The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

HSF2  -  heat shock transcription factor 2

Homo sapiens

Synonyms: HSF 2, HSTF 2, HSTF2, Heat shock factor protein 2, Heat shock transcription factor 2
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of HSF2

  • HSF1 is activated by heat shock and other forms of stress, whereas HSF2 is activated during hemin-induced differentiation of human K562 erythroleukemia cells, suggesting a role for HSF2 in regulating heat shock gene expression under nonstress conditions such as differentiation and development [1].
  • In contrast, HSF2 is not activated by heat stress and has been speculated to have developmental functions [2].
  • Furthermore, while quercetin treatment inhibited HSF2 expression, it only slightly affected HSF1 expression in breast cancer cells [3].
  • HSF1 transcriptional activity has been discussed in neuronal cells, concentrating on the regulation and activity of HSF1 and HSF2 and their role in HSP expression, during neurodegenerative diseases and as mediators of cell survival [4].

High impact information on HSF2

  • Here, we show that point mutations in either of two amino-terminal zippers or in the carboxy-terminal zipper disrupt normal localization of HSF2 and cause it to be constitutively nuclear [5].
  • Expression of HSP-70, HSF1, and HSF2 genes and protein were determined [6].
  • Moreover, hHSF1 and hHSF2 exhibit selectivity for transcriptional activation of two distinct yeast heat shock responsive genes, which correlate with previously established mammalian HSF DNA binding preferences in vitro [7].
  • Hence, SUMO modification of the HSF2 loop contributes to HSF-specific regulation of DNA binding and broadens the concept of sumoylation in the negative regulation of gene expression [8].
  • We demonstrate that enhanced HSF2 expression and the acquisition of HSF2 DNA binding activity are strictly specific for erythroid characteristics of K562 cells [9].

Biological context of HSF2

  • We show here that a chimeric polypeptide of HSF2 and GAL4 DNA binding domain (GAL4-BD-HSF2) was unable to induce a GAL4 binding site-containing luciferase reporter gene in response to hemin and that exogenously overproduced HSF2 also failed to increase expression of a heat shock element-containing reporter [10].
  • In addition, HSF2 regulation involves differential activity of two isoforms, HSF2A and HSF2B, which arise from alternative splicing of a common hsf2 gene [11].
  • Although heat shock factor 2 (HSF2) binds to heat shock element (HSE) constitutively during differentiation, development and spermatogenesis, little is known about the nature and mechanism of transcriptional control of heat shock genes by HSF2 [12].
  • This is the first demonstration that HSF2 can be activated by KCl and is involved in the upregulation of alphaB-crystallin gene expression in glial cells [13].
  • Recent reports have suggested that both HSF1 and HSF2 are affected during down-regulation of ubiquitin-proteasome pathway (Y. Kawazoe et al., Eur. J. Biochem. 255:356-362, 1998; A. Mathew et al., Mol. Cell. Biol. 18:5091-5098, 1998; D. Kim et al., Biochem. Biophys. Res. Commun. 254:264-268, 1999) [14].

Anatomical context of HSF2

  • Our results reveal that the inactive, non-DNA-binding forms of HSF2 and HSF1 exist primarily in the cytoplasm of untreated K562 cells as a dimer and monomer, respectively [1].
  • Using these tools, we have shown that human HeLa cells constitutively synthesize HSF1, but we were unable to detect HSF2 [15].
  • HSF2BP may therefore be involved in modulating HSF2 activation in testis [12].
  • In contrast, strong Hsp70 induction occurred in motor neurons with expression of a constitutively active form of heat shock transcription factor (HSF)-1 or when proteasome activity was sufficiently inhibited to induce accumulation of an alternative transcription factor HSF2 [16].
  • These results demonstrate that ROS stimulates RANKL expression via ERKs and PKA-CREB pathway in mouse osteoblasts and via ERKs and HSF2 in human MG63 cells [17].

Associations of HSF2 with chemical compounds

  • Our results identify lysine 82 as the major site of SUMO-1 modification in HSF2, which is located in a "wing" within the DNA-binding domain of this protein [18].

Physical interactions of HSF2


Regulatory relationships of HSF2


Other interactions of HSF2

  • We report here that hemin activates the DNA-binding activity of HSF2, whereas heat shock induces predominantly the DNA-binding activity of a distinct factor, HSF1 [24].
  • Interestingly, SUMO-1 modification of HSF2 results in conversion of this factor to the active DNA binding form [18].
  • These results indicate that HSF1, rather than HSF2, primarily mediates the hemin-induced transcription of the hsp70 gene [10].
  • Staining with anti-promyelocytic leukemia antibodies indicates that these HSF2-containing nuclear granules are PML bodies [18].
  • These data suggest the possibility that p62 is involved in the activation or regulation of HSF2 [25].

Analytical, diagnostic and therapeutic context of HSF2


  1. Human heat shock factors 1 and 2 are differentially activated and can synergistically induce hsp70 gene transcription. Sistonen, L., Sarge, K.D., Morimoto, R.I. Mol. Cell. Biol. (1994) [Pubmed]
  2. HSF3 is a major heat shock responsive factor duringchicken embryonic development. Kawazoe, Y., Tanabe, M., Sasai, N., Nagata, K., Nakai, A. Eur. J. Biochem. (1999) [Pubmed]
  3. Quercetin inhibits heat shock protein induction but not heat shock factor DNA-binding in human breast carcinoma cells. Hansen, R.K., Oesterreich, S., Lemieux, P., Sarge, K.D., Fuqua, S.A. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  4. Regulation of heat shock gene transcription in neuronal cells. Tonkiss, J., Calderwood, S.K. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group. (2005) [Pubmed]
  5. Hydrophobic coiled-coil domains regulate the subcellular localization of human heat shock factor 2. Sheldon, L.A., Kingston, R.E. Genes Dev. (1993) [Pubmed]
  6. Heat shock factor-1 protein in heat shock factor-1 gene-transfected human epidermoid A431 cells requires phosphorylation before inducing heat shock protein-70 production. Ding, X.Z., Tsokos, G.C., Kiang, J.G. J. Clin. Invest. (1997) [Pubmed]
  7. Conservation of a stress response: human heat shock transcription factors functionally substitute for yeast HSF. Liu, X.D., Liu, P.C., Santoro, N., Thiele, D.J. EMBO J. (1997) [Pubmed]
  8. Inhibition of DNA binding by differential sumoylation of heat shock factors. Anckar, J., Hietakangas, V., Denessiouk, K., Thiele, D.J., Johnson, M.S., Sistonen, L. Mol. Cell. Biol. (2006) [Pubmed]
  9. Differentiation lineage-specific expression of human heat shock transcription factor 2. Pirkkala, L., Alastalo, T.P., Nykanen, P., Seppa, L., Sistonen, L. FASEB J. (1999) [Pubmed]
  10. Heat shock factor 1 mediates hemin-induced hsp70 gene transcription in K562 erythroleukemia cells. Yoshima, T., Yura, T., Yanagi, H. J. Biol. Chem. (1998) [Pubmed]
  11. Elevated expression of heat shock factor (HSF) 2A stimulates HSF1-induced transcription during stress. He, H., Soncin, F., Grammatikakis, N., Li, Y., Siganou, A., Gong, J., Brown, S.A., Kingston, R.E., Calderwood, S.K. J. Biol. Chem. (2003) [Pubmed]
  12. Novel testis-specific protein that interacts with heat shock factor 2. Yoshima, T., Yura, T., Yanagi, H. Gene (1998) [Pubmed]
  13. Heat shock factor 2 is involved in the upregulation of alphaB-crystallin by high extracellular potassium. Sadamitsu, C., Nagano, T., Fukumaki, Y., Iwaki, A. J. Biochem. (2001) [Pubmed]
  14. Disruption of heat shock factor 1 reveals an essential role in the ubiquitin proteolytic pathway. Pirkkala, L., Alastalo, T.P., Zuo, X., Benjamin, I.J., Sistonen, L. Mol. Cell. Biol. (2000) [Pubmed]
  15. Activation of human heat shock genes is accompanied by oligomerization, modification, and rapid translocation of heat shock transcription factor HSF1. Baler, R., Dahl, G., Voellmy, R. Mol. Cell. Biol. (1993) [Pubmed]
  16. High threshold for induction of the stress response in motor neurons is associated with failure to activate HSF1. Batulan, Z., Shinder, G.A., Minotti, S., He, B.P., Doroudchi, M.M., Nalbantoglu, J., Strong, M.J., Durham, H.D. J. Neurosci. (2003) [Pubmed]
  17. Reactive oxygen species stimulates receptor activator of NF-kappaB ligand expression in osteoblast. Bai, X.C., Lu, D., Liu, A.L., Zhang, Z.M., Li, X.M., Zou, Z.P., Zeng, W.S., Cheng, B.L., Luo, S.Q. J. Biol. Chem. (2005) [Pubmed]
  18. Sumo-1 modification regulates the DNA binding activity of heat shock transcription factor 2, a promyelocytic leukemia nuclear body associated transcription factor. Goodson, M.L., Hong, Y., Rogers, R., Matunis, M.J., Park-Sarge, O.K., Sarge, K.D. J. Biol. Chem. (2001) [Pubmed]
  19. Formation of nuclear stress granules involves HSF2 and coincides with the nucleolar localization of Hsp70. Alastalo, T.P., Hellesuo, M., Sandqvist, A., Hietakangas, V., Kallio, M., Sistonen, L. J. Cell. Sci. (2003) [Pubmed]
  20. Heat shock factor 1 contains two functional domains that mediate transcriptional repression of the c-fos and c-fms genes. Xie, Y., Zhong, R., Chen, C., Calderwood, S.K. J. Biol. Chem. (2003) [Pubmed]
  21. Overexpression of HSF2-beta inhibits hemin-induced heat shock gene expression and erythroid differentiation in K562 cells. Leppä, S., Pirkkala, L., Saarento, H., Sarge, K.D., Sistonen, L. J. Biol. Chem. (1997) [Pubmed]
  22. Thioredoxin is transcriptionally induced upon activation of heat shock factor 2. Leppä, S., Pirkkala, L., Chow, S.C., Eriksson, J.E., Sistonen, L. J. Biol. Chem. (1997) [Pubmed]
  23. MEL-18 interacts with HSF2 and the SUMO E2 UBC9 to inhibit HSF2 sumoylation. Zhang, J., Goodson, M.L., Hong, Y., Sarge, K.D. J. Biol. Chem. (2008) [Pubmed]
  24. Activation of heat shock factor 2 during hemin-induced differentiation of human erythroleukemia cells. Sistonen, L., Sarge, K.D., Phillips, B., Abravaya, K., Morimoto, R.I. Mol. Cell. Biol. (1992) [Pubmed]
  25. The trimerization domain of human heat shock factor 2 is able to interact with nucleoporin p62. Yoshima, T., Yura, T., Yanagi, H. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  26. Determination of heat-shock transcription factor 2 stoichiometry at looped DNA complexes using scanning force microscopy. Wyman, C., Grotkopp, E., Bustamante, C., Nelson, H.C. EMBO J. (1995) [Pubmed]
  27. Human aging alters the first phase of the molecular response to stress in T-cells. Jurivich, D.A., Choo, M., Welk, J., Qiu, L., Han, K., Zhou, X. Exp. Gerontol. (2005) [Pubmed]
  28. Developmentally dictated expression of heat shock factors: exclusive expression of HSF4 in the postnatal lens and its specific interaction with alphaB-crystallin heat shock promoter. Somasundaram, T., Bhat, S.P. J. Biol. Chem. (2004) [Pubmed]
  29. Co-expression of heat shock transcription factors 1 and 2 in rat retinal ganglion cells. Kwong, J.M., Lalezary, M., Nguyen, J.K., Yang, C., Khattar, A., Piri, N., Mareninov, S., Gordon, L.K., Caprioli, J. Neurosci. Lett. (2006) [Pubmed]
WikiGenes - Universities