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2
* Turku Centre for Biotechnology, University of Turku and Åbo Akademi University; and
Department of Biology, Åbo Akademi University, Turku, Finland
2Correspondence: Turku Centre for Biotechnology, Tykistokaty 6B, 20521 Turku, Finland. E-mail lea.sistonen{at}btk.utu.fi
The heat shock response, characterized by increased expression of heat shock proteins (Hsps) is induced by exposure of cells and tissues to extreme conditions that cause acute or chronic stress. Hsps function as molecular chaperones in regulating cellular homeostasis and promoting survival. If the stress is too severe, a signal that leads to programmed cell death, apoptosis, is activated, thereby providing a finely tuned balance between survival and death. In addition to extracellular stimuli, several nonstressful conditions induce Hsps during normal cellular growth and development. The enhanced heat shock gene expression in response to various stimuli is regulated by heat shock transcription factors (HSFs). After the discovery of the family of HSFs (i.e., murine and human HSF1, 2, and 4 and a unique avian HSF3), the functional relevance of distinct HSFs is now emerging. HSF1, an HSF prototype, and HSF3 are responsible for heat-induced Hsp expression, whereas HSF2 is refractory to classical stressors. HSF4 is expressed in a tissue-specific manner; similar to HSF1 and HSF2, alternatively spliced isoforms add further complexity to its regulation. Recently developed powerful genetic models have provided evidence for both cooperative and specific functions of HSFs that expand beyond the heat shock response. Certain specialized functions of HSFs may even include regulation of novel target genes in response to distinct stimuli.—Pirkkala, L., Nykänen, P, Sistonen, L. Roles of the heat shock transcription factors in regulation of the heat shock response and beyond.
Key Words: heat shock element • hsps • HSF family • knockout and transgenic HSF models
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 B. A. Buckley, S. P. Place, and G. E. Hofmann Regulation of heat shock genes in isolated hepatocytes from an Antarctic fish, Trematomus bernacchii J. Exp. Biol., October 1, 2004; 207(21): 3649 - 3656. [Abstract] [Full Text] [PDF]
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 A. Metz, J. Soret, C. Vourc'h, J. Tazi, and C. Jolly A key role for stress-induced satellite III transcripts in the relocalization of splicing factors into nuclear stress granules J. Cell Sci., September 1, 2004; 117(19): 4551 - 4558. [Abstract] [Full Text] [PDF]
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S. Izawa, R. Takemura, and Y. Inoue Gle2p Is Essential to Induce Adaptation of the Export of Bulk Poly(A)+ mRNA to Heat Shock in Saccharomyces cerevisiae J. Biol. Chem., August 20, 2004; 279(34): 35469 - 35478. [Abstract] [Full Text] [PDF]
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I. Chiodi, M. Corioni, M. Giordano, R. Valgardsdottir, C. Ghigna, F. Cobianchi, R.-M. Xu, S. Riva, and G. Biamonti RNA recognition motif 2 directs the recruitment of SF2/ASF to nuclear stress bodies Nucleic Acids Res., August 9, 2004; 32(14): 4127 - 4136. [Abstract] [Full Text] [PDF]
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 N. Smaoui, O. Beltaief, S. BenHamed, R. M'Rad, F. Maazoul, A. Ouertani, H. Chaabouni, and J. F. Hejtmancik A Homozygous Splice Mutation in the HSF4 Gene Is Associated with an Autosomal Recessive Congenital Cataract Invest. Ophthalmol. Vis. Sci., August 1, 2004; 45(8): 2716 - 2721. [Abstract] [Full Text] [PDF]
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T. Kawai, J. Fan, K. Mazan-Mamczarz, and M. Gorospe Global mRNA Stabilization Preferentially Linked to Translational Repression during the Endoplasmic Reticulum Stress Response Mol. Cell. Biol., August 1, 2004; 24(15): 6773 - 6787. [Abstract] [Full Text] [PDF]
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N. E. Zachara, N. O'Donnell, W. D. Cheung, J. J. Mercer, J. D. Marth, and G. W. Hart Dynamic O-GlcNAc Modification of Nucleocytoplasmic Proteins in Response to Stress: A SURVIVAL RESPONSE OF MAMMALIAN CELLS J. Biol. Chem., July 16, 2004; 279(29): 30133 - 30142. [Abstract] [Full Text] [PDF]
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S. M. Myers and L. M. Mulligan The RET Receptor Is Linked to Stress Response Pathways Cancer Res., July 1, 2004; 64(13): 4453 - 4463. [Abstract] [Full Text] [PDF]
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S. Fu and M. J. Scanlon Clonal Mosaic Analysis of EMPTY PERICARP2 Reveals Nonredundant Functions of the Duplicated HEAT SHOCK FACTOR BINDING PROTEINs During Maize Shoot Development Genetics, July 1, 2004; 167(3): 1381 - 1394. [Abstract] [Full Text] [PDF]
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 T. Shinka, Y. Sato, G. Chen, T. Naroda, K. Kinoshita, Y. Unemi, K. Tsuji, K. Toida, T. Iwamoto, and Y. Nakahori Molecular Characterization of Heat Shock-Like Factor Encoded on the Human Y Chromosome, and Implications for Male Infertility Biol Reprod, July 1, 2004; 71(1): 297 - 306. [Abstract] [Full Text] [PDF]
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K. M. Bohren, V. Nadkarni, J. H. Song, K. H. Gabbay, and D. Owerbach A M55V Polymorphism in a Novel SUMO Gene (SUMO-4) Differentially Activates Heat Shock Transcription Factors and Is Associated with Susceptibility to Type I Diabetes Mellitus J. Biol. Chem., June 25, 2004; 279(26): 27233 - 27238. [Abstract] [Full Text] [PDF]
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J.-S. Hahn, Z. Hu, D. J. Thiele, and V. R. Iyer Genome-Wide Analysis of the Biology of Stress Responses through Heat Shock Transcription Factor Mol. Cell. Biol., June 15, 2004; 24(12): 5249 - 5256. [Abstract] [Full Text] [PDF]
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 I. S. Singh, J.-R. He, L. Hester, M. J. Fenton, and J. D. Hasday Bacterial endotoxin modifies heat shock factor-1 activity in RAW 264.7 cells: implications for TNF-{alpha} regulation during exposure to febrile range temperatures Innate Immunity, June 1, 2004; 10(3): 175 - 184. [Abstract] [PDF]
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M. T. Fiorenza, A. Bevilacqua, S. Canterini, S. Torcia, M. Pontecorvi, and F. Mangia Early Transcriptional Activation of the Hsp70.1 Gene by Osmotic Stress in One-Cell Embryos of the Mouse Biol Reprod, June 1, 2004; 70(6): 1606 - 1613. [Abstract] [Full Text] [PDF]
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N. Hashikawa and H. Sakurai Phosphorylation of the Yeast Heat Shock Transcription Factor Is Implicated in Gene-Specific Activation Dependent on the Architecture of the Heat Shock Element Mol. Cell. Biol., May 1, 2004; 24(9): 3648 - 3659. [Abstract] [Full Text] [PDF]
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 A. Tessari, E. Salata, A. Ferlin, L. Bartoloni, M.L. Slongo, and C. Foresta Characterization of HSFY, a novel AZFb gene on the Y chromosome with a possible role in human spermatogenesis Mol. Hum. Reprod., April 1, 2004; 10(4): 253 - 258. [Abstract] [Full Text] [PDF]
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F. Boellmann, T. Guettouche, Y. Guo, M. Fenna, L. Mnayer, and R. Voellmy DAXX interacts with heat shock factor 1 during stress activation and enhances its transcriptional activity PNAS, March 23, 2004; 101(12): 4100 - 4105. [Abstract] [Full Text] [PDF]
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H. Xing, C. N. Mayhew, K. E. Cullen, O.-K. Park-Sarge, and K. D. Sarge HSF1 Modulation of Hsp70 mRNA Polyadenylation via Interaction with Symplekin J. Biol. Chem., March 12, 2004; 279(11): 10551 - 10555. [Abstract] [Full Text] [PDF]
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N. D. Trinklein, J. I. Murray, S. J. Hartman, D. Botstein, and R. M. Myers The Role of Heat Shock Transcription Factor 1 in the Genome-wide Regulation of the Mammalian Heat Shock Response Mol. Biol. Cell, March 1, 2004; 15(3): 1254 - 1261. [Abstract] [Full Text] [PDF]
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J.-S. Hahn and D. J. Thiele Activation of the Saccharomyces cerevisiae Heat Shock Transcription Factor Under Glucose Starvation Conditions by Snf1 Protein Kinase J. Biol. Chem., February 13, 2004; 279(7): 5169 - 5176. [Abstract] [Full Text] [PDF]
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 D. M. Katschinski On Heat and Cells and Proteins Physiology, February 1, 2004; 19(1): 11 - 15. [Abstract] [Full Text] [PDF]
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 C. Jolly, A. Metz, J. Govin, M. Vigneron, B. M. Turner, S. Khochbin, and C. Vourc'h Stress-induced transcription of satellite III repeats J. Cell Biol., January 5, 2004; 164(1): 25 - 33. [Abstract] [Full Text] [PDF]
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A. Sandqvist and L. Sistonen Nuclear stress granules: the awakening of a sleeping beauty? J. Cell Biol., January 5, 2004; 164(1): 15 - 17. [Abstract] [Full Text] [PDF]
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