Abstract
Constitutively expressed small heat shock protein HspB1 regulates many fundamental cellular processes and plays major roles in many human pathological diseases. In that regard, this chaperone has a huge number of apparently unrelated functions that appear linked to its ability to recognize many client polypeptides that are subsequently modified in their activity and/or half-life. A major parameter to understand how HspB1 is dedicated to interact with particular clients in defined cellular conditions relates to its complex oligomerization and phosphorylation properties. Indeed, HspB1 structural organization displays dynamic and complex rearrangements in response to changes in the cellular environment or when the cell physiology is modified. These structural modifications probably reflect the formation of structural platforms aimed at recognizing specific client polypeptides. Here, I have reviewed data from the literature and re-analyzed my own studies to describe and discuss these fascinating changes in HspB1 structural organization.
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References
Acunzo J, Andrieu C, Baylot V, Rocchi P (2014) Hsp27 as a therapeutic target in cancers. Curr Drug Targets 5:423–431
Aloy MT, Hadchity E, Bionda C, Diaz-Latoud C, Claude L, Rousson R, Arrigo A-P, Rodriguez-Lafrasse C (2008) Protective role of Hsp27 protein against gamma radiation-induced apoptosis and radiosensitization effects of Hsp27 gene silencing in different human tumor cells. Int J Radiat Oncol Biol Phys 70:543–553
Arrigo A-P (1990) Tumor necrosis factor induces the rapid phosphorylation of the mammalian heat shock protein hsp28. Mol Cell Biol 10:1276–1280
Arrigo A-P (1998) Small stress proteins: chaperones that act as regulators of intracellular redox state and programmed cell death. Biol Chem 379:19–26
Arrigo A-P (2000) sHsp as novel regulators of programmed cell death and tumorigenicity. Pathol Biol (Paris) 48:280–288
Arrigo A-P (2001) Hsp27: novel regulator of intracellular redox state. IUBMB Life 52:303–307
Arrigo A-P (2005) In search of the molecular mechanism by which small stress proteins counteract apoptosis during cellular differentiation. J Cell Biochem 94:241–246
Arrigo A-P (2007) The cellular “networking” of mammalian Hsp27 and its functions in the control of protein folding, redox state and apoptosis. Adv Exp Med Biol 594:14–26
Arrigo A-P (2011) Structure-functions of HspB1 (Hsp27). Methods Mol Biol 787:105–119
Arrigo A-P (2012) Pathology-dependent effects linked to small heat shock proteins expression. Scientifica 2012:185641. doi:10.6064/2012/185641
Arrigo A-P (2013) Human small heat shock proteins: protein interactomes of homo- and hetero-oligomeric complexes: an update. FEBS Lett 587:1959–1969
Arrigo A-P, Ducarouge B, Lavial F, Gibert B (2015) Immense cellular implications associated to small stress proteins expression: impacts on human pathologies. In: R.M. Tanguay LEH (ed) The big book on small heat shock proteins, pp 27–83. © Springer International Publishing Switzerland 2015
Arrigo A-P, Ducasse C (2002) Expression of the anti-apoptotic protein Hsp27 during both the keratinocyte differentiation and dedifferentiation of HaCat cells: expression linked to changes in intracellular protein organization? Exp Gerontol 37:1247–1255
Arrigo A-P, Firdaus WJ, Mellier G, Moulin M, Paul C, Diaz-Latoud C, Kretz-Remy C (2005a) Cytotoxic effects induced by oxidative stress in cultured mammalian cells and protection provided by Hsp27 expression. Methods 35:126–138
Arrigo A-P, Gibert B (2012) HspB1 dynamic phospho-oligomeric structure dependent interactome as cancer therapeutic target. Curr Mol Med 12:1151–1163
Arrigo A-P, Gibert B (2013) Protein interactomes of three stress inducible small heat shock proteins: HspB1, HspB5 and HspB8. Int J Hyperth 29:409–422
Arrigo A-P, Gibert B (2014) HspB1, HspB5 and HspB4 in human cancers: potent oncogenic role of some of their client proteins. Cancers (Basel) 6:333–365
Arrigo A-P, Simon S, Gibert B, Kretz-Remy C, Nivon M, Czekalla A, Guillet D, Moulin M, Diaz-Latoud C, Vicart P (2007) Hsp27 (HspB1) and alphaB-crystallin (HspB5) as therapeutic targets. FEBS Lett 581:3665–3674
Arrigo A-P, 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
Arrigo A-P, Virot S, Chaufour S, Firdaus W, Kretz-Remy C, Diaz-Latoud C (2005b) Hsp27 consolidates intracellular redox homeostasis by upholding glutathione in its reduced form and by decreasing iron intracellular levels. Antioxid Redox Signal 7:414–422
Arrigo A-P, Welch W (1987) Characterization and purification of the small 28,000-Dalton mammalian heat shock protein. J Biol Chem 262:15359–15369
Baranova EV, Weeks SD, Beelen S, Bukach OV, Gusev NB, Strelkov SV (2011) Three-dimensional structure of alpha-crystallin domain dimers of human small heat shock proteins HSPB1 and HSPB6. J Mol Biol 411:110–122
Basha E, O’Neill H, Vierling E (2011) Small heat shock proteins and alpha-crystallins: dynamic proteins with flexible functions. Trends Biochem Sci 37:106–117
Bausero MA, Bharti A, Page DT, Perez KD, Eng JW, Ordonez SL, Asea EE, Jantschitsch C, Kindas-Muegge I, Ciocca D, Asea A (2006) Silencing the hsp25 gene eliminates migration capability of the highly metastatic murine 4T1 breast adenocarcinoma cell. Tumour Biol 27:17–26
Benndorf R, Martin JL, Kosakovsky Pond SL, Wertheim JO (2014) Neuropathy- and myopathy-associated mutations in human small heat shock proteins: characteristics and evolutionary history of the mutation sites. Mutat Res 6 S1383-5742(14):00018–00010
Boncoraglio A, Minoia M, Carra S (2012) The family of mammalian small heat shock proteins (HSPBs): implications in protein deposit diseases and motor neuropathies. Int J Biochem Cell Biol 44:1657–1669
Bruey JM, Ducasse C, Bonniaud P, Ravagnan L, Susin SA, Diaz-Latoud C, Gurbuxani S, Arrigo A-P, Kroemer G, Solary E, Garrido C (2000a) Hsp27 negatively regulates cell death by interacting with cytochrome c. Nat Cell Biol 2:645–652
Bruey JM, Paul C, Fromentin A, Hilpert S, Arrigo A-P, Solary E, Garrido C (2000b) Differential regulation of Hsp27 oligomerization in tumor cells grown in vitro and in vivo. Oncogene 19:4855–4863
Calderwood SK (2012) HSF1, a versatile factor in tumorogenesis. Curr Mol Med 12:1102–1107
Calderwood SK, Khaleque MA, Sawyer DB, Ciocca DR (2006) Heat shock proteins in cancer: chaperones of tumorigenesis. Trends Biochem Sci 31:164–172
Charette SJ, Lavoie JN, Lambert H, Landry J (2000) Inhibition of Daxx-mediated apoptosis by heat shock protein 27. Mol Cell Biol 20:7602–7612
Chaufour S, Mehlen P, Arrigo A-P (1996) Transient accumulation, phosphorylation and changes in the oligomerization of Hsp27 during retinoic acid-induced differentiation of HL-60 cells: possible role in the control of cellular growth and differentiation. Cell Stress Chaperones 1:225–235
Chen H, Zheng C, Zhang Y, Chang YZ, Qian ZM, Shen X (2006) Heat shock protein 27 downregulates the transferrin receptor 1-mediated iron uptake. Int J Biochem Cell Biol 38:1402–1416
Choi SH, Nam JK, Kim BY, Jang J, Jin YB, Lee HJ, Park S, Ji YH, Cho J, Lee YJ (2016) HSPB1 inhibits the endothelial-to-mesenchymal transition to suppress pulmonary fibrosis and lung tumorigenesis. Cancer Res 76:1019–1030
Ciocca DR, Arrigo A-P, Calderwood SK (2013) Heat shock proteins and heat shock factor 1 in carcinogenesis and tumor development: an update. Arch Toxicol 87:19–48
Ciocca DR, Cappello F, Cuello-Carrion ED, Arrigo A-P (2015) Molecular approaches to target heat shock proteins for cancer treatment. Frontiers in Clinical Drug Research - Anti-Cancer Agents 2:3–47
Concannon CG, Gorman AM, Samali A (2003) On the role of Hsp27 in regulating apoptosis. Apoptosis 8:61–70
Cosentino C, Grieco D, Costanzo V (2011) ATM activates the pentose phosphate pathway promoting anti-oxidant defence and DNA repair. EMBO J 30:546–555
Dalle-Donne I, Rossi R, Milzani A, Di Simplicio P, Colombo R (2001) The actin cytoskeleton response to oxidants: from small heat shock protein phosphorylation to changes in the redox state of actin itself. Free Radic Biol Med 31:1624–1632
Davidson SM, Morange M (2000) Hsp25 and the p38 MAPK pathway are involved in differentiation of cardiomyocytes. Dev Biol 218:146–160
de Thonel A, Vandekerckhove J, Lanneau D, Selvakumar S, Courtois G, Hazoume A, Brunet M, Maurel S, Hammann A, Ribeil JA, Zermati Y, Gabet AS, Boyes J, Solary E, Hermine O, Garrido C (2010) Hsp27 controls GATA-1 protein level during erythroid cell differentiation. Blood 116:85–96
Devaja O, King RJ, Papadopoulos A, Raju KS (1997) Heat-shock protein 27 (Hsp27) and its role in female reproductive organs. Eur J Gynaecol Oncol 18:16–22
Diaz-Latoud C, Buache E, Javouhey E, Arrigo A-P (2005) Substitution of the unique cysteine residue of murine hsp25 interferes with the protective activity of this stress protein through inhibition of dimer formation. Antioxid Redox Signal 7:436–445
Duverger O, Paslaru L, Morange M (2004) HSP25 is involved in two steps of the differentiation of PAM212 keratinocytes. J Biol Chem 279:10252–10260
Ehrnsperger M, Gaestel M, Buchner J (2000) Analysis of chaperone properties of small Hsp’s. Methods Mol Biol 99:421–429
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
Ehrnsperger M, Lilie H, Gaestel M, Buchner J (1999) The dynamics of hsp25 quaternary structure. Structure and function of different oligomeric species. J Biol Chem 274:14867–14874
Fanelli MA, Montt-Guevara M, Diblasi AM, Gago FE, Tello O, Cuello-Carrion FD, Callegari E, Bausero MA, Ciocca DR (2008) P-cadherin and beta-catenin are useful prognostic markers in breast cancer patients; beta-catenin interacts with heat shock protein Hsp27. Cell Stress Chaperones 13:207–220
Favet N, Duverger O, Loones MT, Poliard A, Kellermann O, Morange M (2001) Overexpression of murine small heat shock protein HSP25 interferes with chondrocyte differentiation and decreases cell adhesion. Cell Death Differ 8:603–613
Firdaus WJ, Wyttenbach A, Diaz-Latoud C, Currie RW, Arrigo A-P (2006) Analysis of oxidative events induced by expanded polyglutamine huntingtin exon 1 that are differentially restored by expression of heat shock proteins or treatment with an antioxidant. FEBS J 273:3076–3093
Fossa P, Cichero E (2015) In silico evaluation of human small heat shock protein Hsp27: homology modeling, mutation analyses and docking studies. Bioorg Med Chem 23:3215–3220
Franklin TB, Krueger-Naug AM, Clarke DB, Arrigo A-P, Currie RW (2005) The role of heat shock proteins Hsp70 and Hsp27 in cellular protection of the central nervous system. Int J Hyperth 21:379–392
Gaestel M, Gross B, Benndorf R, Strauss M, Schunk W-H, Kraft R, Otto A, Bohm H, Stahl J, Drabsch H, Bielka H (1989) Molecular cloning, sequencing and expression in Escherichia coli of the 25-kDa growth-related protein of Ehrlich ascites tumor and its homology to mammalian stress proteins. Eur J Biochem 179:209–213
Garrido C (2002) Size matters: of the small Hsp27 and its large oligomers. Cell Death Differ 9:483–485
Garrido C, Bruey JM, Fromentin A, Hammann A, Arrigo A-P, Solary E (1999) Hsp27 inhibits cytochrome c-dependent activation of procaspase-9. FASEB J 13:2061–2070
Garrido C, Brunet M, Didelot C, Zermati Y, Schmitt E, Kroemer G (2006) Heat shock proteins 27 and 70: anti-apoptotic proteins with tumorigenic properties. Cell Cycle 5:22
Garrido C, Fromentin A, Bonnotte B, Favre N, Moutet M, Arrigo A-P, Mehlen P, Solary E (1998) Heat shock protein 27 enhances the tumorigenicity of immunogenic rat colon carcinoma cell clones. Cancer Res 58:5495–5499
Garrido C, Ottavi P, Fromentin A, Hammann A, Arrigo A-P, Chauffert B, Mehlen P (1997) Hsp27 as a mediator of confluence-dependent resistance to cell death induced by anticancer drugs. Cancer Res 57:2661–2667
Gibert B, Eckel B, Fasquelle L, Moulin M, Bouhallier F, Gonin V, Mellier G, Simon S, Kretz-Remy C, Arrigo A-P, Diaz-Latoud C (2012a) Knock down of heat shock protein 27 (HspB1) induces degradation of several putative client proteins. PLoS One 7:e29719
Gibert B, Eckel B, Gonin V, Goldschneider D, Fombonne J, Deux B, Mehlen P, Arrigo A-P, Clezardin P, Diaz-Latoud C (2012b) Targeting heat shock protein 27 (HspB1) interferes with bone metastasis and tumour formation in vivo. Br J Cancer 107:63–70
Hanash S, Strahler J, Chan Y, Kuick R, Teichroew D, Neel J, Hailat N, Keim D, Gratiot-Deans J, Ungar D et al (1993) Data base analysis of protein expression patterns during T-cell ontogeny and activation. Proc Natl Acad Sci U S A 90:3314–3318
Havasi A, Li Z, Wang Z, Martin JL, Botla V, Ruchalski K, Schwartz JH, Borkan SC (2008) Hsp27 inhibits Bax activation and apoptosis via a phosphatidylinositol 3-kinase-dependent mechanism. J Biol Chem 283:12305–12313
Hayashi N, Peacock JW, Beraldi E, Zoubeidi A, Gleave ME, Ong CJ (2012) Hsp27 silencing coordinately inhibits proliferation and promotes Fas-induced apoptosis by regulating the PEA-15 molecular switch. Cell Death Differ 19:990–1002
Hayes D, Napoli V, Mazurkie A, Stafford WF, Graceffa P (2009) Phosphorylation dependence of Hsp27 multimeric size and molecular chaperone function. J Biol Chem 284:18801–18807
Huot J, Houle F, Rousseau S, Deschesnes RG, Shah GM, Landry J (1998) SAPK2/p38-dependent F-actin reorganization regulates early membrane blebbing during stress-induced apoptosis. J Cell Biol 143:1361–1373
Huot J, Roy G, Lambert H, Chretien P, Landry J (1991) Increased survival after treatments with anticancer agents of Chinese hamster cells expressing the human Mr 27,000 heat shock protein. Cancer Res 51:5245–5252
Ito H, Kamei K, Iwamoto I, Inaguma Y, Kato K (2001) Regulation of the levels of small heat-shock proteins during differentiation of C2C12 cells. Exp Cell Res 266:213–221
Jakob U, Gaestel M, Engels K, Buchner J (1993) Small heat shock proteins are molecular chaperones. J Biol Chem 268:1517–1520
Jantschitsch C, Kindas-Mugge I, Metze D, Amann G, Micksche M, Trautinger F (1998) Expression of the small heat shock protein HSP 27 in developing human skin. Br J Dermatol 139:247–253
Kamradt MC, Chen F, Sam S, Cryns VL (2002) The small heat shock protein alpha B-crystallin negatively regulates apoptosis during myogenic differentiation by inhibiting caspase-3 activation. J Biol Chem 277:38731–38736
Kato K, Hasegawa K, Goto S, Inaguma Y (1994) Dissociation as a result of phosphorylation of an aggregated form of the small stress protein, Hsp27. J Biol Chem 269:11274–11278
Katsogiannou M, Andrieu C, Rocchi P (2014) Heat shock protein 27 phosphorylation state is associated with cancer progression. Front Genet 5:346
Kindas-Mugge I, Trautinger F (1994) Increased expression of the M(r) 27,000 heat shock protein (Hsp27) in in vitro differentiated normal human keratinocytes. Cell Growth Differ 5:777–781
Kostenko S, Moens U (2009) Heat shock protein 27 phosphorylation: kinases, phosphatases, functions and pathology. Cell Mol Life Sci 66:3289–3307
Lambert H, Charette SJ, Bernier AF, Guimond A, Landry J (1999) Hsp27 multimerization mediated by phosphorylation-sensitive intermolecular interactions at the amino terminus. J Biol Chem 274:9378–9385
Landry J, Chretien P, Lambert H, Hickey E, Weber LA (1989) Heat shock resistance confered by expression of the human HSP 27 gene in rodent cells. J Cell Biol 109:7–15
Lee GJ, Roseman AM, Saibil HR, Vierling E (1997) A small heat shock protein stably binds heat-denatured model substrates and can maintain a substrate in a folding-competent state. EMBO J 16:659–671
Lemieux P, Oesterreich S, Lawrence JA, Steeg PS, Hilsenbeck SG, Harvey JM, Fuqua SA (1997) The small heat shock protein Hsp27 increases invasiveness but decreases motility of breast cancer cells. Invasion Metastasis 17:113–123
Loones MT, Chang Y, Morange M (2000) The distribution of heat shock proteins in the nervous system of the unstressed mouse embryo suggests a role in neuronal and non-neuronal differentiation. Cell Stress Chaperones 5:291–305
McClellan AJ, Xia Y, Deutschbauer AM, Davis RW, Gerstein M, Frydman J (2007) Diverse cellular functions of the Hsp90 molecular chaperone uncovered using systems approaches. Cell 131:121–135
Mehlen P, Arrigo A-P (1994) The serum-induced phosphorylation of mammalian Hsp27 correlates with changes in its intracellular localization and levels of oligomerization. Eur J Biochem 221:327–334
Mehlen P, Coronas V, Ljubic-Thibal V, Ducasse C, Granger L, Jourdan F, Arrigo A-P (1999) Small stress protein Hsp27 accumulation during dopamine-mediated differentiation of rat olfactory neurons counteracts apoptosis. Cell Death Differ 6:227–233
Mehlen P, Hickey E, Weber L, Arrigo A-P (1997a) Large unphosphorylated aggregates as the active form of Hsp27 which controls intracellular reactive oxygen species and glutathione levels and generates a protection against TNFa in NIH-3T3-ras cells. Biochem Biophys Res Comm 241:187–192
Mehlen P, Kretzremy C, Briolay J, Fostan P, Mirault ME, Arrigo AP (1995a) Intracellular reactive oxygen species as apparent modulators of heat-shock protein 27 (Hsp27) structural organization and phosphorylation in basal and tumour necrosis factor alpha-treated T47D human carcinoma cells. Biochem J 312:367–375
Mehlen P, Mehlen A, Godet J, Arrigo A-P (1997b) Hsp27 as a switch between differentiation and apoptosis in murine embryonic stem cells. J Biol Chem 272:31657–31665
Mehlen P, Mehlen A, Guillet D, Préville X, Arrigo A-P (1995b) Tumor necrosis factor-a induces changes in the phosphorylation, cellular localization, and oligomerization of human Hsp27, a stress protein that confers cellular resistance to this cytokine. J Cell Biochem 58:248–259
Mehlen P, Préville X, Chareyron P, Briolay J, Klemenz R, Arrigo A-P (1995c) Constitutive expression of human Hsp27, Drosophila Hsp27, or human alpha B-crystallin confers resistance to TNF- and oxidative stress-induced cytotoxicity in stably transfected murine L929 fibroblasts. J Immunol 154:363–374
Mehlen P, Préville X, Kretz-Remy C, Arrigo A-P (1996a) Human Hsp27, Drosophila Hsp27 and human aB-crystallin expression-mediated increase in glutathione is essential for the protective activity of these protein against TNFa-induced cell death. EMBO J 15:2695–2706
Mehlen P, Schulze-Osthoff K, Arrigo A-P (1996b) Small stress proteins as novel regulators of apoptosis. Heat shock protein 27 blocks Fas/APO-1- and staurosporine-induced cell death. J Biol Chem 271:16510–16514
Merendino AM, Paul C, Vignola AM, Costa MA, Melis M, Chiappara G, Izzo V, Bousquet J, Arrigo A-P (2002) Heat shock protein-27 protects human bronchial epithelial cells against oxidative stress-mediated apoptosis: possible implication in asthma. Cell Stress Chaperones 7:269–280
Mounier N, Arrigo A-P (2002) Actin cytoskeleton and small heat shock proteins: how do they interact? Cell Stress Chaperones 7:167–176
Mymrikov EV, Bukach OV, Seit-Nebi AS, Gusev NB (2010) The pivotal role of the beta 7 strand in the intersubunit contacts of different human small heat shock proteins. Cell Stress Chaperones 15:365–377
Mymrikov EV, Seit-Nebi AS, Gusev NB (2011) Large potentials of small heat shock proteins. Physiol Rev 91:1123–1159
Mymrikov EV, Seit-Nebi AS, Gusev NB (2012) Heterooligomeric complexes of human small heat shock proteins. Cell Stress Chaperones 17:157–169
Nagaraja GN, Kaur P, Asea A (2012) Role of human and mouse HspB1 in metastasis. Curr Mol Med 12(9):1142–1150
Nakashima M, Adachi S, Yasuda I, Yamauchi T, Kawaguchi J, Itani M, Yoshioka T, Matsushima-Nishiwaki R, Hirose Y, Kozawa O, Moriwaki H (2011) Phosphorylation status of heat shock protein 27 plays a key role in gemcitabine-induced apoptosis of pancreatic cancer cells. Cancer Lett 313:218–225
Neckers L (2002) Hsp90 inhibitors as novel cancer chemotherapeutic agents. Trends Mol Med 8:S55–S61
O’Callaghan-Sunol C, Gabai VL, Sherman MY (2007) Hsp27 modulates p53 signaling and suppresses cellular senescence. Cancer Res 67:11779–11788
Outeiro TF, Klucken J, Strathearn KE, Liu F, Nguyen P, Rochet JC, Hyman BT, McLean PJ (2006) Small heat shock proteins protect against alpha-synuclein-induced toxicity and aggregation. Biochem Biophys Res Commun 351:631–638
Pandey P, Farber R, Nakazawa A, Kumar S, Bharti A, Nalin C, Weichselbaum R, Kufe D, Kharbanda S (2000) Hsp27 functions as a negative regulator of cytochrome c-dependent activation of procaspase-3. Oncogene 19:1975–1981
Paul C, Manero F, Gonin S, Kretz-Remy C, Virot S, Arrigo A-P (2002) Hsp27 as a negative regulator of cytochrome C release. Mol Cell Biol 22:816–834
Paul C, Simon S, Gibert B, Virot S, Manero F, Arrigo AP (2010) Dynamic processes that reflect anti-apoptotic strategies set up by HspB1 (Hsp27). Exp Cell Res 316:1535–1552
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 15:903–911
Pichon S, Bryckaert M, Berrou E (2004) Control of actin dynamics by p38 MAP kinase—Hsp27 distribution in the lamellipodium of smooth muscle cells. J Cell Sci 117:2569–2577
Preville X, Gaestel M, Arrigo AP (1998a) Phosphorylation is not essential for protection of L929 cells by Hsp25 against H2O2-mediated disruption actin cytoskeleton, a protection which appears related to the redox change mediated by Hsp25. Cell Stress Chaperones 3:177–187
Preville X, Salvemini F, Giraud S, Chaufour S, Paul C, Stepien G, Ursini MV, Arrigo AP (1999) Mammalian small stress proteins protect against oxidative stress through their ability to increase glucose-6-phosphate dehydrogenase activity and by maintaining optimal cellular detoxifying machinery. Exp Cell Res 247:61–78
Preville X, Schultz H, Knauf U, Gaestel M, Arrigo AP (1998b) Analysis of the role of Hsp25 phosphorylation reveals the importance of the oligomerization state of this small heat shock protein in its protective function against TNFalpha- and hydrogen peroxide-induced cell death. J Cell Biochem 69:436–452
Rajagopal P, Liu Y, Shi L, Clouser AF, Klevit RE (2015) Structure of the alpha-crystallin domain from the redox-sensitive chaperone, HSPB1. J Biomol NMR 63:223–228
Rane MJ, Pan Y, Singh S, Powell DW, Wu R, Cummins T, Chen Q, McLeish KR, Klein JB (2003) Heat shock protein 27 controls apoptosis by regulating Akt activation. J Biol Chem 278:27828–27835
Rogalla T, Ehrnsperger M, Preville X, Kotlyarov A, Lutsch G, Ducasse C, Paul C, Wieske M, Arrigo AP, Buchner J, Gaestel M (1999) Regulation of Hsp27 oligomerization, chaperone function, and protective activity against oxidative stress/tumor necrosis factor alpha by phosphorylation. J Biol Chem 274:18947–18956
Samali A, Cotter TG (1996) Heat shock proteins increase resistance to apoptosis. Exp Cell Res 223:163–170
Samali A, Robertson JD, Peterson E, Manero F, van Zeijl L, Paul C, Cotgreave IA, Arrigo AP, Orrenius S (2001) Hsp27 protects mitochondria of thermotolerant cells against apoptotic stimuli. Cell Stress Chaperones 6:49–58
Schultz CR, Golembieski WA, King DA, Brown SL, Brodie C, Rempel SA (2012) Inhibition of HSP27 alone or in combination with pAKT inhibition as therapeutic approaches to target SPARC-induced glioma cell survival. Mol Cancer 11:20
Shakoori AR, Oberdorf AM, Owen TA, Weber LA, Hickey E, Stein JL, Lian JB, Stein GS (1992) Expression of heat shock genes during differentiation of mammalian osteoblasts and promyelocytic leukemia cells. J Cell Biochem 48:277–287
Simon S, Dimitrova V, Gibert B, Virot S, Mounier N, Nivon M, Kretz-Remy C, Corset V, Mehlen P, Arrigo A-P (2013) Analysis of the dominant effects mediated by wild type or R120G mutant of alphaB-crystallin (HspB5) towards Hsp27 (HspB1). PLoS One 8:e70545
Spector NL, Hardy L, Ryan C, Miller WH Jr, Humes JL, Nadler LM, Luedke E (1995) 28-kDa mammalian heat shock protein, a novel substrate of a growth regulatory protease involved in differentiation of human leukemia cells. J Biol Chem 270:1003–1006
Spector NL, Mehlen P, Ryan C, Hardy L, Samson W, Levine H, Nadler LM, Fabre N, Arrigo A-P (1994) Regulation of the 28 kDa heat shock protein by retinoic acid during diferentiation of human leukemic HL-60 cells. FEBS Lett 337:184–188
Spector NL, Ryan C, Samson W, Levine H, Nadler LM, Arrigo A-P (1993) Heat shock protein is a unique marker of growth arrest during macrophage differenciation of HL-60 cells. J Cell Physiol 156:619–625
Spector NL, Samson W, Ryan C, Gribben J, Urba W, Welch WJ, Nadler LM (1992) Growth arrest of human B lymphocytes is accompanied by induction of the low molecular weight mammalian heat shock protein. J Immunol 148:1668–1673
Stahl J, Wobus AM, Ihrig S, Lutsch G, Bielka H (1992) The small heat shock protein Hsp25 is accumulated in P19 embryonal carcinoma cells and embryonic stem cells of line BLC6 during differentiation. Differentiation 51:33–37
Stengel F, Baldwin AJ, Painter AJ, Jaya N, Basha E, Kay LE, Vierling E, Robinson CV, Benesch JL (2010) Quaternary dynamics and plasticity underlie small heat shock protein chaperone function. Proc Natl Acad Sci U S A 107:2007–2012
Sun X, Ou Z, Xie M, Kang R, Fan Y, Niu X, Wang H, Cao L, Tang D (2015) HSPB1 as a novel regulator of ferroptotic cancer cell death. Oncogene 34:5617–5625
Taipale M, Jarosz DF, Lindquist S (2010) HSP90 at the hub of protein homeostasis: emerging mechanistic insights. Nat Rev Mol Cell Biol 11:515–528
Tsvetkova NM, Horvath I, Torok Z, Wolkers WF, Balogi Z, Shigapova N, Crowe LM, Tablin F, Vierling E, Crowe JH, Vigh L (2002) Small heat-shock proteins regulate membrane lipid polymorphism. Proc Natl Acad Sci U S A 99:13504–13509
Vertii A, Hakim C, Kotlyarov A, Gaestel M (2006) Analysis of properties of small heat shock protein Hsp25 in MAPK-activated protein kinase 2 (MK2)-deficient cells: MK2-dependent insolubilization of Hsp25 oligomers correlates with susceptibility to stress. J Biol Chem 281:26966–26975
Wei L, Liu TT, Wang HH, Hong HM, Yu AL, Feng HP, Chang WW (2011) Hsp27 participates in the maintenance of breast cancer stem cells through regulation of epithelial-mesenchymal transition and nuclear factor-kappaB. Breast Cancer Res 13:R101
Welch WJ (1985) Phorbol ester, calcium ionophore, or serum added to quiescent rat embryo fibroblasts cells all result in the elevated phosphorylation of two 28,000-Dalton mammalian stress proteins. J Biol Chem 260:3058–3062
Wettstein G, Bellaye PS, Kolb M, Hammann A, Crestani B, Soler P, Marchal-Somme J, Hazoume A, Gauldie J, Gunther A, Micheau O, Gleave M, Camus P, Garrido C, Bonniaud P (2013) Inhibition of HSP27 blocks fibrosis development and EMT features by promoting Snail degradation. Faseb J: 1549–1560
Wettstein G, Bellaye PS, Micheau O, Bonniaud P (2012) Small heat shock proteins and the cytoskeleton: an essential interplay for cell integrity? Int J Biochem Cell Biol 44:1680–1686
Wu R, Kausar H, Johnson P, Montoya-Durango DE, Merchant M, Rane MJ (2007) Hsp27 regulates Akt activation and polymorphonuclear leukocyte apoptosis by scaffolding MK2 to Akt signal complex. J Biol Chem 282:21598–21608
Wyttenbach A, Sauvageot O, Carmichael J, Diaz-Latoud C, Arrigo AP, Rubinsztein DC (2002) Heat shock protein 27 prevents cellular polyglutamine toxicity and suppresses the increase of reactive oxygen species caused by huntingtin. Hum Mol Genet 11:1137–1151
Yan LJ, Christians ES, Liu L, Xiao X, Sohal RS, Benjamin IJ (2002) Mouse heat shock transcription factor 1 deficiency alters cardiac redox homeostasis and increases mitochondrial oxidative damage. EMBO J 21:5164–5172
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I thank Patrick Mehlen for his support.
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Arrigo, AP. Mammalian HspB1 (Hsp27) is a molecular sensor linked to the physiology and environment of the cell. Cell Stress and Chaperones 22, 517–529 (2017). https://doi.org/10.1007/s12192-017-0765-1
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DOI: https://doi.org/10.1007/s12192-017-0765-1