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Extracellular Hsp90 Governs Spatio-Temporal Regulation of Biological Responses

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Chaperokine Activity of Heat Shock Proteins

Part of the book series: Heat Shock Proteins ((HESP,volume 16))

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Abstract

Heat shock protein (HSP) plays a pivotal role in the maintenance of cellular homeostasis within cells. However, recent studies have unveiled unexpected roles of extracellular HSP in various types of biological responses. For example, extracellular Hsp90 facilitates wound healing via recruiting skin cells. In the field of immunology, it has been shown that the historically important and widely studied extracellular HSP-antigenic peptide complex (HSP-PC) activates adaptive immunity through antigen cross-presentation by professional antigen-presenting cells (pAPCs). In addition, extracellular HSP activates innate immunity as a chaperokine and play a role in the etiology of autoimmune diseases including systemic lupus erythematosus. Therefore, the role of extracellular HSP in immunity is now gaining much attention. The most prominent feature of extracellular HSP in immunity is that they function both on their own and as an HSP-ligand complex such as HSP-antigen peptide complex and HSP-nucleic acid complex. Herein, recapitulating the history, we introduce a unique feature of extracellular HSP as a chaperokine: targeting chaperoned molecules into a particular compartment of dendritic cells and thereby inducing innate immune responses via spatiotemporal regulation. Furthermore, we discuss how such chaperokine activity of extracellular HSP impacts the pathogenesis of autoimmune disease and point out that targeting HSP might be an effective therapeutic approach.

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Abbreviations

APC:

Antigen-presenting cell

CpG:

Cytosine-phosphate- guanine

DC:

Dendritic cell

HIF:

Hypoxia-inducible factor

HSP:

Heat shock protein

Hsp72:

Heat shock protein 72

Hsp90:

Heat shock protein 90

IFN:

Interferon

MVB:

Multivesicular body

SLE:

Systemic lupus erythematosus

TGF-β:

Tumor growth factor-β

TLR:

Toll-like receptor

TNF:

Tumor necrosis factor

References

  • Agrawal H, Jacob N, Carreras E, Bajana S, Putterman C, Turner S, Neas B, Mathian A, Koss MN, Stohl W, Kovats S, Jacob CO (2009) Deficiency of type I IFN receptor in lupus-prone New Zealand mixed 2328 mice decreases dendritic cell numbers and activation and protects from disease. J Immunol 183:6021–6029

    Article  CAS  Google Scholar 

  • Akner G, Mossberg K, Sundqvist KG, Gustafsson JA, Wikstrom AC (1992) Evidence for reversible, non-microtubule and non-microfilament-dependent nuclear translocation of hsp90 after heat shock in human fibroblasts. Eur J Cell Biol 58:356–364

    CAS  PubMed  Google Scholar 

  • Asea A (2005) Stress proteins and initiation of immune response: chaperokine activity of hsp72. Exerc Immunol Rev 11:34–45

    PubMed  PubMed Central  Google Scholar 

  • Asea A, Kabingu E, Stevenson MA, Calderwood SK (2000) HSP70 peptidembearing and peptide-negative preparations act as chaperokines. Cell Stress Chaperones 5:425–431

    Article  CAS  Google Scholar 

  • Asea A, Rehli M, Kabingu E, Boch JA, Bare O, Auron PE, Stevenson MA, Calderwood SK (2002) Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J Biol Chem 277:15028–15034

    Article  CAS  Google Scholar 

  • Basu S, Binder RJ, Suto R, Anderson KM, Srivastava PK (2000) Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-kappa B pathway. Int Immunol 12:1539–1546

    Article  CAS  Google Scholar 

  • Basu S, Binder RJ, Ramalingam T, Srivastava PK (2001) CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. Immunity 14:303–313

    Article  CAS  Google Scholar 

  • Bausero MA, Gastpar R, Multhoff G, Asea A (2005) Alternative mechanism by which IFN-gamma enhances tumor recognition: active release of heat shock protein 72. J Immunol 175:2900–2912

    Article  CAS  Google Scholar 

  • Bennett L, Palucka AK, Arce E, Cantrell V, Borvak J, Banchereau J, Pascual V (2003) Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J Exp Med 197:711–723

    Article  CAS  Google Scholar 

  • Berwin B, Hart JP, Rice S, Gass C, Pizzo SV, Post SR, Nicchitta CV (2003) Scavenger receptor-A mediates gp96/GRP94 and calreticulin internalization by antigen-presenting cells. EMBO J 22:6127–6136

    Article  CAS  Google Scholar 

  • Binder R, Han D, Srivastava P (2000) CD91: a receptor for heat shock protein gp96. Nat Immun 1:151–155

    Article  CAS  Google Scholar 

  • Cheng CF, Fan J, Fedesco M, Guan S, Li Y, Bandyopadhyay B, Bright AM, Yerushalmi D, Liang M, Chen M, Han YP, Woodley DT, Li W (2008) Transforming growth factor alpha (TGFalpha)-stimulated secretion of HSP90alpha: using the receptor LRP-1/CD91 to promote human skin cell migration against a TGFbeta-rich environment during wound healing. Mol Cell Biol 28:3344–3358

    Article  CAS  Google Scholar 

  • Cheng CF, Sahu D, Tsen F, Zhao Z, Fan J, Kim R, Wang X, O'Brien K, Li Y, Kuang Y, Chen M, Woodley DT, Li W (2011) A fragment of secreted Hsp90alpha carries properties that enable it to accelerate effectively both acute and diabetic wound healing in mice. J Clin Invest 121:4348–4361

    Article  CAS  Google Scholar 

  • Clayton A, Turkes A, Navabi H, Mason MD, Tabi Z (2005) Induction of heat shock proteins in B-cell exosomes. J Cell Sci 118:3631–3638

    Article  CAS  Google Scholar 

  • Collins CB, Aherne CM, Yeckes A, Pound K, Eltzschig HK, Jedlicka P, de Zoeten EF (2013) Inhibition of N-terminal ATPase on HSP90 attenuates colitis through enhanced Treg function. Mucosal Immunol 6:960–971

    Article  CAS  Google Scholar 

  • Conroy SE, Faulds GB, Williams W, Latchman DS, Isenberg DA (1994) Detection of autoantibodies to the 90 kDa heat shock protein in systemic lupus erythematosus and other autoimmune diseases. Br J Rheumatol 33:923–926

    Article  CAS  Google Scholar 

  • Crow MK (2014) Type I interferon in the pathogenesis of lupus. J Immunol 192:5459–5468

    Article  CAS  Google Scholar 

  • Crow MK, Kirou KA (2004) Interferon-alpha in systemic lupus erythematosus. Curr Opin Rheumatol 16:541–547

    Article  CAS  Google Scholar 

  • Csermely P, Schnaider T, Soti C, Prohaszka Z, Nardai G (1998) The 90-kDa molecular chaperone family: structure, function, and clinical applications. A comprehensive review. Pharmacol Ther 79:129–168

    Article  CAS  Google Scholar 

  • Delneste Y, Magistrelli G, Gauchat J, Haeuw J, Aubry J, Nakamura K, Kawakami-Honda N, Goetsch L, Sawamura T, Bonnefoy J, Jeannin P (2002) Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation. Immunity 17:353–362

    Article  CAS  Google Scholar 

  • Elkon KB, Stone VV (2011) Type I interferon and systemic lupus erythematosus. J Interferon Cytokine Res: Off J Int Soc Interferon Cytokine Res 31:803–812

    Article  CAS  Google Scholar 

  • Eustace BK, Sakurai T, Stewart JK, Yimlamai D, Unger C, Zehetmeier C, Lain B, Torella C, Henning SW, Beste G, Scroggins BT, Neckers L, Ilag LL, Jay DG (2004) Functional proteomic screens reveal an essential extracellular role for hsp90 alpha in cancer cell invasiveness. Nat Cell Biol 6:507–514

    Article  CAS  Google Scholar 

  • Fukui R, Saitoh S, Matsumoto F, Kozuka-Hata H, Oyama M, Tabeta K, Beutler B, Miyake K (2009) Unc93B1 biases Toll-like receptor responses to nucleic acid in dendritic cells toward DNA- but against RNA-sensing. J Exp Med 206:1339–1350

    Article  CAS  Google Scholar 

  • Gastpar R, Gehrmann M, Bausero MA, Asea A, Gross C, Schroeder JA, Multhoff G (2005) Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Cancer Res 65:5238–5247

    Article  CAS  Google Scholar 

  • Guiducci C, Ott G, Chan JH, Damon E, Calacsan C, Matray T, Lee KD, Coffman RL, Barrat FJ (2006) Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9 activation. J Exp Med 203:1999–2008

    Article  CAS  Google Scholar 

  • Hegmans JP, Bard MP, Hemmes A, Luider TM, Kleijmeer MJ, Prins JB, Zitvogel L, Burgers SA, Hoogsteden HC, Lambrecht BN (2004) Proteomic analysis of exosomes secreted by human mesothelioma cells. Am J Pathol 164:1807–1815

    Article  CAS  Google Scholar 

  • Hightower LE, Guidon PT Jr (1989) Selective release from cultured mammalian cells of heat-shock (stress) proteins that resemble glia-axon transfer proteins. J Cell Physiol 138:257–266

    Article  CAS  Google Scholar 

  • Honda K, Ohba Y, Yanai H, Negishi H, Mizutani T, Takaoka A, Taya C, Taniguchi T (2005) Spatiotemporal regulation of MyD88-IRF-7 signalling for robust type-I interferon induction. Nature 434:1035–1040

    Article  CAS  Google Scholar 

  • Jego G, Palucka AK, Blanck JP, Chalouni C, Pascual V, Banchereau J (2003) Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6. Immunity 19:225–234

    Article  CAS  Google Scholar 

  • Krieg A (2002) CpG motifs in bacterial DNA and their immune effects. Annu Rev Immunol 20:709–760

    Article  CAS  Google Scholar 

  • Kurotaki T, Tamura Y, Ueda G, Oura J, Kutomi G, Hirohashi Y, Sahara H, Torigoe T, Hiratsuka H, Sunakawa H, Hirata K, Sato N (2007) Efficient cross-presentation by heat shock protein 90-peptide complex-loaded dendritic cells via an endosomal pathway. J Immunol 179:1803–1813

    Article  CAS  Google Scholar 

  • Lakadamyali M, Rust MJ, Zhuang X (2006) Ligands for clathrin-mediated endocytosis are differentially sorted into distinct populations of early endosomes. Cell 124:997–1009

    Article  CAS  Google Scholar 

  • Lande R, Gregorio J, Facchinetti V, Chatterjee B, Wang YH, Homey B, Cao W, Su B, Nestle FO, Zal T, Mellman I, Schroder JM, Liu YJ, Gilliet M (2007) Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 449:564–569

    Article  CAS  Google Scholar 

  • Li W, Li Y, Guan S, Fan J, Cheng CF, Bright AM, Chinn C, Chen M, Woodley DT (2007) Extracellular heat shock protein-90alpha: linking hypoxia to skin cell motility and wound healing. EMBO J 26:1221–1233

    Article  CAS  Google Scholar 

  • Liao DF, Jin ZG, Baas AS, Daum G, Gygi SP, Aebersold R, Berk BC (2000) Purification and identification of secreted oxidative stress-induced factors from vascular smooth muscle cells. J Biol Chem 275:189–196

    Article  CAS  Google Scholar 

  • Liu Z, Davidson A (2012) Taming lupus-a new understanding of pathogenesis is leading to clinical advances. Nat Med 18:871–882

    Article  Google Scholar 

  • Liu B, Yang Y, Qiu Z, Staron M, Hong F, Li Y, Wu S, Hao B, Bona R, Han D, Li Z (2010) Folding of Toll-like receptors by the HSP90 paralogue gp96 requires a substrate-specific cochaperone. Nat Commun 1:79

    Article  Google Scholar 

  • Minota S, Koyasu S, Yahara I, Winfield J (1988) Autoantibodies to the heat-shock protein hsp90 in systemic lupus erythematosus. J Clin Invest 81:106–109

    Article  CAS  Google Scholar 

  • Multhoff G, Hightower LE (1996) Cell surface expression of heat shock proteins and the immune response. Cell Stress Chaperones 1:167–176

    Article  CAS  Google Scholar 

  • Okuya K, Tamura Y, Saito K, Kutomi G, Torigoe T, Hirata K, Sato N (2010) Spatiotemporal regulation of heat shock protein 90-chaperoned self-DNA and CpG-oligodeoxynucleotide for type I IFN induction via targeting to static early endosome. J Immunol 184:7092–7099

    Article  CAS  Google Scholar 

  • Palladino MA Jr, Srivastava PK, Oettgen HF, DeLeo AB (1987) Expression of a shared tumor-specific antigen by two chemically induced BALB/c sarcomas. Cancer Res 47:5074–5079

    PubMed  Google Scholar 

  • Perry D, Sang A, Yin Y, Zheng YY, Morel L (2011) Murine models of systemic lupus erythematosus. J Biomed Biotechnol 2011:271694

    Article  Google Scholar 

  • Ripley BJ, Isenberg DA, Latchman DS (2001) Elevated levels of the 90 kDa heat shock protein (hsp90) in SLE correlate with levels of IL-6 and autoantibodies to hsp90. J Autoimmun 17:341–346

    Article  CAS  Google Scholar 

  • Ronnblom L, Alm GV, Eloranta ML (2009) Type I interferon and lupus. Curr Opin Rheumatol 21:471–477

    Article  Google Scholar 

  • Sahu D, Zhao Z, Tsen F, Cheng CF, Park R, Situ AJ, Dai J, Eginli A, Shams S, Chen M, Ulmer TS, Conti P, Woodley DT, Li W (2012) A potentially common peptide target in secreted heat shock protein-90alpha for hypoxia-inducible factor-1alpha-positive tumors. Mol Biol Cell 23:602–613

    Article  CAS  Google Scholar 

  • Saito K, Kukita K, Kutomi G, Okuya K, Asanuma H, Tabeya T, Naishiro Y, Yamamoto M, Takahashi H, Torigoe T, Nakai A, Shinomura Y, Hirata K, Sato N, Tamura Y (2015) Heat shock protein 90 associates with Toll-like receptors 7/9 and mediates self-nucleic acid recognition in SLE. Eur J Immunol 45:2028–2041

    Article  CAS  Google Scholar 

  • Sasai M, Linehan MM, Iwasaki A (2010) Bifurcation of Toll-like receptor 9 signaling by adaptor protein 3. Science 329:1530–1534

    Article  CAS  Google Scholar 

  • Semenza GL (2007) Evaluation of HIF-1 inhibitors as anticancer agents. Drug Discov Today 12:853–859

    Article  CAS  Google Scholar 

  • Shimp SK 3rd, Chafin CB, Regna NL, Hammond SE, Read MA, Caudell DL, Rylander M, Reilly CM (2012) Heat shock protein 90 inhibition by 17-DMAG lessens disease in the MRL/lpr mouse model of systemic lupus erythematosus. Cell Mol Immunol 9:255–266

    Article  CAS  Google Scholar 

  • Srivastava P (2002) Interaction of heat shock proteins with peptides and antigen presenting cells: chaperoning of the innate and adaptive immune responses. Annu Rev Immunol 20:395–425

    Article  CAS  Google Scholar 

  • Stocki P, Dickinson AM (2012) The immunosuppressive activity of heat shock protein 70. Autoimmune Dis 2012:617213

    PubMed  PubMed Central  Google Scholar 

  • Suto R, Srivastava PK (1995) A mechanism for the specific immunogenicity of heat shock protein-chaperoned peptides. Science 269:1585–1588

    Article  CAS  Google Scholar 

  • Suzuki S, Kulkarni AB (2010) Extracellular heat shock protein HSP90beta secreted by MG63 osteosarcoma cells inhibits activation of latent TGF-beta1. Biochem Biophys Res Commun 398:525–531

    Article  CAS  Google Scholar 

  • Takahashi K, Shibata T, Akashi-Takamura S, Kiyokawa T, Wakabayashi Y, Tanimura N, Kobayashi T, Matsumoto F, Fukui R, Kouro T, Nagai Y, Takatsu K, Saitoh S, Miyake K (2007) A protein associated with Toll-like receptor (TLR) 4 (PRAT4A) is required for TLR-dependent immune responses. J Exp Med 204:2963–2976

    Article  CAS  Google Scholar 

  • Tamura Y, Peng P, Liu K, Daou M, Srivastava PK (1997) Immunotherapy of tumors with autologous tumor-derived heat shock protein preparations. Science 278:117–120

    Article  CAS  Google Scholar 

  • Tanaka T, Okuya K, Kutomi G, Takaya A, Kajiwara T, Kanaseki T, Tsukahara T, Hirohashi Y, Torigoe T, Hirata K, Okamoto Y, Sato N, Tamura Y (2015) Heat shock protein 90 targets a chaperoned peptide to the static early endosome for efficient cross-presentation by human dendritic cells. Cancer Sci 106:18–24

    Article  CAS  Google Scholar 

  • Trepel J, Mollapour M, Giaccone G, Neckers L (2010) Targeting the dynamic HSP90 complex in cancer. Nat Rev Cancer 10:537–549

    Article  CAS  Google Scholar 

  • Triantafyllopoulou A, Franzke CW, Seshan SV, Perino G, Kalliolias GD, Ramanujam M, van Rooijen N, Davidson A, Ivashkiv LB (2010) Proliferative lesions and metalloproteinase activity in murine lupus nephritis mediated by type I interferons and macrophages. Proc Natl Acad Sci U S A 107:3012–3017

    Article  CAS  Google Scholar 

  • Trinchieri G (2010) Type I interferon: friend or foe? J Exp Med 207:2053–2063

    Article  CAS  Google Scholar 

  • Tsutsumi S, Neckers L (2007) Extracellular heat shock protein 90: a role for a molecular chaperone in cell motility and cancer metastasis. Cancer Sci 98:1536–1539

    Article  CAS  Google Scholar 

  • Tsutsumi S, Mollapour M, Graf C, Lee CT, Scroggins BT, Xu W, Haslerova L, Hessling M, Konstantinova AA, Trepel JB, Panaretou B, Buchner J, Mayer MP, Prodromou C, Neckers L (2009) Hsp90 charged-linker truncation reverses the functional consequences of weakened hydrophobic contacts in the N domain. Nat Struct Mol Biol 16:1141–1147

    Article  CAS  Google Scholar 

  • Tukaj S, Tiburzy B, Manz R, de Castro Marques A, Orosz A, Ludwig RJ, Zillikens D, Kasperkiewicz M (2014) Immunomodulatory effects of heat shock protein 90 inhibition on humoral immune responses. Exp Dermatol 23:585–590

    Article  CAS  Google Scholar 

  • Twomey BM, Dhillon VB, McCallum S, Isenberg DA, Latchman DS (1993) Elevated levels of the 90 kD heat shock protein in patients with systemic lupus erythematosus are dependent upon enhanced transcription of the hsp90 beta gene. J Autoimmun 6:495–506

    Article  CAS  Google Scholar 

  • Udono H, Srivastava PK (1994) Comparison of tumor-specific immunogenicities of stress-induced proteins gp96, hsp90, and hsp70. J Immunol 152:5398–5403

    CAS  PubMed  Google Scholar 

  • Viglianti GA, Lau CM, Hanley TM, Miko BA, Shlomchik MJ, Marshak-Rothstein A (2003) Activation of autoreactive B cells by CpG dsDNA. Immunity 19:837–847

    Article  CAS  Google Scholar 

  • Wagner H (1999) Bacterial CpG DNA activates immune cells to signal infectious danger. Adv Immunol 73:329–368

    Article  CAS  Google Scholar 

  • Wang XY, Facciponte J, Chen X, Subjeck JR, Repasky EA (2007) Scavenger receptor-A negatively regulates antitumor immunity. Cancer Res 67:4996–5002

    Article  CAS  Google Scholar 

  • Wang X, Song X, Zhuo W, Fu Y, Shi H, Liang Y, Tong M, Chang G, Luo Y (2009) The regulatory mechanism of Hsp90alpha secretion and its function in tumor malignancy. Proc Natl Acad Sci U S A 106:21288–21293

    Article  CAS  Google Scholar 

  • Whitesell L, Lindquist SL (2005) HSP90 and the chaperoning of cancer. Nat Rev Cancer 5:761–772

    Article  CAS  Google Scholar 

  • Woodley DT, Fan J, Cheng CF, Li Y, Chen M, Bu G, Li W (2009) Participation of the lipoprotein receptor LRP1 in hypoxia-HSP90alpha autocrine signaling to promote keratinocyte migration. J Cell Sci 122:1495–1498

    Article  CAS  Google Scholar 

  • Yanai H, Ban T, Wang Z, Choi MK, Kawamura T, Negishi H, Nakasato M, Lu Y, Hangai S, Koshiba R, Savitsky D, Ronfani L, Akira S, Bianchi ME, Honda K, Tamura T, Kodama T, Taniguchi T (2009) HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses. Nature 462:99–103

    Article  CAS  Google Scholar 

  • Yang Y, Liu B, Dai J, Srivastava PK, Zammit DJ, Lefrancois L, Li Z (2007) Heat shock protein gp96 is a master chaperone for toll-like receptors and is important in the innate function of macrophages. Immunity 26:215–226

    Article  Google Scholar 

  • Yasuda K, Yu P, Kirschning CJ, Schlatter B, Schmitz F, Heit A, Bauer S, Hochrein H, Wagner H (2005) Endosomal translocation of vertebrate DNA activates dendritic cells via TLR9-dependent and -independent pathways. J Immunol 174:6129–6136

    Article  CAS  Google Scholar 

  • Yoshida H, Okabe Y, Kawane K, Fukuyama H, Nagata S (2005) Lethal anemia caused by interferon-beta produced in mouse embryos carrying undigested DNA. Nat Immunol 6:49–56

    Article  CAS  Google Scholar 

  • Zhang H, Zhang L, Yu F, Liu Y, Liang Q, Deng G, Chen G, Liu M, Xiao X (2012) HSF1 is a transcriptional activator of IL-10 gene expression in RAW264.7 macrophages. Inflammation 35:1558–1566

    Article  CAS  Google Scholar 

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Acknowledgements

This research was partially supported by the Center of Innovation Program from MEXT and JST.

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Authors and Affiliations

  1. Department of Molecular Therapeutics, Center for Food & Medical Innovation, Institute for Innovation and Business Promotion, Hokkaido University, Sapporo, Japan

    Yasuaki Tamura, Akihiro Yoneda, Norio Takei & Kaori Sawada

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  1. Yasuaki Tamura
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  2. Akihiro Yoneda
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  3. Norio Takei
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  4. Kaori Sawada
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Editors and Affiliations

  1. Department of Medicine and Director, Precision Therapeutics Proteogenomics Diagnostic Center, Eleanor N. Dana Cancer Center, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA

    Alexzander A. A. Asea

  2. Department of Experimental Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA

    Punit Kaur

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Tamura, Y., Yoneda, A., Takei, N., Sawada, K. (2019). Extracellular Hsp90 Governs Spatio-Temporal Regulation of Biological Responses. In: Asea, A., Kaur, P. (eds) Chaperokine Activity of Heat Shock Proteins . Heat Shock Proteins, vol 16. Springer, Cham. https://doi.org/10.1007/978-3-030-02254-9_13

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