HSF1

Heat shock transcription factor 1
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2LDU​
Identifiers
Symbols	HSF1 ; HSTF1
External IDs	OMIM: 140580 MGI: 96238 HomoloGene: 74556 ChEMBL: 5869 GeneCards: HSF1 Gene
Gene ontology Molecular function • RNA polymerase II core promoter proximal region sequence-specific DNA binding • transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding • RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding • chromatin binding • transcription factor activity, sequence-specific DNA binding • protein binding Cellular component • nucleoplasm • cytoplasm • cytosol • protein complex • pronucleus Biological process • negative regulation of transcription from RNA polymerase II promoter • embryonic placenta development • protein phosphorylation • defense response • female meiotic division • spermatogenesis • negative regulation of cell proliferation • mRNA transcription • response to lipopolysaccharide • negative regulation of tumor necrosis factor production • cellular response to heat • positive regulation of multicellular organism growth • positive regulation of transcription from RNA polymerase II promoter • embryonic process involved in female pregnancy • regulation of cellular response to heat Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3297	15499
Ensembl	ENSG00000185122	ENSMUSG00000022556
UniProt	Q00613	P38532
RefSeq (mRNA)	NM_005526	NM_008296
RefSeq (protein)	NP_005517	NP_032322
Location (UCSC)	Chr 8: 144.29 – 144.31 Mb	Chr 15: 76.48 – 76.5 Mb
PubMed search

Heat shock factor protein 1 is a protein that in humans is encoded by the HSF1 gene.^[1]

Function

The product of this gene is a heat-shock transcription factor. Transcription of heat-shock genes is rapidly induced after temperature stress. Hsp90, by itself and/or associated with multichaperone complexes, is a major repressor of this gene.^[2]

Mechanism of action

HSF1 exists as an inactive monomer in a complex with Hsp40/Hsp70 and Hsp90. Upon stress, such as elevated temperature, HSF1 is released from the chaperone complex and trimerizes. HSF1 is then transported into the nucleus where it is hyperphosphorylated and binds to DNA containing heat shock elements (NGAAN). HSF1's target genes include major inducible heat shock proteins such as Hsp72, and noncoding RNA within Satellite III repeat regions. Its attenuation phase is initiated as a negative feedback loop with its gene product Hsp70 binding to its transactivation domain.^[3]

Relevance

HSF1 is a promising drug target in cancer and proteopathy.^[4]

Interactions

HSF1 has been shown to interact with:

• CEBPB,^[5]
• HSF2,^[6]
• HSPA1A,^[7][8]
• HSPA4,^[9][10]
• Heat shock protein 90kDa alpha (cytosolic), member A1^[11][9]
• NCOA6,^[12]
• RALBP1,^[11] and
• SYMPK.^[13]

See also

• Heat shock factor

References

1. Rabindran SK, Giorgi G, Clos J, Wu C (Sep 1991). "Molecular cloning and expression of a human heat shock factor, HSF1". Proc Natl Acad Sci U S A 88 (16): 6906–6910. doi:10.1073/pnas.88.16.6906. PMC 52202. PMID 1871105.
2. "Entrez Gene: HSF1 heat shock transcription factor 1".
3. Shamovsky I, Nudler E (March 2008). "New insights into the mechanism of heat shock response activation". Cell. Mol. Life Sci. 65 (6): 855–861. doi:10.1007/s00018-008-7458-y. PMID 18239856.
4. Anckar J, Sistonen L (March 2011). "Regulation of HSF1 function in the heat stress response: implications in aging and disease". Annu Rev Biochem 80: 1089–1115. doi:10.1146/annurev-biochem-060809-095203. PMID 21417720.
5. Xie Y, Chen C, Stevenson MA, Auron PE, Calderwood SK (Apr 2002). "Heat shock factor 1 represses transcription of the IL-1beta gene through physical interaction with the nuclear factor of interleukin 6". J. Biol. Chem. 277 (14): 11802–10. doi:10.1074/jbc.M109296200. PMID 11801594.
6. He H, Soncin F, Grammatikakis N, Li Y, Siganou A, Gong J, Brown SA, Kingston RE, Calderwood SK (Sep 2003). "Elevated expression of heat shock factor (HSF) 2A stimulates HSF1-induced transcription during stress". J. Biol. Chem. 278 (37): 35465–75. doi:10.1074/jbc.M304663200. PMID 12813038.
7. Shi Y, Mosser DD, Morimoto RI (Mar 1998). "Molecular chaperones as HSF1-specific transcriptional repressors". Genes Dev. 12 (5): 654–66. doi:10.1101/gad.12.5.654. PMC 316571. PMID 9499401.
8. Zhou X, Tron VA, Li G, Trotter MJ (Aug 1998). "Heat shock transcription factor-1 regulates heat shock protein-72 expression in human keratinocytes exposed to ultraviolet B light". J. Invest. Dermatol. 111 (2): 194–8. doi:10.1046/j.1523-1747.1998.00266.x. PMID 9699716.
9. Nair SC, Toran EJ, Rimerman RA, Hjermstad S, Smithgall TE, Smith DF (Dec 1996). "A pathway of multi-chaperone interactions common to diverse regulatory proteins: estrogen receptor, Fes tyrosine kinase, heat shock transcription factor Hsf1, and the aryl hydrocarbon receptor". Cell Stress Chaperones 1 (4): 237–50. doi:10.1379/1466-1268(1996)001<0237:apomci>2.3.co;2. PMC 376461. PMID 9222609.
10. Abravaya K, Myers MP, Murphy SP, Morimoto RI (Jul 1992). "The human heat shock protein hsp70 interacts with HSF, the transcription factor that regulates heat shock gene expression". Genes Dev. 6 (7): 1153–64. doi:10.1101/gad.6.7.1153. PMID 1628823.
11. Hu Y, Mivechi NF (May 2003). "HSF-1 interacts with Ral-binding protein 1 in a stress-responsive, multiprotein complex with HSP90 in vivo". J. Biol. Chem. 278 (19): 17299–306. doi:10.1074/jbc.M300788200. PMID 12621024.
12. Hong S, Kim SH, Heo MA, Choi YH, Park MJ, Yoo MA, Kim HD, Kang HS, Cheong J (Feb 2004). "Coactivator ASC-2 mediates heat shock factor 1-mediated transactivation dependent on heat shock". FEBS Lett. 559 (1-3): 165–70. doi:10.1016/S0014-5793(04)00028-6. PMID 14960326.
13. Xing H, Mayhew CN, Cullen KE, Park-Sarge OK, Sarge KD (Mar 2004). "HSF1 modulation of Hsp70 mRNA polyadenylation via interaction with symplekin". J. Biol. Chem. 279 (11): 10551–5. doi:10.1074/jbc.M311719200. PMID 14707147.

Further reading

• Voellmy R (1996). "Sensing stress and responding to stress". EXS 77: 121–37. doi:10.1007/978-3-0348-9088-5_9. PMID 8856972.
• Abravaya K, Myers MP, Murphy SP, Morimoto RI (1992). "The human heat shock protein hsp70 interacts with HSF, the transcription factor that regulates heat shock gene expression". Genes Dev. 6 (7): 1153–1164. doi:10.1101/gad.6.7.1153. PMID 1628823.
• Schuetz TJ, Gallo GJ, Sheldon L, Tempst P, Kingston RE (1991). "Isolation of a cDNA for HSF2: evidence for two heat shock factor genes in humans". Proc. Natl. Acad. Sci. U.S.A. 88 (16): 6911–6915. doi:10.1073/pnas.88.16.6911. PMC 52203. PMID 1871106.
• Nunes SL, Calderwood SK (1995). "Heat shock factor-1 and the heat shock cognate 70 protein associate in high molecular weight complexes in the cytoplasm of NIH-3T3 cells". Biochem. Biophys. Res. Commun. 213 (1): 1–6. doi:10.1006/bbrc.1995.2090. PMID 7639722.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Chu B, Soncin F, Price BD, Stevenson MA, Calderwood SK (1997). "Sequential phosphorylation by mitogen-activated protein kinase and glycogen synthase kinase 3 represses transcriptional activation by heat shock factor-1". J. Biol. Chem. 271 (48): 30847–30857. doi:10.1074/jbc.271.48.30847. PMID 8940068.
• Fukunaga R, Hunter T (1997). "MNK1, a new MAP kinase-activated protein kinase, isolated by a novel expression screening method for identifying protein kinase substrates". EMBO J. 16 (8): 1921–1933. doi:10.1093/emboj/16.8.1921. PMC 1169795. PMID 9155018.
• Nair SC, Toran EJ, Rimerman RA, Hjermstad S, Smithgall TE, Smith DF (1997). "A pathway of multi-chaperone interactions common to diverse regulatory proteins: estrogen receptor, Fes tyrosine kinase, heat shock transcription factor Hsf1, and the aryl hydrocarbon receptor". Cell Stress Chaperones 1 (4): 237–50. doi:10.1379/1466-1268(1996)001<0237:APOMCI>2.3.CO;2. PMC 376461. PMID 9222609.
• Huang J, Nueda A, Yoo S, Dynan WS (1997). "Heat shock transcription factor 1 binds selectively in vitro to Ku protein and the catalytic subunit of the DNA-dependent protein kinase". J. Biol. Chem. 272 (41): 26009–26016. doi:10.1074/jbc.272.41.26009. PMID 9325337.
• Cotto J, Fox S, Morimoto R (1998). "HSF1 granules: a novel stress-induced nuclear compartment of human cells". J. Cell. Sci. 110 (23): 2925–34. PMID 9359875.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Shi Y, Mosser DD, Morimoto RI (1998). "Molecular chaperones as HSF1-specific transcriptional repressors". Genes Dev. 12 (5): 654–66. doi:10.1101/gad.12.5.654. PMC 316571. PMID 9499401.
• Satyal SH, Chen D, Fox SG, Kramer JM, Morimoto RI (1998). "Negative regulation of the heat shock transcriptional response by HSBP1". Genes Dev. 12 (13): 1962–1974. doi:10.1101/gad.12.13.1962. PMC 316975. PMID 9649501.
• Zhou X, Tron VA, Li G, Trotter MJ (1998). "Heat shock transcription factor-1 regulates heat shock protein-72 expression in human keratinocytes exposed to ultraviolet B light". J. Invest. Dermatol. 111 (2): 194–198. doi:10.1046/j.1523-1747.1998.00266.x. PMID 9699716.
• Zou J, Guo Y, Guettouche T, Smith DF, Voellmy R (1998). "Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1". Cell 94 (4): 471–480. doi:10.1016/S0092-8674(00)81588-3. PMID 9727490.
• Stephanou A, Isenberg DA, Nakajima K, Latchman DS (1999). "Signal transducer and activator of transcription-1 and heat shock factor-1 interact and activate the transcription of the Hsp-70 and Hsp-90beta gene promoters". J. Biol. Chem. 274 (3): 1723–1728. doi:10.1074/jbc.274.3.1723. PMID 9880553.
• Dai R, Frejtag W, He B, Zhang Y, Mivechi NF (2000). "c-Jun NH2-terminal kinase targeting and phosphorylation of heat shock factor-1 suppress its transcriptional activity". J. Biol. Chem. 275 (24): 18210–18218. doi:10.1074/jbc.M000958200. PMID 10747973.
• Choi Y, Asada S, Uesugi M (2000). "Divergent hTAFII31-binding motifs hidden in activation domains". J. Biol. Chem. 275 (21): 15912–15916. doi:10.1074/jbc.275.21.15912. PMID 10821850.

External links

• HES1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook HSF1

This article incorporates text from the United States National Library of Medicine, which is in the public domain.