Cellular and Molecular Life Sciences

, Volume 75, Issue 16, pp 2897–2916 | Cite as

Roles of heat shock factor 1 beyond the heat shock response

  • János Barna
  • Péter Csermely
  • Tibor Vellai


Various stress factors leading to protein damage induce the activation of an evolutionarily conserved cell protective mechanism, the heat shock response (HSR), to maintain protein homeostasis in virtually all eukaryotic cells. Heat shock factor 1 (HSF1) plays a central role in the HSR. HSF1 was initially known as a transcription factor that upregulates genes encoding heat shock proteins (HSPs), also called molecular chaperones, which assist in refolding or degrading injured intracellular proteins. However, recent accumulating evidence indicates multiple additional functions for HSF1 beyond the activation of HSPs. Here, we present a nearly comprehensive list of non-HSP-related target genes of HSF1 identified so far. Through controlling these targets, HSF1 acts in diverse stress-induced cellular processes and molecular mechanisms, including the endoplasmic reticulum unfolded protein response and ubiquitin–proteasome system, multidrug resistance, autophagy, apoptosis, immune response, cell growth arrest, differentiation underlying developmental diapause, chromatin remodelling, cancer development, and ageing. Hence, HSF1 emerges as a major orchestrator of cellular stress response pathways.


Ageing Apoptosis Autophagy Cancer Cell cycle Circadian rhythm Development Differentiation Heat shock factor 1 Heat shock proteins Heat shock response Immune response Multidrug resistance Oxidative stress Proteasome Unfolded protein response 



This work was supported by the grants OTKA (Hungarian Scientific Research Fund) NK78012 and K115378, MEDinPROT Protein Science Research Synergy Program (provided by the Hungarian Academy of Sciences; HAS), and VEKOP (VEKOP-2.3.2-16-2017-00014). B.J and T.V. are also supported by the MTA-ELTE Genetics Research Group (01062).

Author contributions

Each author (JB, PC, and TV) has participated in collecting non-HSP targets of HSF1, characterising the role of HSF1 in functions other than the HSR, and writing the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare no competing interest.

Supplementary material

18_2018_2836_MOESM1_ESM.docx (55 kb)
Supplementary material 1 (DOCX 55 kb)


  1. 1.
    Gomez-Pastor R, Burchfiel ET, Thiele DJ (2018) Regulation of heat shock transcription factors and their roles in physiology and disease. Nat Rev Mol Cell Biol 19(1):4–19. PubMedCrossRefGoogle Scholar
  2. 2.
    Bellaye PS, Burgy O, Causse S, Garrido C, Bonniaud P (2014) Heat shock proteins in fibrosis and wound healing: good or evil? Pharmacol Ther 143(2):119–132. PubMedCrossRefGoogle Scholar
  3. 3.
    Hooper PL, Balogh G, Rivas E, Kavanagh K, Vigh L (2014) The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes. Cell Stress Chaperon 19(4):447–464. CrossRefGoogle Scholar
  4. 4.
    Willis MS, Patterson C (2010) Hold me tight: role of the heat shock protein family of chaperones in cardiac disease. Circulation 122(17):1740–1751. PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Xu Q (2002) Role of heat shock proteins in atherosclerosis. Arterioscler Thromb Vasc Biol 22(10):1547–1559PubMedCrossRefGoogle Scholar
  6. 6.
    Dai C, Sampson SB (2016) HSF1: guardian of proteostasis in cancer. Trends Cell Biol 6(1):17–28. CrossRefGoogle Scholar
  7. 7.
    Dai C, Whitesell L, Rogers AB, Lindquist S (2007) Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis. Cell 130(6):1005–1018. PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Akerfelt M, Morimoto RI, Sistonen L (2010) Heat shock factors: integrators of cell stress, development and lifespan. Nat Rev Mol Cell Biol 11(8):545–555. PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Wu C (1995) Heat shock transcription factors: structure and regulation. Annu Rev Cell Dev Biol 11:441–469. PubMedCrossRefGoogle Scholar
  10. 10.
    Acunzo J, Katsogiannou M, Rocchi P (2012) Small heat shock proteins HSP27 (HspB1), alphaB-crystallin (HspB5) and HSP22 (HspB8) as regulators of cell death. Int J Biochem Cell Biol 44(10):1622–1631. PubMedCrossRefGoogle Scholar
  11. 11.
    Amin J, Ananthan J, Voellmy R (1988) Key features of heat shock regulatory elements. Mol Cell Biol 8(9):3761–3769PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Jaeger AM, Makley LN, Gestwicki JE, Thiele DJ (2014) Genomic heat shock element sequences drive cooperative human heat shock factor 1 DNA binding and selectivity. J Biol Chem 289(44):30459–30469. PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Guertin MJ, Lis JT (2010) Chromatin landscape dictates HSF binding to target DNA elements. PLoS Genet 6(9):e1001114. PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Vihervaara A, Mahat DB, Guertin MJ, Chu T, Danko CG, Lis JT, Sistonen L (2017) Transcriptional response to stress is pre-wired by promoter and enhancer architecture. Nat Commun 8(1):255. PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Pernet L, Faure V, Gilquin B, Dufour-Guerin S, Khochbin S, Vourc’h C (2014) HDAC6-ubiquitin interaction controls the duration of HSF1 activation after heat shock. Mol Biol Cell 25(25):4187–4194. PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Voellmy R (2004) On mechanisms that control heat shock transcription factor activity in metazoan cells. Cell Stress Chaperon 9(2):122–133CrossRefGoogle Scholar
  17. 17.
    Westerheide SD, Anckar J, Stevens SM Jr, Sistonen L, Morimoto RI (2009) Stress-inducible regulation of heat shock factor 1 by the deacetylase SIRT1. Science 323(5917):1063–1066. PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Hietakangas V, Anckar J, Blomster HA, Fujimoto M, Palvimo JJ, Nakai A, Sistonen L (2006) PDSM, a motif for phosphorylation-dependent SUMO modification. Proc Natl Acad Sci USA 103(1):45–50. PubMedCrossRefGoogle Scholar
  19. 19.
    Barna J, Princz A, Kosztelnik M, Hargitai B, Takacs-Vellai K, Vellai T (2012) Heat shock factor-1 intertwines insulin/IGF-1, TGF-beta and cGMP signaling to control development and aging. BMC Dev Biol 12:32. PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Chiang WC, Ching TT, Lee HC, Mousigian C, Hsu AL (2012) HSF-1 regulators DDL-1/2 link insulin-like signaling to heat-shock responses and modulation of longevity. Cell 148(1–2):322–334. PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Calderwood SK, Xie Y, Wang X, Khaleque MA, Chou SD, Murshid A, Prince T, Zhang Y (2010) Signal transduction pathways leading to heat shock transcription. Sign Transduct Insights 2:13–24. PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Choi HS, Li B, Lin Z, Huang E, Liu AY (1991) cAMP and cAMP-dependent protein kinase regulate the human heat shock protein 70 gene promoter activity. J Biol Chem 266(18):11858–11865PubMedGoogle Scholar
  23. 23.
    Lindquist S, Craig EA (1988) The heat-shock proteins. Annu Rev Genet 22:631–677. PubMedCrossRefGoogle Scholar
  24. 24.
    Richter K, Haslbeck M, Buchner J (2010) The heat shock response: life on the verge of death. Mol Cell 40(2):253–266. PubMedCrossRefGoogle Scholar
  25. 25.
    Buchner J (1999) Hsp90 and Co.—a holding for folding. Trends Biochem Sci 24(4):136–141PubMedCrossRefGoogle Scholar
  26. 26.
    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(2):129–168PubMedCrossRefGoogle Scholar
  27. 27.
    Pratt WB, Toft DO (1997) Steroid receptor interactions with heat shock protein and immunophilin chaperones. Endocr Rev 18(3):306–360. PubMedCrossRefGoogle Scholar
  28. 28.
    Jedlicka P, Mortin MA, Wu C (1997) Multiple functions of Drosophila heat shock transcription factor in vivo. EMBO J 16(9):2452–2462. PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Morton EA, Lamitina T (2013) Caenorhabditis elegans HSF-1 is an essential nuclear protein that forms stress granule-like structures following heat shock. Aging Cell 12(1):112–120. PubMedCrossRefGoogle Scholar
  30. 30.
    Sorger PK, Pelham HR (1988) Yeast heat shock factor is an essential DNA-binding protein that exhibits temperature-dependent phosphorylation. Cell 54(6):855–864PubMedCrossRefGoogle Scholar
  31. 31.
    Solis EJ, Pandey JP, Zheng X, Jin DX, Gupta PB, Airoldi EM, Pincus D, Denic V (2016) Defining the essential function of yeast Hsf1 reveals a compact transcriptional program for maintaining eukaryotic proteostasis. Mol Cell 63(1):60–71. PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Xiao X, Zuo X, Davis AA, McMillan DR, Curry BB, Richardson JA, Benjamin IJ (1999) HSF1 is required for extra-embryonic development, postnatal growth and protection during inflammatory responses in mice. EMBO J 18(21):5943–5952. PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Stephanou A, Latchman DS (2011) Transcriptional modulation of heat-shock protein gene expression. Biochem Res Int 2011:238601. PubMedCrossRefGoogle Scholar
  34. 34.
    Birch-Machin I, Gao S, Huen D, McGirr R, White RA, Russell S (2005) Genomic analysis of heat-shock factor targets in Drosophila. Genome Biol 6(7):R63. PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Brunquell J, Morris S, Lu Y, Cheng F, Westerheide SD (2016) The genome-wide role of HSF-1 in the regulation of gene expression in Caenorhabditis elegans. BMC Genom 17:559. CrossRefGoogle Scholar
  36. 36.
    Li J, Chauve L, Phelps G, Brielmann RM, Morimoto RI (2016) E2F coregulates an essential HSF developmental program that is distinct from the heat-shock response. Genes Dev 30(18):2062–2075. PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Mahat DB, Salamanca HH, Duarte FM, Danko CG, Lis JT (2016) Mammalian heat shock response and mechanisms underlying its genome-wide transcriptional regulation. Mol Cell 62(1):63–78. PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Hahn JS, Hu Z, Thiele DJ, Iyer VR (2004) Genome-wide analysis of the biology of stress responses through heat shock transcription factor. Mol Cell Biol 24(12):5249–5256. PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Trinklein ND, Murray JI, Hartman SJ, Botstein D, Myers RM (2004) The role of heat shock transcription factor 1 in the genome-wide regulation of the mammalian heat shock response. Mol Biol Cell 15(3):1254–1261. PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Ahn SG, Thiele DJ (2003) Redox regulation of mammalian heat shock factor 1 is essential for Hsp gene activation and protection from stress. Genes Dev 17(4):516–528. PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Hetz C (2012) The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol 13(2):89–102. PubMedCrossRefGoogle Scholar
  42. 42.
    Weindling E, Bar-Nun S (2015) Sir2 links the unfolded protein response and the heat shock response in a stress response network. Biochem Biophys Res Commun 457(3):473–478. PubMedCrossRefGoogle Scholar
  43. 43.
    Liu Y, Chang A (2008) Heat shock response relieves ER stress. EMBO J 27(7):1049–1059. PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Hou J, Tang H, Liu Z, Osterlund T, Nielsen J, Petranovic D (2014) Management of the endoplasmic reticulum stress by activation of the heat shock response in yeast. FEMS Yeast Res 14(3):481–494. PubMedCrossRefGoogle Scholar
  45. 45.
    Marcu MG, Doyle M, Bertolotti A, Ron D, Hendershot L, Neckers L (2002) Heat shock protein 90 modulates the unfolded protein response by stabilizing IRE1alpha. Mol Cell Biol 22(24):8506–8513PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Gupta S, Deepti A, Deegan S, Lisbona F, Hetz C, Samali A (2010) HSP72 protects cells from ER stress-induced apoptosis via enhancement of IRE1alpha-XBP1 signaling through a physical interaction. PLoS Biol 8(7):e1000410. PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Heldens L, Hensen SM, Onnekink C, van Genesen ST, Dirks RP, Lubsen NH (2011) An atypical unfolded protein response in heat shocked cells. PLoS One 6(8):e23512. PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Zito E (2015) ERO1: a protein disulfide oxidase and H2O2 producer. Free Radic Biol Med 83:299–304. PubMedCrossRefGoogle Scholar
  49. 49.
    Takemori Y, Sakaguchi A, Matsuda S, Mizukami Y, Sakurai H (2006) Stress-induced transcription of the endoplasmic reticulum oxidoreductin gene ERO1 in the yeast Saccharomyces cerevisiae. Mol Genet Genom 275(1):89–96. CrossRefGoogle Scholar
  50. 50.
    Cox JS, Walter P (1996) A novel mechanism for regulating activity of a transcription factor that controls the unfolded protein response. Cell 87(3):391–404PubMedCrossRefGoogle Scholar
  51. 51.
    Chuang YY, Chen Y, Gadisetti Chandramouli VR, Cook JA, Coffin D, Tsai MH, DeGraff W, Yan H, Zhao S, Russo A, Liu ET, Mitchell JB (2002) Gene expression after treatment with hydrogen peroxide, menadione, or t-butyl hydroperoxide in breast cancer cells. Cancer Res 62(21):6246–6254PubMedGoogle Scholar
  52. 52.
    Lee J, Bruce-Keller AJ, Kruman Y, Chan SL, Mattson MP (1999) 2-Deoxy-d-glucose protects hippocampal neurons against excitotoxic and oxidative injury: evidence for the involvement of stress proteins. J Neurosci Res 57(1):48–61.<48:AID-JNR6>3.0.CO;2-LPubMedCrossRefGoogle Scholar
  53. 53.
    Yamamoto A, Ueda J, Yamamoto N, Hashikawa N, Sakurai H (2007) Role of heat shock transcription factor in Saccharomyces cerevisiae oxidative stress response. Eukaryot Cell 6(8):1373–1379. PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Kim IS, Kim H, Kim YS, Jin I, Yoon HS (2013) HSF1-mediated oxidative stress response to menadione in Saccharomyces cerevisiae KNU5377Y3 by using proteomic approach. Adv Biosci Biotechnol 4:44–54CrossRefGoogle Scholar
  55. 55.
    Motohashi H, Yamamoto M (2004) Nrf2-Keap1 defines a physiologically important stress response mechanism. Trends Mol Med 10(11):549–557. PubMedCrossRefGoogle Scholar
  56. 56.
    Jain A, Lamark T, Sjottem E, Larsen KB, Awuh JA, Overvatn A, McMahon M, Hayes JD, Johansen T (2010) p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription. J Biol Chem 285(29):22576–22591. PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Samarasinghe B, Wales CT, Taylor FR, Jacobs AT (2014) Heat shock factor 1 confers resistance to Hsp90 inhibitors through p62/SQSTM1 expression and promotion of autophagic flux. Biochem Pharmacol 87(3):445–455. PubMedCrossRefGoogle Scholar
  58. 58.
    Watanabe Y, Tsujimura A, Taguchi K, Tanaka M (2017) HSF1 stress response pathway regulates autophagy receptor SQSTM1/p62-associated proteostasis. Autophagy 13(1):133–148. PubMedCrossRefGoogle Scholar
  59. 59.
    Kim KH, Jeong JY, Surh YJ, Kim KW (2010) Expression of stress-response ATF3 is mediated by Nrf2 in astrocytes. Nucleic Acids Res 38(1):48–59. PubMedCrossRefGoogle Scholar
  60. 60.
    Takii R, Inouye S, Fujimoto M, Nakamura T, Shinkawa T, Prakasam R, Tan K, Hayashida N, Ichikawa H, Hai T, Nakai A (2010) Heat shock transcription factor 1 inhibits expression of IL-6 through activating transcription factor 3. J Immunol 184(2):1041–1048. PubMedCrossRefGoogle Scholar
  61. 61.
    Mehlen P, Kretz-Remy C, Preville X, Arrigo AP (1996) Human hsp27, Drosophila hsp27 and human alphaB-crystallin expression-mediated increase in glutathione is essential for the protective activity of these proteins against TNFalpha-induced cell death. EMBO J 15(11):2695–2706PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    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(19):5164–5172PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Vellai T (2009) Autophagy genes and ageing. Cell Death Differ 16(1):94–102. PubMedCrossRefGoogle Scholar
  64. 64.
    Vellai T, Takacs-Vellai K, Sass M, Klionsky DJ (2009) The regulation of aging: does autophagy underlie longevity? Trends Cell Biol 19(10):487–494. PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Dokladny K, Zuhl MN, Mandell M, Bhattacharya D, Schneider S, Deretic V, Moseley PL (2013) Regulatory coordination between two major intracellular homeostatic systems: heat shock response and autophagy. J Biol Chem 288(21):14959–14972. PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Nivon M, Richet E, Codogno P, Arrigo AP, Kretz-Remy C (2009) Autophagy activation by NFkappaB is essential for cell survival after heat shock. Autophagy 5(6):766–783PubMedCrossRefGoogle Scholar
  67. 67.
    Zhao Y, Gong S, Shunmei E, Zou J (2009) Induction of macroautophagy by heat. Mol Biol Rep 36(8):2323–2327. PubMedCrossRefGoogle Scholar
  68. 68.
    Desai S, Liu Z, Yao J, Patel N, Chen J, Wu Y, Ahn EE, Fodstad O, Tan M (2013) Heat shock factor 1 (HSF1) controls chemoresistance and autophagy through transcriptional regulation of autophagy-related protein 7 (ATG7). J Biol Chem 288(13):9165–9176. PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Mishra SK, Tripp J, Winkelhaus S, Tschiersch B, Theres K, Nover L, Scharf KD (2002) In the complex family of heat stress transcription factors, HsfA1 has a unique role as master regulator of thermotolerance in tomato. Genes Dev 16(12):1555–1567. PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Ohama N, Sato H, Shinozaki K, Yamaguchi-Shinozaki K (2017) Transcriptional regulatory network of plant heat stress response. Trends Plant Sci 22(1):53–65. PubMedCrossRefGoogle Scholar
  71. 71.
    Wang Y, Cai S, Yin L, Shi K, Xia X, Zhou Y, Yu J, Zhou J (2015) Tomato HsfA1a plays a critical role in plant drought tolerance by activating ATG genes and inducing autophagy. Autophagy 11(11):2033–2047. PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Kumsta C, Chang JT, Schmalz J, Hansen M (2017) Hormetic heat stress and HSF-1 induce autophagy to improve survival and proteostasis in C. elegans. Nat Commun 8:14337. PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Sigmond T, Barna J, Toth ML, Takacs-Vellai K, Pasti G, Kovacs AL, Vellai T (2008) Autophagy in Caenorhabditis elegans. Methods Enzymol 451:521–540. PubMedCrossRefGoogle Scholar
  74. 74.
    Fodor E, Sigmond T, Ari E, Lengyel K, Takacs-Vellai K, Varga M, Vellai T (2017) Methods to study autophagy in Zebrafish. Methods Enzymol 588:467–496. PubMedCrossRefGoogle Scholar
  75. 75.
    Varga M, Fodor E, Vellai T (2015) Autophagy in zebrafish. Methods 75:172–180. PubMedCrossRefGoogle Scholar
  76. 76.
    Kawazoe Y, Nakai A, Tanabe M, Nagata K (1998) Proteasome inhibition leads to the activation of all members of the heat-shock-factor family. Eur J Biochem 255(2):356–362PubMedCrossRefGoogle Scholar
  77. 77.
    Lecomte S, Desmots F, Le Masson F, Le Goff P, Michel D, Christians ES, Le Drean Y (2010) Roles of heat shock factor 1 and 2 in response to proteasome inhibition: consequence on p53 stability. Oncogene 29(29):4216–4224. PubMedCrossRefGoogle Scholar
  78. 78.
    Mathew A, Mathur SK, Morimoto RI (1998) Heat shock response and protein degradation: regulation of HSF2 by the ubiquitin-proteasome pathway. Mol Cell Biol 18(9):5091–5098PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Pirkkala L, Alastalo TP, Zuo X, Benjamin IJ, Sistonen L (2000) Disruption of heat shock factor 1 reveals an essential role in the ubiquitin proteolytic pathway. Mol Cell Biol 20(8):2670–2675PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Vihervaara A, Sergelius C, Vasara J, Blom MA, Elsing AN, Roos-Mattjus P, Sistonen L (2013) Transcriptional response to stress in the dynamic chromatin environment of cycling and mitotic cells. Proc Natl Acad Sci USA 110(36):E3388–E3397. PubMedCrossRefGoogle Scholar
  81. 81.
    Song S, Kole S, Precht P, Pazin MJ, Bernier M (2010) Activation of heat shock factor 1 plays a role in pyrrolidine dithiocarbamate-mediated expression of the co-chaperone BAG3. Int J Biochem Cell Biol 42(11):1856–1863. PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Kinet MJ, Malin JA, Abraham MC, Blum ES, Silverman MR, Lu Y, Shaham S (2016) HSF-1 activates the ubiquitin proteasome system to promote non-apoptotic developmental cell death in C. elegans. eLife 5:73. CrossRefGoogle Scholar
  83. 83.
    Beere HM (2005) Death versus survival: functional interaction between the apoptotic and stress-inducible heat shock protein pathways. J Clin Investig 115(10):2633–2639. PubMedCrossRefGoogle Scholar
  84. 84.
    Tchenio T, Havard M, Martinez LA, Dautry F (2006) Heat shock-independent induction of multidrug resistance by heat shock factor 1. Mol Cell Biol 26(2):580–591. PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Vilaboa NE, Galan A, Troyano A, de Blas E, Aller P (2000) Regulation of multidrug resistance 1 (MDR1)/P-glycoprotein gene expression and activity by heat-shock transcription factor 1 (HSF1). J Biol Chem 275(32):24970–24976. PubMedCrossRefGoogle Scholar
  86. 86.
    Vydra N, Toma A, Glowala-Kosinska M, Gogler-Piglowska A, Widlak W (2013) Overexpression of Heat Shock Transcription Factor 1 enhances the resistance of melanoma cells to doxorubicin and paclitaxel. BMC Cancer 13:504. PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Krishnamurthy K, Vedam K, Kanagasabai R, Druhan LJ, Ilangovan G (2012) Heat shock factor-1 knockout induces multidrug resistance gene, MDR1b, and enhances P-glycoprotein (ABCB1)-based drug extrusion in the heart. Proc Natl Acad Sci USA 109(23):9023–9028. PubMedCrossRefGoogle Scholar
  88. 88.
    Inouye S, Fujimoto M, Nakamura T, Takaki E, Hayashida N, Hai T, Nakai A (2007) Heat shock transcription factor 1 opens chromatin structure of interleukin-6 promoter to facilitate binding of an activator or a repressor. J Biol Chem 282(45):33210–33217. PubMedCrossRefGoogle Scholar
  89. 89.
    Cotto J, Fox S, Morimoto R (1997) HSF1 granules: a novel stress-induced nuclear compartment of human cells. J Cell Sci 110(Pt 23):2925–2934PubMedGoogle Scholar
  90. 90.
    Biamonti G, Vourc’h C (2010) Nuclear stress bodies. Cold Spring Harb Perspect Biol 2(6):a000695. PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Alastalo TP, Hellesuo M, Sandqvist A, Hietakangas V, Kallio M, Sistonen L (2003) Formation of nuclear stress granules involves HSF2 and coincides with the nucleolar localization of Hsp70. J Cell Sci 116(Pt 17):3557–3570. PubMedCrossRefGoogle Scholar
  92. 92.
    Denegri M, Moralli D, Rocchi M, Biggiogera M, Raimondi E, Cobianchi F, De Carli L, Riva S, Biamonti G (2002) Human chromosomes 9, 12, and 15 contain the nucleation sites of stress-induced nuclear bodies. Mol Biol Cell 13(6):2069–2079. PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Jolly C, Konecny L, Grady DL, Kutskova YA, Cotto JJ, Morimoto RI, Vourc’h C (2002) In vivo binding of active heat shock transcription factor 1 to human chromosome 9 heterochromatin during stress. J Cell Biol 156(5):775–781. PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Jolly C, Metz A, Govin J, Vigneron M, Turner BM, Khochbin S, Vourc’h C (2004) Stress-induced transcription of satellite III repeats. J Cell Biol 164(1):25–33. PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Rizzi N, Denegri M, Chiodi I, Corioni M, Valgardsdottir R, Cobianchi F, Riva S, Biamonti G (2004) Transcriptional activation of a constitutive heterochromatic domain of the human genome in response to heat shock. Mol Biol Cell 15(2):543–551. PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Denegri M, Chiodi I, Corioni M, Cobianchi F, Riva S, Biamonti G (2001) Stress-induced nuclear bodies are sites of accumulation of pre-mRNA processing factors. Mol Biol Cell 12(11):3502–3514PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Metz A, Soret J, Vourc’h C, Tazi J, Jolly C (2004) A key role for stress-induced satellite III transcripts in the relocalization of splicing factors into nuclear stress granules. J Cell Sci 117(Pt 19):4551–4558. PubMedCrossRefGoogle Scholar
  98. 98.
    Goenka A, Sengupta S, Pandey R, Parihar R, Mohanta GC, Mukerji M, Ganesh S (2016) Human satellite-III non-coding RNAs modulate heat-shock-induced transcriptional repression. J Cell Sci 129(19):3541–3552. PubMedCrossRefGoogle Scholar
  99. 99.
    Romano GH, Harari Y, Yehuda T, Podhorzer A, Rubinstein L, Shamir R, Gottlieb A, Silberberg Y, Pe’er D, Ruppin E, Sharan R, Kupiec M (2013) Environmental stresses disrupt telomere length homeostasis. PLoS Genet 9(9):e1003721. PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Schoeftner S, Blasco MA (2008) Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II. Nat Cell Biol 10(2):228–236. PubMedCrossRefGoogle Scholar
  101. 101.
    Martinez-Guitarte JL, Diez JL, Morcillo G (2008) Transcription and activation under environmental stress of the complex telomeric repeats of Chironomus thummi. Chromosome Res 16(8):1085–1096. PubMedCrossRefGoogle Scholar
  102. 102.
    Azzalin CM, Reichenbach P, Khoriauli L, Giulotto E, Lingner J (2007) Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends. Science 318(5851):798–801. PubMedCrossRefGoogle Scholar
  103. 103.
    Maeda T, Guan JZ, Koyanagi M, Makino N (2013) Alterations in the telomere length distribution and the subtelomeric methylation status in human vascular endothelial cells under elevated temperature in culture condition. Aging Clin Exp Res 25(3):231–238. PubMedCrossRefGoogle Scholar
  104. 104.
    Porro A, Feuerhahn S, Delafontaine J, Riethman H, Rougemont J, Lingner J (2014) Functional characterization of the TERRA transcriptome at damaged telomeres. Nat Commun 5:5379. PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Koskas S, Decottignies A, Dufour S, Pezet M, Verdel A, Vourc’h C, Faure V (2017) Heat shock factor 1 promotes TERRA transcription and telomere protection upon heat stress. Nucleic Acids Res 45(11):6321–6333. PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Corey LL, Weirich CS, Benjamin IJ, Kingston RE (2003) Localized recruitment of a chromatin-remodeling activity by an activator in vivo drives transcriptional elongation. Genes Dev 17(11):1392–1401. PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Thomson S, Hollis A, Hazzalin CA, Mahadevan LC (2004) Distinct stimulus-specific histone modifications at hsp70 chromatin targeted by the transcription factor heat shock factor-1. Mol Cell 15(4):585–594. PubMedCrossRefGoogle Scholar
  108. 108.
    Sullivan EK, Weirich CS, Guyon JR, Sif S, Kingston RE (2001) Transcriptional activation domains of human heat shock factor 1 recruit human SWI/SNF. Mol Cell Biol 21(17):5826–5837PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Shivaswamy S, Iyer VR (2008) Stress-dependent dynamics of global chromatin remodeling in yeast: dual role for SWI/SNF in the heat shock stress response. Mol Cell Biol 28(7):2221–2234. PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Tsukiyama T, Becker PB, Wu C (1994) ATP-dependent nucleosome disruption at a heat-shock promoter mediated by binding of GAGA transcription factor. Nature 367(6463):525–532. PubMedCrossRefGoogle Scholar
  111. 111.
    Morgan WD (1989) Transcription factor Sp1 binds to and activates a human hsp70 gene promoter. Mol Cell Biol 9(9):4099–4104PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Martinez-Balbas MA, Dey A, Rabindran SK, Ozato K, Wu C (1995) Displacement of sequence-specific transcription factors from mitotic chromatin. Cell 83(1):29–38PubMedCrossRefGoogle Scholar
  113. 113.
    Duarte FM, Fuda NJ, Mahat DB, Core LJ, Guertin MJ, Lis JT (2016) Transcription factors GAF and HSF act at distinct regulatory steps to modulate stress-induced gene activation. Genes Dev 30(15):1731–1746. PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Stankiewicz AR, Lachapelle G, Foo CP, Radicioni SM, Mosser DD (2005) Hsp70 inhibits heat-induced apoptosis upstream of mitochondria by preventing Bax translocation. J Biol Chem 280(46):38729–38739. PubMedCrossRefGoogle Scholar
  115. 115.
    Chauhan D, Li G, Hideshima T, Podar K, Mitsiades C, Mitsiades N, Catley L, Tai YT, Hayashi T, Shringarpure R, Burger R, Munshi N, Ohtake Y, Saxena S, Anderson KC (2003) Hsp27 inhibits release of mitochondrial protein Smac in multiple myeloma cells and confers dexamethasone resistance. Blood 102(9):3379–3386. PubMedCrossRefGoogle Scholar
  116. 116.
    Paul C, Manero F, Gonin S, Kretz-Remy C, Virot S, Arrigo AP (2002) Hsp27 as a negative regulator of cytochrome C release. Mol Cell Biol 22(3):816–834PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Rocchi P, Jugpal P, So A, Sinneman S, Ettinger S, Fazli L, Nelson C, Gleave M (2006) Small interference RNA targeting heat-shock protein 27 inhibits the growth of prostatic cell lines and induces apoptosis via caspase-3 activation in vitro. BJU Int 98(5):1082–1089. PubMedCrossRefGoogle Scholar
  118. 118.
    Voss OH, Batra S, Kolattukudy SJ, Gonzalez-Mejia ME, Smith JB, Doseff AI (2007) Binding of caspase-3 prodomain to heat shock protein 27 regulates monocyte apoptosis by inhibiting caspase-3 proteolytic activation. J Biol Chem 282(34):25088–25099. PubMedCrossRefGoogle Scholar
  119. 119.
    Du ZX, Zhang HY, Meng X, Gao YY, Zou RL, Liu BQ, Guan Y, Wang HQ (2009) Proteasome inhibitor MG132 induces BAG3 expression through activation of heat shock factor 1. J Cell Physiol 218(3):631–637. PubMedCrossRefGoogle Scholar
  120. 120.
    Franceschelli S, Rosati A, Lerose R, De Nicola S, Turco MC, Pascale M (2008) Bag3 gene expression is regulated by heat shock factor 1. J Cell Physiol 215(3):575–577. PubMedCrossRefGoogle Scholar
  121. 121.
    Feng Y, Huang W, Meng W, Jegga AG, Wang Y, Cai W, Kim HW, Pasha Z, Wen Z, Rao F, Modi RM, Yu X, Ashraf M (2014) Heat shock improves Sca-1 + stem cell survival and directs ischemic cardiomyocytes toward a prosurvival phenotype via exosomal transfer: a critical role for HSF1/miR-34a/HSP70 pathway. Stem Cells 32(2):462–472. PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Tran SE, Meinander A, Holmstrom TH, Rivero-Muller A, Heiskanen KM, Linnau EK, Courtney MJ, Mosser DD, Sistonen L, Eriksson JE (2003) Heat stress downregulates FLIP and sensitizes cells to Fas receptor-mediated apoptosis. Cell Death Differ 10(10):1137–1147. PubMedCrossRefGoogle Scholar
  123. 123.
    Xia W, Voellmy R, Spector NL (2000) Sensitization of tumor cells to fas killing through overexpression of heat-shock transcription factor 1. J Cell Physiol 183(3):425–431.<425::AID-JCP16>3.0.CO;2-MPubMedCrossRefGoogle Scholar
  124. 124.
    Hayashida N, Inouye S, Fujimoto M, Tanaka Y, Izu H, Takaki E, Ichikawa H, Rho J, Nakai A (2006) A novel HSF1-mediated death pathway that is suppressed by heat shock proteins. EMBO J 25(20):4773–4783. PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Neef R, Kuske MA, Prols E, Johnson JP (2002) Identification of the human PHLDA1/TDAG51 gene: down-regulation in metastatic melanoma contributes to apoptosis resistance and growth deregulation. Cancer Res 62(20):5920–5929PubMedGoogle Scholar
  126. 126.
    Shunmei E, Zhao Y, Huang Y, Lai K, Chen C, Zeng J, Zou J (2010) Heat shock factor 1 is a transcription factor of Fas gene. Mol Cell 29(5):527–531. CrossRefGoogle Scholar
  127. 127.
    Cohen O, Inbal B, Kissil JL, Raveh T, Berissi H, Spivak-Kroizaman T, Feinstein E, Kimchi A (1999) DAP-kinase participates in TNF-alpha- and Fas-induced apoptosis and its function requires the death domain. J Cell Biol 146(1):141–148PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Rennier K, Ji JY (2012) Shear stress regulates expression of death-associated protein kinase in suppressing TNFalpha-induced endothelial apoptosis. J Cell Physiol 227(6):2398–2411. PubMedCrossRefGoogle Scholar
  129. 129.
    Benderska N, Ivanovska J, Rau TT, Schulze-Luehrmann J, Mohan S, Chakilam S, Gandesiri M, Ziesche E, Fischer T, Soder S, Agaimy A, Distel L, Sticht H, Mahadevan V, Schneider-Stock R (2014) DAPK-HSF1 interaction as a positive-feedback mechanism stimulating TNF-induced apoptosis in colorectal cancer cells. J Cell Sci 127(Pt 24):5273–5287. PubMedCrossRefGoogle Scholar
  130. 130.
    Akashi M, Nishida E (2000) Involvement of the MAP kinase cascade in resetting of the mammalian circadian clock. Genes Dev 14(6):645–649PubMedPubMedCentralGoogle Scholar
  131. 131.
    Akerfelt M, Vihervaara A, Laiho A, Conter A, Christians ES, Sistonen L, Henriksson E (2010) Heat shock transcription factor 1 localizes to sex chromatin during meiotic repression. J Biol Chem 285(45):34469–34476. PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Aligue R, Akhavan-Niak H, Russell P (1994) A role for Hsp90 in cell cycle control: Wee1 tyrosine kinase activity requires interaction with Hsp90. EMBO J 13(24):6099–6106PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Munoz MJ, Jimenez J (1999) Genetic interactions between Hsp90 and the Cdc2 mitotic machinery in the fission yeast Schizosaccharomyces pombe. Mol Gen Genet 261(2):242–250PubMedCrossRefGoogle Scholar
  134. 134.
    Nakai A, Ishikawa T (2001) Cell cycle transition under stress conditions controlled by vertebrate heat shock factors. EMBO J 20(11):2885–2895. PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Aladzsity I, Toth ML, Sigmond T, Szabo E, Bicsak B, Barna J, Regos A, Orosz L, Kovacs AL, Vellai T (2007) Autophagy genes unc-51 and bec-1 are required for normal cell size in Caenorhabditis elegans. Genetics 177(1):655–660. PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Ishikawa T, Igarashi T, Hata K, Fujita T (1999) c-fos induction by heat, arsenite, and cadmium is mediated by a heat shock element in its promoter. Biochem Biophys Res Commun 254(3):566–571. PubMedCrossRefGoogle Scholar
  137. 137.
    Ishikawa T, Sekine N, Hata K, Igarashi T, Fujita T (2000) Prostaglandin A1 enhances c-fos expression and activating protein-1 activity. Mol Cell Endocrinol 164(1–2):77–85PubMedCrossRefGoogle Scholar
  138. 138.
    Wilkerson DC, Skaggs HS, Sarge KD (2007) HSF2 binds to the Hsp90, Hsp27, and c-Fos promoters constitutively and modulates their expression. Cell Stress Chaperon 12(3):283–290CrossRefGoogle Scholar
  139. 139.
    Sawai M, Ishikawa Y, Ota A, Sakurai H (2013) The proto-oncogene JUN is a target of the heat shock transcription factor HSF1. FEBS J 280(24):6672–6680. PubMedCrossRefGoogle Scholar
  140. 140.
    Zhao YY, Gao XP, Zhao YD, Mirza MK, Frey RS, Kalinichenko VV, Wang IC, Costa RH, Malik AB (2006) Endothelial cell-restricted disruption of FoxM1 impairs endothelial repair following LPS-induced vascular injury. J Clin Investig 116(9):2333–2343. PubMedCrossRefGoogle Scholar
  141. 141.
    Leung TW, Lin SS, Tsang AC, Tong CS, Ching JC, Leung WY, Gimlich R, Wong GG, Yao KM (2001) Over-expression of FoxM1 stimulates cyclin B1 expression. FEBS Lett 507(1):59–66PubMedCrossRefGoogle Scholar
  142. 142.
    Dai B, Gong A, Jing Z, Aldape KD, Kang SH, Sawaya R, Huang S (2013) Forkhead box M1 is regulated by heat shock factor 1 and promotes glioma cells survival under heat shock stress. J Biol Chem 288(3):1634–1642. PubMedCrossRefGoogle Scholar
  143. 143.
    Yang X, Wang J, Liu S, Yan Q (2014) HSF1 and Sp1 regulate FUT4 gene expression and cell proliferation in breast cancer cells. J Cell Biochem 115(1):168–178. PubMedCrossRefGoogle Scholar
  144. 144.
    Ishikawa Y, Sakurai H (2015) Heat-induced expression of the immediate-early gene IER5 and its involvement in the proliferation of heat-shocked cells. FEBS J 282(2):332–340. PubMedCrossRefGoogle Scholar
  145. 145.
    Gabai VL, Meng L, Kim G, Mills TA, Benjamin IJ, Sherman MY (2012) Heat shock transcription factor Hsf1 is involved in tumor progression via regulation of hypoxia-inducible factor 1 and RNA-binding protein HuR. Mol Cell Biol 32(5):929–940. PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    Chou SD, Murshid A, Eguchi T, Gong J, Calderwood SK (2015) HSF1 regulation of beta-catenin in mammary cancer cells through control of HuR/elavL1 expression. Oncogene 34(17):2178–2188. PubMedCrossRefGoogle Scholar
  147. 147.
    Su KH, Cao J, Tang Z, Dai S, He Y, Sampson SB, Benjamin IJ, Dai C (2016) HSF1 critically attunes proteotoxic stress sensing by mTORC1 to combat stress and promote growth. Nat Cell Biol 18(5):527–539. PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Jolly C, Morimoto RI (2000) Role of the heat shock response and molecular chaperones in oncogenesis and cell death. J Natl Cancer Inst 92(19):1564–1572PubMedCrossRefGoogle Scholar
  149. 149.
    Mendillo ML, Santagata S, Koeva M, Bell GW, Hu R, Tamimi RM, Fraenkel E, Ince TA, Whitesell L, Lindquist S (2012) HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers. Cell 150(3):549–562. PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Schulz R, Streller F, Scheel AH, Ruschoff J, Reinert MC, Dobbelstein M, Marchenko ND, Moll UM (2014) HER2/ErbB2 activates HSF1 and thereby controls HSP90 clients including MIF in HER2-overexpressing breast cancer. Cell Death Dis 5:e980. PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Semenza GL (2003) Targeting HIF-1 for cancer therapy. Nat Rev Cancer 3(10):721–732. PubMedCrossRefGoogle Scholar
  152. 152.
    Almeida DV, Nornberg BF, Geracitano LA, Barros DM, Monserrat JM, Marins LF (2010) Induction of phase II enzymes and hsp70 genes by copper sulfate through the electrophile-responsive element (EpRE): insights obtained from a transgenic zebrafish model carrying an orthologous EpRE sequence of mammalian origin. Fish Physiol Biochem 36(3):347–353. PubMedCrossRefGoogle Scholar
  153. 153.
    Joo HJ, Park S, Kim KY, Kim MY, Kim H, Park D, Paik YK (2016) HSF-1 is involved in regulation of ascaroside pheromone biosynthesis by heat stress in Caenorhabditis elegans. Biochem J 473(6):789–796. PubMedCrossRefGoogle Scholar
  154. 154.
    Takács-Vellai K, Bayci A, Vellai T (2006) Autophagy in neuronal cell loss: a road to death. BioEssays 28(11):1126–1131PubMedCrossRefGoogle Scholar
  155. 155.
    Vellai T, Tóth ML, Kovács AL (2007) Janus-faced autophagy: a dual role of cellular self-eating in neurodegeneration? Autophagy 3(5):461–463PubMedCrossRefGoogle Scholar
  156. 156.
    Vellai T, Takács-Vellai K (2010) Regulation of protein turnover by longevity pathways. Adv Exp Med Biol 694:69–80PubMedCrossRefGoogle Scholar
  157. 157.
    Sturm A, Ivics Z, Vellai T (2015) The mechanism of ageing: primary role of transposable elements in genome disintegration. Cell Mol Life Sci 72(10):1839–1847. PubMedCrossRefGoogle Scholar
  158. 158.
    Sturm A, Perczel A, Ivics Z, Vellai T (2017) The Piwi-piRNA pathway: road to immortality. Aging Cell 16(5):906–911. PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Taylor RC, Dillin A (2013) XBP-1 is a cell-nonautonomous regulator of stress resistance and longevity. Cell 153(7):1435–1447. PubMedPubMedCentralCrossRefGoogle Scholar
  160. 160.
    Ben-Zvi A, Miller EA, Morimoto RI (2009) Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging. Proc Natl Acad Sci USA 106(35):14914–14919. PubMedCrossRefGoogle Scholar
  161. 161.
    Nezis IP, Simonsen A, Sagona AP, Finley K, Gaumer S, Contamine D, Rusten TE, Stenmark H, Brech A (2008) Ref(2)P, the Drosophila melanogaster homologue of mammalian p62, is required for the formation of protein aggregates in adult brain. J Cell Biol 180(6):1065–1071. PubMedPubMedCentralCrossRefGoogle Scholar
  162. 162.
    Simonsen A, Cumming RC, Brech A, Isakson P, Schubert DR, Finley KD (2008) Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila. Autophagy 4(2):176–184PubMedCrossRefGoogle Scholar
  163. 163.
    Dues DJ, Andrews EK, Schaar CE, Bergsma AL, Senchuk MM, Van Raamsdonk JM (2016) Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways. Aging 8(4):777–795. PubMedPubMedCentralCrossRefGoogle Scholar
  164. 164.
    Papp D, Kovacs T, Billes V, Varga M, Tarnoci A, Hackler L Jr, Puskas LG, Liliom H, Tarnok K, Schlett K, Borsy A, Padar Z, Kovacs AL, Hegedus K, Juhasz G, Komlos M, Erdos A, Gulyas B, Vellai T (2016) AUTEN-67, an autophagy-enhancing drug candidate with potent antiaging and neuroprotective effects. Autophagy 12(2):273–286. PubMedCrossRefGoogle Scholar
  165. 165.
    Rattan SI (2006) Hormetic modulation of aging and longevity by mild heat stress. Dose Response 3(4):533–546. PubMedPubMedCentralCrossRefGoogle Scholar
  166. 166.
    Kovacs T, Billes V, Komlos M, Hotzi B, Manzeger A, Tarnoci A, Papp D, Szikszai F, Szinyakovics J, Racz A, Noszal B, Veszelka S, Walter FR, Deli MA, Hackler L Jr, Alfoldi R, Huzian O, Puskas LG, Liliom H, Tarnok K, Schlett K, Borsy A, Welker E, Kovacs AL, Padar Z, Erdos A, Legradi A, Bjelik A, Gulya K, Gulyas B, Vellai T (2017) The small molecule AUTEN-99 (autophagy enhancer-99) prevents the progression of neurodegenerative symptoms. Sci Rep 7:42014. PubMedPubMedCentralCrossRefGoogle Scholar
  167. 167.
    Billes V, Kovacs T, Hotzi B, Manzeger A, Tagscherer K, Komlos M, Tarnoci A, Padar Z, Erdos A, Bjelik A, Legradi A, Gulya K, Gulyas B, Vellai T (2016) AUTEN-67 (Autophagy Enhancer-67) hampers the progression of neurodegenerative symptoms in a Drosophila model of Huntington’s disease. J Huntingtons Dis 5(2):133–147. PubMedCrossRefGoogle Scholar
  168. 168.
    Hsu AL, Murphy CT, Kenyon C (2003) Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 300(5622):1142–1145. PubMedCrossRefGoogle Scholar
  169. 169.
    Morley JF, Morimoto RI (2004) Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones. Mol Biol Cell 15(2):657–664. PubMedPubMedCentralCrossRefGoogle Scholar
  170. 170.
    Walker GA, Thompson FJ, Brawley A, Scanlon T, Devaney E (2003) Heat shock factor functions at the convergence of the stress response and developmental pathways in Caenorhabditis elegans. FASEB J 17(13):1960–1962. PubMedCrossRefGoogle Scholar
  171. 171.
    Iser WB, Wilson MA, Wood WH 3rd, Becker K, Wolkow CA (2011) Co-regulation of the DAF-16 target gene, cyp-35B1/dod-13, by HSF-1 in C. elegans dauer larvae and daf-2 insulin pathway mutants. PLoS One 6(3):e17369. PubMedPubMedCentralCrossRefGoogle Scholar
  172. 172.
    Morrow G, Samson M, Michaud S, Tanguay RM (2004) Overexpression of the small mitochondrial Hsp22 extends Drosophila life span and increases resistance to oxidative stress. FASEB J 18(3):598–599. PubMedCrossRefGoogle Scholar
  173. 173.
    Min JN, Whaley RA, Sharpless NE, Lockyer P, Portbury AL, Patterson C (2008) CHIP deficiency decreases longevity, with accelerated aging phenotypes accompanied by altered protein quality control. Mol Cell Biol 28(12):4018–4025. PubMedPubMedCentralCrossRefGoogle Scholar
  174. 174.
    Nagarsekar A, Hasday JD, Singh IS (2005) CXC chemokines: a new family of heat-shock proteins? Immunol Investig 34(3):381–398CrossRefGoogle Scholar
  175. 175.
    Inouye S, Izu H, Takaki E, Suzuki H, Shirai M, Yokota Y, Ichikawa H, Fujimoto M, Nakai A (2004) Impaired IgG production in mice deficient for heat shock transcription factor 1. J Biol Chem 279(37):38701–38709. PubMedCrossRefGoogle Scholar
  176. 176.
    Singh V, Aballay A (2006) Heat shock and genetic activation of HSF-1 enhance immunity to bacteria. Cell Cycle 5(21):2443–2446. PubMedCrossRefGoogle Scholar
  177. 177.
    Ibrahim EC, Morange M, Dausset J, Carosella ED, Paul P (2000) Heat shock and arsenite induce expression of the nonclassical class I histocompatibility HLA-G gene in tumor cell lines. Cell Stress Chaperon 5(3):207–218CrossRefGoogle Scholar
  178. 178.
    Singh IS, He JR, Calderwood S, Hasday JD (2002) A high affinity HSF-1 binding site in the 5′-untranslated region of the murine tumor necrosis factor-alpha gene is a transcriptional repressor. J Biol Chem 277(7):4981–4988. PubMedCrossRefGoogle Scholar
  179. 179.
    Ambade A, Catalano D, Lim A, Mandrekar P (2012) Inhibition of heat shock protein (molecular weight 90 kDa) attenuates proinflammatory cytokines and prevents lipopolysaccharide-induced liver injury in mice. Hepatology 55(5):1585–1595. PubMedPubMedCentralCrossRefGoogle Scholar
  180. 180.
    Zhang L, Yang M, Wang Q, Liu M, Liang Q, Zhang H, Xiao X (2011) HSF1 regulates expression of G-CSF through the binding element for NF-IL6/CCAAT enhancer binding protein beta. Mol Cell Biochem 352(1–2):11–17. PubMedCrossRefGoogle Scholar
  181. 181.
    Xie Y, Zhong R, Chen C, Calderwood SK (2003) Heat shock factor 1 contains two functional domains that mediate transcriptional repression of the c-fos and c-fms genes. J Biol Chem 278(7):4687–4698. PubMedCrossRefGoogle Scholar
  182. 182.
    Ferat-Osorio E, Sanchez-Anaya A, Gutierrez-Mendoza M, Bosco-Garate I, Wong-Baeza I, Pastelin-Palacios R, Pedraza-Alva G, Bonifaz LC, Cortes-Reynosa P, Perez-Salazar E, Arriaga-Pizano L, Lopez-Macias C, Rosenstein Y, Isibasi A (2014) Heat shock protein 70 down-regulates the production of toll-like receptor-induced pro-inflammatory cytokines by a heat shock factor-1/constitutive heat shock element-binding factor-dependent mechanism. J Inflamm (Lond) 11:19. CrossRefGoogle Scholar
  183. 183.
    Maity TK, Henry MM, Tulapurkar ME, Shah NG, Hasday JD, Singh IS (2011) Distinct, gene-specific effect of heat shock on heat shock factor-1 recruitment and gene expression of CXC chemokine genes. Cytokine 54(1):61–67. PubMedPubMedCentralCrossRefGoogle Scholar
  184. 184.
    Rossi A, Coccia M, Trotta E, Angelini M, Santoro MG (2012) Regulation of cyclooxygenase-2 expression by heat: a novel aspect of heat shock factor 1 function in human cells. PLoS One 7(2):e31304. PubMedPubMedCentralCrossRefGoogle Scholar
  185. 185.
    Fan-xin M, Li-mei S, Bei S, Xin Q, Yu Y, Yu C (2012) Heat shock factor 1 regulates the expression of the TRPV1 gene in the rat preoptic-anterior hypothalamus area during lipopolysaccharide-induced fever. Exp Physiol 97(6):730–740. PubMedCrossRefGoogle Scholar
  186. 186.
    Hotchkiss R, Nunnally I, Lindquist S, Taulien J, Perdrizet G, Karl I (1993) Hyperthermia protects mice against the lethal effects of endotoxin. Am J Physiol 265(6 Pt 2):R1447–R1457PubMedGoogle Scholar
  187. 187.
    Jego G, Lanneau D, De Thonel A, Berthenet K, Hazoume A, Droin N, Hamman A, Girodon F, Bellaye PS, Wettstein G, Jacquel A, Duplomb L, Le Mouel A, Papanayotou C, Christians E, Bonniaud P, Lallemand-Mezger V, Solary E, Garrido C (2014) Dual regulation of SPI1/PU.1 transcription factor by heat shock factor 1 (HSF1) during macrophage differentiation of monocytes. Leukemia 28(8):1676–1686. PubMedCrossRefGoogle Scholar
  188. 188.
    Kumar M, Mitra D (2005) Heat shock protein 40 is necessary for human immunodeficiency virus-1 Nef-mediated enhancement of viral gene expression and replication. J Biol Chem 280(48):40041–40050. PubMedCrossRefGoogle Scholar
  189. 189.
    Santoro MG (1994) Heat shock proteins and virus replication: hsp70 s as mediators of the antiviral effects of prostaglandins. Experientia 50(11–12):1039–1047PubMedCrossRefGoogle Scholar
  190. 190.
    Rawat P, Mitra D (2011) Cellular heat shock factor 1 positively regulates human immunodeficiency virus-1 gene expression and replication by two distinct pathways. Nucleic Acids Res 39(14):5879–5892. PubMedPubMedCentralCrossRefGoogle Scholar
  191. 191.
    Hajdu-Cronin YM, Chen WJ, Sternberg PW (2004) The L-type cyclin CYL-1 and the heat-shock-factor HSF-1 are required for heat-shock-induced protein expression in Caenorhabditis elegans. Genetics 168(4):1937–1949. PubMedPubMedCentralCrossRefGoogle Scholar
  192. 192.
    Uchida S, Hara K, Kobayashi A, Fujimoto M, Otsuki K, Yamagata H, Hobara T, Abe N, Higuchi F, Shibata T, Hasegawa S, Kida S, Nakai A, Watanabe Y (2011) Impaired hippocampal spinogenesis and neurogenesis and altered affective behavior in mice lacking heat shock factor 1. Proc Natl Acad Sci USA 108(4):1681–1686. PubMedCrossRefGoogle Scholar
  193. 193.
    Varodayan FP, Harrison NL (2013) HSF1 transcriptional activity mediates alcohol induction of Vamp2 expression and GABA release. Front Integr Neurosci 7:89. PubMedPubMedCentralCrossRefGoogle Scholar
  194. 194.
    Varodayan FP, Pignataro L, Harrison NL (2011) Alcohol induces synaptotagmin 1 expression in neurons via activation of heat shock factor 1. Neurosci 193:63–71. CrossRefGoogle Scholar
  195. 195.
    Tan J, Tan S, Zheng H, Liu M, Chen G, Zhang H, Wang K, Zhou J, Xiao XZ (2015) HSF1 functions as a transcription regulator for Dp71 expression. Cell Stress Chaperon 20(2):371–379. CrossRefGoogle Scholar
  196. 196.
    Takaki E, Fujimoto M, Sugahara K, Nakahari T, Yonemura S, Tanaka Y, Hayashida N, Inouye S, Takemoto T, Yamashita H, Nakai A (2006) Maintenance of olfactory neurogenesis requires HSF1, a major heat shock transcription factor in mice. J Biol Chem 281(8):4931–4937. PubMedCrossRefGoogle Scholar
  197. 197.
    Fujimoto M, Izu H, Seki K, Fukuda K, Nishida T, Yamada S, Kato K, Yonemura S, Inouye S, Nakai A (2004) HSF4 is required for normal cell growth and differentiation during mouse lens development. EMBO J 23(21):4297–4306. PubMedPubMedCentralCrossRefGoogle Scholar
  198. 198.
    Izu H, Inouye S, Fujimoto M, Shiraishi K, Naito K, Nakai A (2004) Heat shock transcription factor 1 is involved in quality-control mechanisms in male germ cells. Biol Rep 70(1):18–24. CrossRefGoogle Scholar
  199. 199.
    Widlak W, Benedyk K, Vydra N, Glowala M, Scieglinska D, Malusecka E, Nakai A, Krawczyk Z (2003) Expression of a constitutively active mutant of heat shock factor 1 under the control of testis-specific hst70 gene promoter in transgenic mice induces degeneration of seminiferous epithelium. Acta Biochim Polon 50(2):535–541PubMedGoogle Scholar
  200. 200.
    Metchat A, Akerfelt M, Bierkamp C, Delsinne V, Sistonen L, Alexandre H, Christians ES (2009) Mammalian heat shock factor 1 is essential for oocyte meiosis and directly regulates Hsp90alpha expression. J Biol Chem 284(14):9521–9528. PubMedPubMedCentralCrossRefGoogle Scholar
  201. 201.
    Le Masson F, Razak Z, Kaigo M, Audouard C, Charry C, Cooke H, Westwood JT, Christians ES (2011) Identification of heat shock factor 1 molecular and cellular targets during embryonic and adult female meiosis. Mol Cell Biol 31(16):3410–3423. PubMedPubMedCentralCrossRefGoogle Scholar
  202. 202.
    Leise TL, Wang CW, Gitis PJ, Welsh DK (2012) Persistent cell-autonomous circadian oscillations in fibroblasts revealed by six-week single-cell imaging of PER2:LUC bioluminescence. PLoS One 7(3):e33334. PubMedPubMedCentralCrossRefGoogle Scholar
  203. 203.
    Saini C, Morf J, Stratmann M, Gos P, Schibler U (2012) Simulated body temperature rhythms reveal the phase-shifting behavior and plasticity of mammalian circadian oscillators. Genes Dev 26(6):567–580. PubMedPubMedCentralCrossRefGoogle Scholar
  204. 204.
    Tamaru T, Hattori M, Honda K, Benjamin I, Ozawa T, Takamatsu K (2011) Synchronization of circadian Per2 rhythms and HSF1-BMAL1:CLOCK interaction in mouse fibroblasts after short-term heat shock pulse. PLoS One 6(9):e24521. PubMedPubMedCentralCrossRefGoogle Scholar
  205. 205.
    Kornmann B, Schaad O, Bujard H, Takahashi JS, Schibler U (2007) System-driven and oscillator-dependent circadian transcription in mice with a conditionally active liver clock. PLoS Biol 5(2):e34. PubMedPubMedCentralCrossRefGoogle Scholar
  206. 206.
    Reinke H, Saini C, Fleury-Olela F, Dibner C, Benjamin IJ, Schibler U (2008) Differential display of DNA-binding proteins reveals heat-shock factor 1 as a circadian transcription factor. Genes Dev 22(3):331–345. PubMedPubMedCentralCrossRefGoogle Scholar
  207. 207.
    Hatori M, Hirota T, Iitsuka M, Kurabayashi N, Haraguchi S, Kokame K, Sato R, Nakai A, Miyata T, Tsutsui K, Fukada Y (2011) Light-dependent and circadian clock-regulated activation of sterol regulatory element-binding protein, X-box-binding protein 1, and heat shock factor pathways. Proc Natl Acad Sci USA 108(12):4864–4869. PubMedCrossRefGoogle Scholar
  208. 208.
    Tóth ML, Sigmond T, Borsos E, Barna J, Erdélyi P, Takács-Vellai K, Orosz L, Kovács AL, Csikós G, Sass M, Vellai T (2008) Longevity pathways converge on autophagy genes to regulate life span in Caenorhabditis elegans. Autophagy 4(3):330–338PubMedCrossRefGoogle Scholar
  209. 209.
    Vellai T, Bicsák B, Tóth ML, Takács-Vellai K, Kovács AL (2008) Regulation of cell growth by autophagy. Autophagy 4(4):507–509PubMedCrossRefGoogle Scholar
  210. 210.
    Baird NA, Douglas PM, Simic MS, Grant AR, Moresco JJ, Wolff SC, Yates JR 3rd, Manning G, Dillin A (2014) HSF-1-mediated cytoskeletal integrity determines thermotolerance and life span. Science 346(6207):360–363. PubMedPubMedCentralCrossRefGoogle Scholar
  211. 211.
    Verma P, Pfister JA, Mallick S, D’Mello SR (2014) HSF1 protects neurons through a novel trimerization- and HSP-independent mechanism. J Neurosci 34(5):1599–1612. PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of GeneticsEötvös Loránd UniversityBudapestHungary
  2. 2.MTA-ELTE Genetics Research GroupEötvös Loránd UniversityBudapestHungary
  3. 3.Department of Medical ChemistrySemmelweis UniversityBudapestHungary

Personalised recommendations