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Gene Review

Hsf1  -  heat shock factor 1

Mus musculus

Synonyms: AA960185, HSF 1, HSTF 1, Heat shock factor protein 1, Heat shock transcription factor 1, ...
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Disease relevance of Hsf1


High impact information on Hsf1


Chemical compound and disease context of Hsf1


Biological context of Hsf1

  • Using Hsf1-/- cells, we show that this factor is responsible for targeting histone H4 acetylation to Hsp70 chromatin [9].
  • Using multiple Ag systems, we demonstrated that cross-priming of Ag-specific CD8+ T cells was inefficient when Ag expression was restricted to Hsf1(-/-) non-APCs [10].
  • Hsf1-/- mice and their normal littermates (Hsf1+/+) were exposed to a 98-dB, broadband (2-20 kHz) noise for 2 hr, and auditory brainstem response thresholds were measured at three frequencies (4, 12, and 20 kHz) 3 hr, 3 days, and 2 weeks after noise [1].
  • Mammalian heat shock factor 1 (Hsf1), which binds conserved sequences on the promoter of the hsp70 gene when cells are exposed to various stress stimuli, utilizes Brg1-SWI/SNF complexes and stimulates transcription in vitro at the level of initiation and elongation [11].
  • Thus, the present study demonstrates that Hsf1-dependent transcription of selective Hsps is required for normal renal homeostasis, which protects renal cells against oxidative stress under physiological conditions [4].

Anatomical context of Hsf1

  • However, we show here that geldanamycin blocks the development of aggregates of the expanded glutamine androgen receptor (AR112Q) of Kennedy disease in Hsf1(-/-) mouse embryonic fibroblasts where these chaperones are not induced [12].
  • We previously demonstrated the presence of Hsf1 in the rodent cochlea and also demonstrated that a heat shock known to precondition the cochlea against noise trauma results in Hsf1 activation in the rodent cochlea [1].
  • Increased outer hair cell loss was also observed in Hsf1-/- mice following noise [1].
  • We found that the loss of sensory hair cells was more significant in HSF1-null mice compared with that of wild-type mice when mice were subjected to acoustic overexposure [13].
  • HSF1 disruption also increased mitochondrial permeability transition pore opening and induced greater mitochondrial membrane potential change (48% increase versus wild type) [4].

Associations of Hsf1 with chemical compounds


Physical interactions of Hsf1


Regulatory relationships of Hsf1


Other interactions of Hsf1

  • Among the three known mammalian Hsfs, Hsf1 is recognized as the most effective transactivator of Hsps in response to thermal challenge, but the role of Hsf2 in regulation of genes under normal or increased stress conditions in vivo remains elusive [25].
  • All three mammalian HSFs (HSF1, HSF2, HSF4) have also been shown to be required for normal mammalian development [26].
  • However, independently of p38 MAP kinase, both stresses strongly activate the transcription factor Hsf1 [9].
  • Con sequently, superoxide was generated at a higher rate, and several mitochondrial proteins, including adenine nucleotide translocase 1 (ANT1), were more oxidized by HSF1 deficiency in vivo [27].
  • Immune complex kinase assays of heat shocked or SV-pretreated cells indicated that HSF-1 is a potential in vivo substrate for ERK1 phosphorylation [28].

Analytical, diagnostic and therapeutic context of Hsf1


  1. Heat shock factor 1-deficient mice exhibit decreased recovery of hearing following noise overstimulation. Fairfield, D.A., Lomax, M.I., Dootz, G.A., Chen, S., Galecki, A.T., Benjamin, I.J., Dolan, D.F., Altschuler, R.A. J. Neurosci. Res. (2005) [Pubmed]
  2. Targeted disruption of hsf1 leads to lack of thermotolerance and defines tissue-specific regulation for stress-inducible Hsp molecular chaperones. Zhang, Y., Huang, L., Zhang, J., Moskophidis, D., Mivechi, N.F. J. Cell. Biochem. (2002) [Pubmed]
  3. Heat shock transcription factor (HSF1) plays a critical role in cell migration via maintaining MAP kinase signaling. O'Callaghan-Sunol, C., Sherman, M.Y. Cell Cycle (2006) [Pubmed]
  4. Mouse HSF1 disruption perturbs redox state and increases mitochondrial oxidative stress in kidney. Yan, L.J., Rajasekaran, N.S., Sathyanarayanan, S., Benjamin, I.J. Antioxid. Redox Signal. (2005) [Pubmed]
  5. Structural organization and promoter analysis of murine heat shock transcription factor-1 gene. Zhang, Y., Koushik, S., Dai, R., Mivechi, N.F. J. Biol. Chem. (1998) [Pubmed]
  6. Redox regulation of mammalian heat shock factor 1 is essential for Hsp gene activation and protection from stress. Ahn, S.G., Thiele, D.J. Genes Dev. (2003) [Pubmed]
  7. The loop domain of heat shock transcription factor 1 dictates DNA-binding specificity and responses to heat stress. Ahn, S.G., Liu, P.C., Klyachko, K., Morimoto, R.I., Thiele, D.J. Genes Dev. (2001) [Pubmed]
  8. Glutamine's protection against cellular injury is dependent on heat shock factor-1. Morrison, A.L., Dinges, M., Singleton, K.D., Odoms, K., Wong, H.R., Wischmeyer, P.E. Am. J. Physiol., Cell Physiol. (2006) [Pubmed]
  9. Distinct stimulus-specific histone modifications at hsp70 chromatin targeted by the transcription factor heat shock factor-1. Thomson, S., Hollis, A., Hazzalin, C.A., Mahadevan, L.C. Mol. Cell (2004) [Pubmed]
  10. Cutting edge: cross-presentation of cell-associated antigens to MHC class I molecule is regulated by a major transcription factor for heat shock proteins. Zheng, H., Li, Z. J. Immunol. (2004) [Pubmed]
  11. Heat shock transcription factor (Hsf)-4b recruits Brg1 during the G1 phase of the cell cycle and regulates the expression of heat shock proteins. Tu, N., Hu, Y., Mivechi, N.F. J. Cell. Biochem. (2006) [Pubmed]
  12. Pharmacologic and genetic inhibition of hsp90-dependent trafficking reduces aggregation and promotes degradation of the expanded glutamine androgen receptor without stress protein induction. Thomas, M., Harrell, J.M., Morishima, Y., Peng, H.M., Pratt, W.B., Lieberman, A.P. Hum. Mol. Genet. (2006) [Pubmed]
  13. Heat shock transcription factor HSF1 is required for survival of sensory hair cells against acoustic overexposure. Sugahara, K., Inouye, S., Izu, H., Katoh, Y., Katsuki, K., Takemoto, T., Shimogori, H., Yamashita, H., Nakai, A. Hear. Res. (2003) [Pubmed]
  14. Evidence for a role of heat shock factor 1 in inhibition of NF-kappaB pathway during heat shock response-mediated lung protection. Wirth, D., Bureau, F., Melotte, D., Christians, E., Gustin, P. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  15. Heat shock protein 25 or inducible heat shock protein 70 activates heat shock factor 1: dephosphorylation on serine 307 through inhibition of ERK1/2 phosphorylation. Seo, H.R., Chung, D.Y., Lee, Y.J., Lee, D.H., Kim, J.I., Bae, S., Chung, H.Y., Lee, S.J., Jeoung, D., Lee, Y.S. J. Biol. Chem. (2006) [Pubmed]
  16. Estrogen dependent expression of heat shock transcription factor: implications for uterine synthesis of heat shock proteins. Yang, X., Dale, E.C., Diaz, J., Shyamala, G. J. Steroid Biochem. Mol. Biol. (1995) [Pubmed]
  17. Activation of heat shock gene transcription by heat shock factor 1 involves oligomerization, acquisition of DNA-binding activity, and nuclear localization and can occur in the absence of stress. Sarge, K.D., Murphy, S.P., Morimoto, R.I. Mol. Cell. Biol. (1993) [Pubmed]
  18. Phenotypic characterization of mouse embryonic fibroblasts lacking heat shock factor 2. Paslaru, L., Morange, M., Mezger, V. J. Cell. Mol. Med. (2003) [Pubmed]
  19. Heat shock-induced dendritic cell maturation is coupled by transient aggregation of ubiquitinated proteins independently of heat shock factor 1 or inducible heat shock protein 70. DeFillipo, A.M., Dai, J., Li, Z. Mol. Immunol. (2004) [Pubmed]
  20. Differential regulation of activator protein-1 and heat shock factor-1 in myocardial ischemia and reperfusion injury: role of poly(ADP-ribose) polymerase-1. Zingarelli, B., Hake, P.W., O'Connor, M., Denenberg, A., Wong, H.R., Kong, S., Aronow, B.J. Am. J. Physiol. Heart Circ. Physiol. (2004) [Pubmed]
  21. Heat-induced transcription from RNA polymerases II and III and HSF binding activity are co-ordinately regulated by the products of the heat shock genes. Price, B.D., Calderwood, S.K. J. Cell. Physiol. (1992) [Pubmed]
  22. Transcriptional activity of heat shock factor 1 at 37 degrees C is repressed through phosphorylation on two distinct serine residues by glycogen synthase kinase 3 and protein kinases Calpha and Czeta. Chu, B., Zhong, R., Soncin, F., Stevenson, M.A., Calderwood, S.K. J. Biol. Chem. (1998) [Pubmed]
  23. Enlarged ventricles, astrogliosis and neurodegeneration in heat shock factor 1 null mouse brain. Santos, S.D., Saraiva, M.J. Neuroscience (2004) [Pubmed]
  24. Heat shock-mediated regulation of MKP-1. Wong, H.R., Dunsmore, K.E., Page, K., Shanley, T.P. Am. J. Physiol., Cell Physiol. (2005) [Pubmed]
  25. Targeted disruption of the heat shock transcription factor (hsf)-2 gene results in increased embryonic lethality, neuronal defects, and reduced spermatogenesis. Wang, G., Zhang, J., Moskophidis, D., Mivechi, N.F. Genesis (2003) [Pubmed]
  26. Heat shock factor 1 is required for constitutive Hsp70 expression and normal lens development in embryonic zebrafish. Evans, T.G., Belak, Z., Ovsenek, N., Krone, P.H. Comp. Biochem. Physiol., Part A Mol. Integr. Physiol. (2007) [Pubmed]
  27. Mouse heat shock transcription factor 1 deficiency alters cardiac redox homeostasis and increases mitochondrial oxidative damage. Yan, L.J., Christians, E.S., Liu, L., Xiao, X., Sohal, R.S., Benjamin, I.J. EMBO J. (2002) [Pubmed]
  28. Mitogen-activated protein kinase acts as a negative regulator of the heat shock response in NIH3T3 cells. Mivechi, N.F., Giaccia, A.J. Cancer Res. (1995) [Pubmed]
  29. Heat shock response: lessons from mouse knockouts. Christians, E.S., Benjamin, I.J. Handbook of experimental pharmacology. (2006) [Pubmed]
  30. Stimulation of the stress-induced expression of stress proteins by curcumin in cultured cells and in rat tissues in vivo. Kato, K., Ito, H., Kamei, K., Iwamoto, I. Cell Stress Chaperones (1998) [Pubmed]
  31. Use of Hsf1(-/-) mice reveals an essential role for HSF1 to protect lung against cadmium-induced injury. Wirth, D., Christians, E., Li, X., Benjamin, I.J., Gustin, P. Toxicol. Appl. Pharmacol. (2003) [Pubmed]
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