebrates. EMBO J 19:1252–1262

    Article  PubMed  CAS  Google Scholar 

  • Lassle M, Blatch GL, Kundra V, Takatori T, Zetter BR (1997) Stress-inducible, murine protein mSTI1-characterization of binding domains for heat shock proteins and in vitro phosphorylation by different kinases. J Biol Chem 272:1876–1884

    PubMed  CAS  Google Scholar 

  • Laszlo A (1992a) The effects of hyperthermia on mammalian cell structure and function. Cell Prolif 25: 59–87

    PubMed  CAS  Google Scholar 

  • Laszlo A (1992b) The thermoresistant state: protection frominitial damage or better repair? Exp Cell Res 202:519–531

    Article  PubMed  CAS  Google Scholar 

  • Laszlo A, Li GC (1985) Heat-resistant variants of Chinese hamster fibroblasts altered in expression of heat shock protein. Proc Natl Acad Sci U S A 82:8029–8033

    PubMed  CAS  Google Scholar 

  • Lavoie JN, Hickey E, Weber LA, Landry J (1993) Modulation of actinmicrofilament dynamics and fluid phase pinocytosis by phosphorylation of heat shock protein 27. J Biol Chem 268:24210–24214

    PubMed  CAS  Google Scholar 

  • Lavoie JN, Lambert H, Hickey E, Weber LA, Landry J (1995) Modulationof cellular thermoresistance and actin filament stability accompanies phosphorylation-induced changes in the oligomeric structure of heat shock protein 27. Mol Cell Biol 15:505–516

    PubMed  CAS  Google Scholar 

  • Lee SJ, Choi SA, Lee KH, Chung HY, Kim TH, Cho CK, Lee YS (2001) Role of inducible heat shock protein 70 in radiation-induced cell death. Cell Stress Chaperones. 6:273–281

    Article  PubMed  CAS  Google Scholar 

  • Leeyoon D, Easton D, Murawski M, Burd R, Subjeck JR (1995) Identification of a major subfamily of large hsp70-like proteins through the cloning of the mammalian 110-kDa heat shock protein. J Biol Chem 270:15725–15733

    CAS  Google Scholar 

  • Lepock JR, Frey HE, Inniss WE (1990) Thermal analysis of bacteria by differential scanning calorimetry: relationship of protein denaturation in situ to maximum growth temperature. Biochim Biophys Acta 1055:19–26

    PubMed  CAS  Google Scholar 

  • Lepock JR, Frey HE, Ritchie KP (1993) Protein denaturation in intact hepatocytes and isolated cellular organelles during heat shock. J Cell Biol 122:1267–1276

    Article  PubMed  CAS  Google Scholar 

  • Lepock JR, Frey HE, Heynen ML, Senisterra GA, Warters RL (2001) The nuclear matrix is a thermolabile cellular structure. Cell Stress Chaperones. 6:136–147

    Article  PubMed  CAS  Google Scholar 

  • Li GC, Werb Z (1982) Correlation between synthesis of heat shock proteins and development of thermotolerance in Chinese hamster fibro blasts. Proc Natl Acad Sci U S A 79:3218–3222

    PubMed  CAS  Google Scholar 

  • Li GC, Li L, Liu Y-K, Mak JY, Chen L, Lee WMF (1991) Thermal response of rat fibroblasts stably transfected with the human 70-kDa heat shock protein-encoding gene. Proc Natl Acad Sci U S A 88:1681–1685

    PubMed  CAS  Google Scholar 

  • Li GC, Mivechi NF, Weitzel G (1995) Heat shock proteins, thermotolerance, and their relevance to clinical hyperthermia. Int J Hyperthermia 11:459–488

    PubMed  CAS  Google Scholar 

  • Liberek K, Marszalek J, Ang D, Georgopoulos C, Zylicz M (1991) Escherichia coli DnaJ and GrpE heat shock proteins jointly stimulate ATPase activity of DnaK. Proc Natl Acad Sci U S A 88:2874–2878

    PubMed  CAS  Google Scholar 

  • Liberek K, Wall D, Georgopoulos C (1995) The DnaJ chaperone catalytically activates the DnaK chaperone to preferentially bind the sigma(32) heat shock transcriptional regulator. Proc Natl Acad Sci U S A 92: 6224–6228

    PubMed  CAS  Google Scholar 

  • Lindquist S, Craig EA (1988) The heat-shock proteins. Annual Rev Genet 22:631–677

    Article  CAS  Google Scholar 

  • Liu QL, Kishi H, Ohtsuka K, Muraguchi A (2003) Heat shock protein 70 binds caspaseactivated DNase and enhances its activity in TCR-stimulated T cells. Blood 102:1788–1796

    PubMed  CAS  Google Scholar 

  • Loktionova SA, Ilyinskaya OP, Gabai VL, Kabakov AE (1996) Distinct effects of heat shock and ATP depletion on distribution and isoformpatterns of human Hsp27 in endothelial cells. FEBS Lett 392:100–104

    Article  PubMed  CAS  Google Scholar 

  • Luders J, Demand J, Schonfelder S, Frien M, Zimmermann R, Hohfeld J (1998) Cofactorinduced modulation of the functional specificity of the molecular chaperone Hsc70s. Biol Chem 379:1217–1226

    PubMed  CAS  Google Scholar 

  • Martin H, Bruecher J, Claude R, Hoelzer D (1993) Cumulative chemotherapy increases mafosfamide toxicity for normal progenitor cells in aml patients-rationale for cryopreserving adapted-dose purged marrow early in first complete remission. BoneMarrow Transplant 12:495–499

    CAS  Google Scholar 

  • Meacham GC, Patterson C, Zhang W, Younger JM, Cyr DM (2001) The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradation. Nat Cell Biol 3:100–105

    PubMed  CAS  Google Scholar 

  • Melcher A, Todryk S, Hardwick N, Ford M, Jacobson M, Vile RG (1998) Tumor immunogenicity is determined by the mechanism of cell death via induction of heat shock protein expression. Nat Med 4:581–587

    Article  PubMed  CAS  Google Scholar 

  • Merck KB, Groenen PJTA, Voorter CEM, de Haard-Hoekman WA, Horwitz J, Bloemendal H, De Jong WW (1993) Structural and functional similarities of bovine alpha-crystallin and mouse small heat-shock protein. J Biol Chem 268:1046–1052

    PubMed  CAS  Google Scholar 

  • Michels AA, Nguyen VT, Konings AW, Kampinga HH, Bensaude O (1995) Thermostability of a nuclear-targeted luciferase expressed in mammalian cells-destabilizing influence of the intranuclear microenvironment. Eur J Biochem 234: 382–389

    Article  PubMed  CAS  Google Scholar 

  • Michels AA, Kanon B, Konings AW, Ohtsuka K, Bensaude O, Kampinga HH (1997) Hsp70 and Hsp40 chaperone activities in the cytoplasm and the nucleus of mammalian cells. J Biol Chem 272:33283–33289

    PubMed  CAS  Google Scholar 

  • Michels AA, Kanon B, Bensaude O, Kampinga HH (1999) Heat shock protein (Hsp) 40 mutants inhibit Hsp70 in mammalian cells. J Biol Chem 274:36757–36763

    Article  PubMed  CAS  Google Scholar 

  • Minami Y, Hohfeld J, Ohtsuka K, Hartl FU (1996) Regulation of the heat-shock protein 70 reaction cycle by the mammalian DnaJ homolog, Hsp40. J Biol Chem 271:19617–19624

    Article  PubMed  CAS  Google Scholar 

  • Mivechi NF, Li GC (1987) Lack of effect of thermotolerance on radiation response and thermal radiosensitization of murine bone marrow progenitors. Cancer Res 47:1538–1541

    PubMed  CAS  Google Scholar 

  • Morimoto RI (1998) Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev 12:3788–3796

    PubMed  CAS  Google Scholar 

  • Mosser DD, Caron AW, Bourget L, Meriin AB, Sherman MY, Morimoto RI, Massie B (2000) The chaperone function of hsp70 is required for protection against stress-induced apoptosis. Mol Cell Biol 20:7146–7159

    Article  PubMed  CAS  Google Scholar 

  • Mosser DD, Ho S, Glover JR (2004) Saccharomyces cerevisiae Hsp104 enhances the chaperone capacity of human cells and inhibits heat stress-induced proapoptotic signaling. Biochemistry 43:8107–8115

    Article  PubMed  CAS  Google Scholar 

  • Multhoff G, Mizzen L, Winchester CC, Milner CM, Wenk S, Eissner G, Kampinga HH, Laumbacher B, Johnson J (1999) Heat shock protein 70 (Hsp70) stimulates proliferation and cytolytic activity of natural killer cells. Exp Hematol 27:1627–1636

    Article  PubMed  CAS  Google Scholar 

  • Nakahata K, Miyakoda M, Suzuki K, Kodama S, Watanabe M (2002) Heat shock induces centrosomal dysfunction, and causes non-apoptotic mitotic catastrophe in human tumour cells. Int J Hyperthermia 18:332–343

    Article  PubMed  CAS  Google Scholar 

  • Nguyen VT, Morange M, Bensaude O (1989) Protein denaturation during heat shock and related stress. Escherichia coli b-galactosidase and photinus pyralis luciferase inactivation in mouse cells. J Biol Chem 264:10487–10492

    PubMed  CAS  Google Scholar 

  • Nicolet CM, Craig EA (1989) Isolation and characterization of STI1, a stress-inducible gene from Saccharomyces cerevisiae. Mol Cell Biol 9:3638–3646

    PubMed  CAS  Google Scholar 

  • Nimmesgern E, Hartl F-U (1993) ATP-dependent protein refolding activity in reticulocyte lysate. Evidence for the participation of different chaperone components. FEBS 331:25–30

    Article  CAS  Google Scholar 

  • Nollen EA, Brunsting JF, Roelofsen H, Weber LA, Kampinga HH (1999) In vivo chaperone activity of heat shock protein 70 and thermotolerance. Mol Cell Biol 19:2069–2079

    PubMed  CAS  Google Scholar 

  • Nollen EA, Brunsting JF, Song J, Kampinga HH, Morimoto RI (2000) Bag1 functions in vivo as a negative regulator of Hsp70 chaperone activity. Mol Cell Biol 20:1083–1088

    Article  PubMed  CAS  Google Scholar 

  • Nollen EA, Kabakov AE, Brunsting JF, Kanon B, Hohfeld J, Kampinga HH (2001a) Modulation of in vivo HSP70 chaperone activity by Hip and Bag-1. J Biol Chem 276:4677–4682

    Article  PubMed  CAS  Google Scholar 

  • Nollen EA, Salomons FA, Brunsting JF, Want JJ, Sibon OC, Kampinga HH (2001b) Dynamic changes in the localization of thermally unfolded nuclear proteins associated with chaperone-dependent protection. Proc Natl Acad Sci U S A 98:12038–12043

    Article  PubMed  CAS  Google Scholar 

  • Nylandsted J, Gyrd-Hansen M, Danielewicz A, Fehrenbacher N, Lademann U, Hoyer-Hansen M, Weber E, Multhoff G, Rohde M, Jaattela M (2004) Heat shock protein 70 promotes cell survival by inhibiting lysosomal membrane permeabilization. J Exp Med 200:425–435

    Article  PubMed  CAS  Google Scholar 

  • Oh HJ, Chen X, Subjeck JR (1997) Hsp110 protects heat-denatured proteins and confers cellular thermoresistance. J Biol Chem 272:31636–31640

    PubMed  CAS  Google Scholar 

  • Ohtsuka K, Hata M (2000) Mammalian HSP40/DNAJ homologs: cloning of novel cDNAs and a proposal for their classification and nomenclature. Cell Stress Chaperones 5:98–112

    Article  PubMed  CAS  Google Scholar 

  • Parcellier A, Schmitt E, Gurbuxani S, Seigneurin-Berny D, Pance A, Chantome A, Plenchette S, Khochbin S, Solary E, Garrido C (2003) HSP27 is a ubiquitin-binding protein involved in I-kappaBalpha proteasomal degradation. Mol Cell Biol 23:5790–5802

    Article  PubMed  CAS  Google Scholar 

  • Parsell DA, Kowal AS, Lindquist S (1994) Saccharomyces cerevisiae hsp104 protein-purification and characterization of ATP-induced structural changes. J Biol Chem 269:4480–4487

    PubMed  CAS  Google Scholar 

  • Pelham HRB (1984) Hsp70 accelerates the recovery of nucleolar morphology after heat shock. EMBO J 3: 3095–3100

    PubMed  CAS  Google Scholar 

  • Pellecchia M, Montgomery DL, Stevens SY, Vander Kooi CW, Feng HP, Gierasch LM, Zuiderweg ERP (2000) Structural insights into substrate binding by the molecular chaperone DnaK. Nat Struct Biol. 7:298–303

    PubMed  CAS  Google Scholar 

  • Prapapanich V, Chen SY, Toran EJ, Rimerman RA, Smith DF (1996) Mutational analysis of the hsp70-interacting protein hip. Mol Cell Biol 16:6200–6207

    PubMed  CAS  Google Scholar 

  • Prapapanich V, Chen SY, Smith DF (1998) Mutation of hip’s carboxy-terminal region inhibits a transitional stage of progesterone receptor assembly. Mol Cell Biol 18:944–952

    PubMed  CAS  Google Scholar 

  • Pratt WB, Dittmar KD (1998) Studies with purified chaperones advance the understanding of the mechanism of glucocorticoid receptor hsp90 heterocomplex assembly. Trends Endocrinol Metab 9:244–252

    CAS  PubMed  Google Scholar 

  • Raaphorst GP, Azzam EI (1983) Thermal radiosensitization in Chinese hamster (V79) and mouse C3H 10T 1/2 cells. The thermotolerance effect. Br J Cancer 48:45–54

    PubMed  CAS  Google Scholar 

  • Ravikumar B, Duden R, Rubinsztein DC (2002) Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy. HumMol Genet 11:1107–1117

    CAS  Google Scholar 

  • Raynes DA, Guerriero V (1998) Inhibition of Hsp70 ATPase activity and protein renaturation by a novel Hsp70-binding protein. J Biol Chem 273:32883–32888

    Article  PubMed  CAS  Google Scholar 

  • Rudiger S, Buchberger A, Bukau B (1997a) Interaction of Hsp70 chaperones with substrates. Nat Struct Biol 4:342–349

    PubMed  CAS  Google Scholar 

  • Rudiger S, Germeroth L, Schneidermergener J, Bukau B (1997b) Substrate specificity of the DnaK chaperone determined by screening cellulose-bound peptide libraries. EMBO J 16:1501–1507

    Article  PubMed  CAS  Google Scholar 

  • Saleh A, Srinivasula SM, Balkir L, Robbins PD, Alnemri ES (2000) Negative regulation of the Apaf-1 apoptosome by Hsp70. Nat Cell Biol 2:476–483

    PubMed  CAS  Google Scholar 

  • Schmid D, Baici A, Gehring H, Christen P (1994) Kinetics of molecular chaperone action. Science 263: 971–973

    PubMed  CAS  Google Scholar 

  • Schneider C, SeppLorenzino L, Nimmesgern E, Ouerfelli O, Danishefsky S, Rosen N, Hartl FU (1996) Pharmacologic shifting of a balance between protein refolding and degradation mediated by Hsp90. Proc Natl Acad Sci U S A 93: 14536–14541

    Article  PubMed  CAS  Google Scholar 

  • Schroder H, Langer T, Hartl FU, Bukau B (1993) DnaK, DnaJ and GrpE form a cellular chaperone machinery capable of repairing heat-induced protein damage. EMBO J 12:4137–4144

    PubMed  CAS  Google Scholar 

  • Schumacher RJ, Hurst R, Sullivan WP, Mcmahon NJ, Toft DO, Matts RL (1994) ATP-dependent chaperoning activity of reticulocyte lysate. J Biol Chem 269:9493–9499

    PubMed  CAS  Google Scholar 

  • Schumacher RJ, Hansen WJ, Freeman BC, Alnemri E, Litwack G, Toft DO (1996) Cooperative action of Hsp70, Hsp90, and DnaJ proteins in protein renaturation. Biochemistry 35:14889–14898

    Article  PubMed  CAS  Google Scholar 

  • Shi Y, Mosser DD, Morimoto RI (1998) Molecular chaperones as HSF1-specific transcriptional repressors. Genes Dev 12:654–666

    PubMed  CAS  Google Scholar 

  • Shomura Y, Dragovic Z, Chang HC, Tzvetkov N, Young JC, Brodsky JL, Guerriero V, Hartl FU, Bracher A (2005) Regulation of Hsp70 function by HspBP1: structural analysis reveals an alternate mechanism for Hsp70 nucleotide exchange. Mol Cell 17:367–379

    Article  PubMed  CAS  Google Scholar 

  • Shyy T, Subjeck JR, Johnson RJ (1983) The effects of heat shock and growth state on the nucleolar localization of hsp 110. J Cell Biol 97:1389–1395

    PubMed  Google Scholar 

  • Skowyra D, Georgopoulos C, Zylicz M (1990) The E. coli dnaK gene product, the hsp70 homolog, can reactivate heat-inactivated RNA polymerase in anATP hydrolysis-dependent manner. Cell 62:939–944

    Article  PubMed  CAS  Google Scholar 

  • Smith DF (1998) Sequence motifs shared between chaperone components participating in the assembly of progesterone receptor complexes. Biol Chem 379:283–288

    Article  PubMed  CAS  Google Scholar 

  • Sondermann H, Scheufler C, Schneider C, Hohfeld J, Hartl FU, Moarefi I (2001) Structure of a Bag/Hsc70 complex: convergent functional evolution of Hsp70 nucleotide exchange factors. Science 291:1553–1557

    Article  PubMed  CAS  Google Scholar 

  • Song J, Takeda M, Morimoto RI (2001) Bag1-Hsp70 mediates a physiological stress signalling pathway that regulates Raf-1/ERK and cell growth. Nat Cell Biol 3:276–282

    Article  PubMed  CAS  Google Scholar 

  • Spiro IJ, Denman DL, Dewey WC (1982) Effect of hyperthermia on CHO DNA polymerases a and β. Radiat Res 89:134–149

    PubMed  CAS  Google Scholar 

  • Steel R, Doherty JP, Buzzard K, Clemons N, Hawkins CJ, Anderson RL (2004) Hsp72 inhibits apoptosis upstream of the mitochondria and not through interactions with Apaf-1. J Biol Chem 279:51490–51499

    Article  PubMed  CAS  Google Scholar 

  • Stege GJ, Li GC, Li L, Kampinga HH, Konings AW (1994a) On the role of hsp72 in heatinduced intranuclear protein aggregation. Int J Hyperthermia 10:659–674

    PubMed  CAS  Google Scholar 

  • Stege GJ, Li L, Kampinga HH, Konings AW, Li GC (1994b) Importance of the ATP-binding domain and nucleolar localization domain of HSP72 in the protection of nuclear proteins against heat-induced aggregation. Exp Cell Res 214:279–284

    Article  PubMed  CAS  Google Scholar 

  • Stege GJ, Kampinga HH, Konings AW (1995) Heat-induced intranuclear protein aggregation and thermal radiosensitization. Int J Radiat Biol 67:203–209

    PubMed  CAS  Google Scholar 

  • Sturzbecher HW, Chumakov P, Welch WJ, Jenkins JR (1987) Mutant P53 proteins bind Hsp 72/73 cellular heat shock-related proteins in Sv40-transformed monkey cells. Oncogene 1:201–211

    PubMed  CAS  Google Scholar 

  • Suh WC, Burkholder WF, Lu CZ, Zhao X, Gottesman ME, Gross CA (1998) Interaction of the Hsp70 molecular chaperone, DnaK, with its cochaperone DnaJ. Proc Natl Acad Sci U S A 95:15223–15228

    Article  PubMed  CAS  Google Scholar 

  • Szabo A, Korszun R, Hartl FU, Flanagan J (1996) A zinc finger-like domain of the molecular chaperone DnaJ is involved in binding to denatured protein substrates. EMBO J 15:408–417

    PubMed  CAS  Google Scholar 

  • Takayama S, Sato T, Krajewski S, Kochel K, Irie S, Millan JA, Reed JC (1995) Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein with anti-cell death activity. Cell 80:279–284

    Article  PubMed  CAS  Google Scholar 

  • Takayama S, Bimston DN, Matsuzawa S, Freeman BC, Aimesempe C, Xie ZH, Morimoto RI, Reed JC (1997) BAG-1 modulates the chaperone activity of Hsp70/Hsc70. EMBO J 16:4887–4896

    Article  PubMed  CAS  Google Scholar 

  • Takayama S, Xie ZH, Reed JC (1999) An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators. J Biol Chem 274:781–786

    PubMed  CAS  Google Scholar 

  • Takeda S, Mckay DB (1996) Kinetics of peptide binding to the bovine 70 kDa heat shock cognate protein, a molecular chaperone. Biochemistry 35:4636–4644

    Article  PubMed  CAS  Google Scholar 

  • Tavaria M, Gabriele T, Kola I, Anderson RL (1996) A hitchhiker’s guide to the human Hsp70 family. Cell Stress Chaperones. 1:23–28

    Article  PubMed  CAS  Google Scholar 

  • Terada K, Ohtsuka K, Imamoto N, Yoneda Y, Mori M (1995) Role of heat shock cognate 70 protein in import of ornithine transcarbamylase precursor into mammalian mitochondria. Mol Cell Biol 15:3708–3713

    PubMed  CAS  Google Scholar 

  • Thress K, Song J, Morimoto RI, Kornbluth S (2001) Reversible inhibition of Hsp70 chaperone function by Scythe and Reaper. EMBO J 20:1033–1041

    Article  PubMed  CAS  Google Scholar 

  • Todryk S, Melcher AA, Hardwick N, Linardakis E, Bateman A, Colombo MP, Stoppacciaro A, Vile RG (1999) Heat shock protein 70 induced during tumor cell killing induces Th1 cytokines and targets immature dendritic cell precursors to enhance antigen uptake. J Immunol 163:1398–1408

    PubMed  CAS  Google Scholar 

  • Ungewickell E, Ungewickell H, Holstein SEH (1997) Functional interaction of the auxilin J domain with the nucleotide-and substrate-binding modules of Hsc70. Biol. Chem 272:19594–19600

    CAS  Google Scholar 

  • Van de Klundert FAJM, Gijsen MLJ, Van den IJssel PRLA, Snoeckx LHEH, De Jong WW (1998) alpha B-crystallin and hsp25 in neonatal cardiac cells-differences in cellular localization under stress conditions. Eur J Cell Biol 75:38–45

    PubMed  Google Scholar 

  • Vidair CA, Doxsey SJ, Dewey WC (1995) Thermotolerant cells possess an enhanced capacity to repair heat-induced alterations to centrosome structure and function. J Cell Physiol 163:194–203

    Article  PubMed  CAS  Google Scholar 

  • Vidair CA, Huang RN, Doxsey SJ (1996) Heat shock causes protein aggregation and reduced protein solubility at the centrosome and other cytoplasmic locations. Int J Hyperthermia. 12:681–695

    PubMed  CAS  Google Scholar 

  • Volloch VZ, Sherman MY (1999) Oncogenic potential of Hsp72. Oncogene 18:3648–3651

    Article  PubMed  CAS  Google Scholar 

  • Wall D, Zylicz M, Georgopoulos C (1994) The NH2-terminal 108 amino acids of the Escherichia Coli Dnaj protein stimulate the ATPase activity of Dnak and are sufficient for lambda replication. J Biol Chem 269:5446–5451

    PubMed  CAS  Google Scholar 

  • Wall D, Zylicz M, Georgopoulos C (1995) The conserved G/F motif of the DnaJ chaperone is necessary for the activation of the substrate binding properties of the DnaK chaperone. J Biol Chem 270:2139–2144

    PubMed  CAS  Google Scholar 

  • Wang HG, Takayama S, Rapp UR, Reed JC (1996) Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1. Proc Natl Acad Sci U S A 93:7063–7068

    PubMed  CAS  Google Scholar 

  • Warters RL, Stone OL (1983) The effects of hyperthermia on DNA replication in HeLa cells. Radiat Res 93: 71–84

    PubMed  CAS  Google Scholar 

  • Wawrzynow A, Banecki B, Wall D, Liberek K, Georgopoulos C, Zylicz M (1995) ATP hydrolysis is required for the DnaJ-dependent activation of DnaK chaperone for binding to both native and denatured protein substrates. J Biol Chem 270:19307–19311

    PubMed  CAS  Google Scholar 

  • Welch WJ, Suhan JP (1985) Morphological study of the mammalian stress response: characterization of changes in cytoplasmic organelles, cytoskeleton, and nucleoli, and appearance of intranuclear actin filaments in rat fibroblasts after heat-shock treatment. J Cell Biol 101:1198–1211

    Article  PubMed  CAS  Google Scholar 

  • Welch WJ, Suhan JP (1986) Cellular and biochemical events in mammalian cells during and after recovery from physiological stress. J Cell Biol 103:2035–2052

    Article  PubMed  CAS  Google Scholar 

  • Wiech H, Buchner J, Zimmermann R, Jakob U (1992) Hsp90 chaperones protein folding in vitro. Nature 358: 169–170

    Article  PubMed  CAS  Google Scholar 

  • Wyttenbach A, Swartz J, Kita H, Thykjaer T, Carmichael J, Bradley J, Brown R, Maxwell M, Schapira A, Orntoft TF, Kato K, Rubinsztein DC (2001) Polyglutamine expansions cause decreased CRE-mediated transcription and early gene expression changes prior to cell death in an inducible cell model of Huntington’s disease. Hum Mol Genet 10:1829–1845

    Article  PubMed  CAS  Google Scholar 

  • Yamagishi N, Ishihara K, Hatayama T (2004) Hsp105alpha suppresses Hsc70 chaperone activity by inhibiting Hsc70 ATPase activity. J Biol Chem 279:41727–41733

    PubMed  CAS  Google Scholar 

  • Yang XL, Chernenko G, Hao YW, Ding ZH, Pater MM, Pater A, Tang SC (1998) Human BAG-1/RAP46 protein is generated as four isoforms by alternative translation initiation and overexpressed in cancer cells. Oncogene 17: 981–989

    Article  PubMed  CAS  Google Scholar 

  • Yasuda K, Nakai A, Hatayama T, Nagata K (1995) Cloning and expression of murine high molecular mass heat shock proteins, HSP105. J Biol Chem 270:29718–29723

    PubMed  CAS  Google Scholar 

  • Zeiner M, Gebauer M, Gehring U (1997) Mammalian protein RAP46: an interaction partner and modulator of 70 kDa heat shock proteins. EMBO J 16:5483–5490

    Article  PubMed  CAS  Google Scholar 

  • Zeiner M, Gehring U (1995) A protein that interacts with members of the nuclear hormone receptor family: identification and cDNA cloning. Proc Natl Acad Sci U S A 92:11465–11469

    PubMed  CAS  Google Scholar 

  • Zhu XT, Zhao X, Burkholder WF, Gragerov A, Ogata CM, Gottesman ME, Hendrickson WA (1996) Structural analysisof substrate bindingby the molecular chaperone DnaK. Science 272:1606–1614

    PubMed  CAS  Google Scholar 

  • Zylicz M, Ang D, Liberek K, Georgopoulos C (1989) Initiation of lambda-Dna replication with purified host-encoded and bacteriophage-encoded proteins-the role of the Dnak, Dnaj and Grpe heat-shock proteins. EMBO J 8: 1601–1608

    PubMed  CAS  Google Scholar 

  • Zylicz M, King FW, Wawrzynow A (2001) Hsp70 interactions with the p53 tumour suppressor protein. EMBO J 20:4634–4638

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cell Biology, Section of Radiation and Stress Cell Biology, Faculty of Medical Sciences, University of Groningen, Ant. Deusinglaan 1, 9713, AV Groningen, The Netherlands

    H.H. Kampinga

Authors
  1. H.H. Kampinga
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Freiburg i.

    K. Starke

  2. Medical School Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Matthias Gaestel (Professor) (Professor)

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Kampinga, H. (2006). Chaperones in Preventing Protein Denaturation in Living Cells and Protecting Against Cellular Stress. In: Starke, K., Gaestel, M. (eds) Molecular Chaperones in Health and Disease. Handbook of Experimental Pharmacology, vol 172. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-29717-0_1

Download citation

Publish with us

Policies and ethics

Search

Navigation