HSF1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| |||||||||||||||||||||||||||||||||||||||||||||||||||
Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
Aliases | HSF1, HSTF1, heat shock transcription factor 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 140580; MGI: 96238; HomoloGene: 74556; GeneCards: HSF1; OMA:HSF1 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
|
Heat shock factor 1 (HSF 1) is a protein that in humans is encoded by the HSF1 gene.[4] HSF1 is highly conserved in eukaryotes and is the primary mediator of transcriptional responses to proteotoxic stress with important roles in non-stress regulation such as development and metabolism.[5]
Structure[edit]
Human HSF1 consists of several domains which regulate its binding and activity.
DNA-Binding Domain (DBD)[edit]
This N-terminal domain of approximately 100 amino acids is the most highly conserved region in the HSF protein family and consists of a helix-turn-helix loop. The DBD of each HSF1 monomer recognizes the sequence nGAAn on target DNA. Repeated sequences of the nGAAn pentamer constitute heat shock elements (HSEs) for active HSF1 trimers to bind.[6]
Oligomerization Domain (Leucine Zipper Domains)[edit]
The two regions responsible for oligomerization between HSF1 monomers are leucine zipper (LZ) domains 1-3 and 4[7] (these regions are also commonly referred to as HR-A/B and HR-C).[6] LZ1-3 is situated just downstream of the DBD while LZ4 is located between the RD and the C-terminal TAD. Under non-stress conditions, spontaneous HSF1 activation is negatively regulated by the interaction between LZ1-3 and LZ4. When induced by stress, the LZ1-3 region breaks away from the LZ4 region and forms a trimer with other HSF1 LZ1-3 domains to form a triple coiled-coil.[7]
Regulatory Domain (RD)[edit]
The structures of the C-terminal RD and TAD of HSF1 have not been clearly resolved due to their dynamic nature.[8] However, it is known that the RD is situated between the two regions of the oligomerization domain. The RD has been shown to regulate the TAD through negative control by repressing TAD in the absence of stress, a role that is inducibly regulated through posttranslational modifications.[6][7]
Trans-Activation Domain (TAD)[edit]
This C-terminal region spans the last 150 amino acids of the HSF1 protein and contains 2 TADs (TAD1 and TAD2). TAD1, which sits at amino acids 401-420, is largely hydrophobic and is predicted to take on an alpha-helical conformation. TAD1 has been shown to directly interact with target DNA to direct HSF1's transcriptional activation. The structure of TAD2, amino acids 431-529, is not expected to be helical as it contains proline residues in addition to hydrophobic and acidic ones.[6] The function of the HSF1 TAD is still largely uncharacterized, but Hsp70 has been shown to bind with this domain, which could describe the mechanism by which Hsp70 negatively regulates HSF1.[7]
Function[edit]
The HSF1 protein regulates the heat shock response (HSR) pathway in humans by acting as the major transcription factor for heat shock proteins. The HSR plays a protective role by ensuring proper folding and distribution of proteins within cells. This pathway is induced by not only temperature stress, but also by a variety of other stressors such as hypoxic conditions and exposure to contaminants.[7] HSF1 transactivates genes for many cytoprotective proteins involved in heat shock, DNA damage repair, and metabolism. This illustrates the versatile role of HSF1 in not only the heat shock response, but also in aging and diseases.[7]
Mechanism of action[edit]
Under non-stress conditions, HSF1 exists primarily as an inactive monomer located throughout the nucleus and the cytoplasm. In its monomeric form, HSF1 activation is repressed by interaction with chaperones such as heat shock proteins Hsp70 and Hsp90, and TRiC/CCT.[7][9] In the event of proteotoxic stress such as heat shock, these chaperones are released from HSF1 to perform their protein-folding roles; simultaneously, the export of HSF1 to the cytoplasm is inhibited. These actions allow HSF1 to trimerize and accumulate in the nucleus to stimulate transcription of target genes.[6][7][10]
Clinical significance[edit]
HSF1 is a promising drug target in cancer and proteopathy.[11]
The genes activated by HSF1 under heat shock conditions have been recently shown to differ from those activated in malignant cancer cells, and this cancer-specific HSF1 panel of genes has indicated poor prognosis in breast cancer. The ability of cancer cells to use HSF1 in a unique manner gives this protein significant clinical implications for therapies and prognoses.[12]
In the case of protein-folding diseases such as Huntington's disease (HD), however, induction of the heat shock response pathway would prove beneficial. In recent years, using cells that express the poly-glutamine expansion found in HD, it has been shown that both the HSR and HSF1 levels are reduced after heat shock. This reduced ability of diseased cells to respond to stress helps to explain the toxicity associated with certain diseases.[13]
Interactions[edit]
HSF1 has been shown to interact with:
CEBPB,[14] HSF2,[15] HSPA1A,[16][17] HSPA4,[18][19] Heat shock protein 90kDa alpha (cytosolic) member A1,[20][18] NCOA6,[21] RALBP1[20] and SYMPK.[22]
See also[edit]
References[edit]
- ^ a b c ENSG00000284774 GRCh38: Ensembl release 89: ENSG00000185122, ENSG00000284774 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Rabindran SK, Giorgi G, Clos J, Wu C (August 1991). "Molecular cloning and expression of a human heat shock factor, HSF1". Proceedings of the National Academy of Sciences of the United States of America. 88 (16): 6906–10. Bibcode:1991PNAS...88.6906R. doi:10.1073/pnas.88.16.6906. PMC 52202. PMID 1871105.
- ^ Vihervaara A, Sistonen L (January 2014). "HSF1 at a glance". Journal of Cell Science. 127 (Pt 2): 261–6. doi:10.1242/jcs.132605. PMID 24421309.
- ^ a b c d e Anckar J, Sistonen L (2011-06-15). "Regulation of HSF1 function in the heat stress response: implications in aging and disease". Annual Review of Biochemistry. 80 (1): 1089–115. doi:10.1146/annurev-biochem-060809-095203. PMID 21417720.
- ^ a b c d e f g h Dayalan Naidu S, Dinkova-Kostova AT (January 2017). "Regulation of the mammalian heat shock factor 1". The FEBS Journal. 284 (11): 1606–1627. doi:10.1111/febs.13999. PMID 28052564.
- ^ Neudegger T, Verghese J, Hayer-Hartl M, Hartl FU, Bracher A (February 2016). "Structure of human heat-shock transcription factor 1 in complex with DNA". Nature Structural & Molecular Biology. 23 (2): 140–6. doi:10.1038/nsmb.3149. PMID 26727489. S2CID 684842.
- ^ "Entrez Gene: HSF1 heat shock transcription factor 1".
- ^ Shamovsky I, Nudler E (March 2008). "New insights into the mechanism of heat shock response activation". Cellular and Molecular Life Sciences. 65 (6): 855–61. doi:10.1007/s00018-008-7458-y. PMC 11131843. PMID 18239856. S2CID 9912334.
- ^ Anckar J, Sistonen L (March 2011). "Regulation of HSF1 function in the heat stress response: implications in aging and disease". Annual Review of Biochemistry. 80: 1089–115. doi:10.1146/annurev-biochem-060809-095203. PMID 21417720.
- ^ Mendillo ML, Santagata S, Koeva M, Bell GW, Hu R, Tamimi RM, Fraenkel E, Ince TA, Whitesell L, Lindquist S (August 2012). "HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers". Cell. 150 (3): 549–62. doi:10.1016/j.cell.2012.06.031. PMC 3438889. PMID 22863008.
- ^ Chafekar SM, Duennwald ML (2012-05-23). "Impaired heat shock response in cells expressing full-length polyglutamine-expanded huntingtin". PLOS ONE. 7 (5): e37929. Bibcode:2012PLoSO...737929C. doi:10.1371/journal.pone.0037929. PMC 3359295. PMID 22649566.
- ^ Xie Y, Chen C, Stevenson MA, Auron PE, Calderwood SK (April 2002). "Heat shock factor 1 represses transcription of the IL-1beta gene through physical interaction with the nuclear factor of interleukin 6". The Journal of Biological Chemistry. 277 (14): 11802–10. doi:10.1074/jbc.M109296200. PMID 11801594.
- ^ He H, Soncin F, Grammatikakis N, Li Y, Siganou A, Gong J, Brown SA, Kingston RE, Calderwood SK (September 2003). "Elevated expression of heat shock factor (HSF) 2A stimulates HSF1-induced transcription during stress". The Journal of Biological Chemistry. 278 (37): 35465–75. doi:10.1074/jbc.M304663200. PMID 12813038.
- ^ Shi Y, Mosser DD, Morimoto RI (March 1998). "Molecular chaperones as HSF1-specific transcriptional repressors". Genes & Development. 12 (5): 654–66. doi:10.1101/gad.12.5.654. PMC 316571. PMID 9499401.
- ^ Zhou X, Tron VA, Li G, Trotter MJ (August 1998). "Heat shock transcription factor-1 regulates heat shock protein-72 expression in human keratinocytes exposed to ultraviolet B light". The Journal of Investigative Dermatology. 111 (2): 194–8. doi:10.1046/j.1523-1747.1998.00266.x. PMID 9699716.
- ^ a b Nair SC, Toran EJ, Rimerman RA, Hjermstad S, Smithgall TE, Smith DF (December 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 (inactive 2024-04-02). PMC 376461. PMID 9222609.
{{cite journal}}
: CS1 maint: DOI inactive as of April 2024 (link) - ^ Abravaya K, Myers MP, Murphy SP, Morimoto RI (July 1992). "The human heat shock protein hsp70 interacts with HSF, the transcription factor that regulates heat shock gene expression". Genes & Development. 6 (7): 1153–64. doi:10.1101/gad.6.7.1153. PMID 1628823.
- ^ a b Hu Y, Mivechi NF (May 2003). "HSF-1 interacts with Ral-binding protein 1 in a stress-responsive, multiprotein complex with HSP90 in vivo". The Journal of Biological Chemistry. 278 (19): 17299–306. doi:10.1074/jbc.M300788200. PMID 12621024.
- ^ Hong S, Kim SH, Heo MA, Choi YH, Park MJ, Yoo MA, Kim HD, Kang HS, Cheong J (February 2004). "Coactivator ASC-2 mediates heat shock factor 1-mediated transactivation dependent on heat shock". FEBS Letters. 559 (1–3): 165–70. doi:10.1016/S0014-5793(04)00028-6. PMID 14960326. S2CID 22383479.
- ^ Xing H, Mayhew CN, Cullen KE, Park-Sarge OK, Sarge KD (March 2004). "HSF1 modulation of Hsp70 mRNA polyadenylation via interaction with symplekin". The Journal of Biological Chemistry. 279 (11): 10551–5. doi:10.1074/jbc.M311719200. PMID 14707147.
Further reading[edit]
- Voellmy R (1996). "Sensing stress and responding to stress". Stress-Inducible Cellular Responses. Vol. 77. pp. 121–37. doi:10.1007/978-3-0348-9088-5_9. ISBN 978-3-0348-9901-7. PMID 8856972.
{{cite book}}
:|journal=
ignored (help) - Abravaya K, Myers MP, Murphy SP, Morimoto RI (July 1992). "The human heat shock protein hsp70 interacts with HSF, the transcription factor that regulates heat shock gene expression". Genes & Development. 6 (7): 1153–64. doi:10.1101/gad.6.7.1153. PMID 1628823.
- Schuetz TJ, Gallo GJ, Sheldon L, Tempst P, Kingston RE (August 1991). "Isolation of a cDNA for HSF2: evidence for two heat shock factor genes in humans". Proceedings of the National Academy of Sciences of the United States of America. 88 (16): 6911–5. Bibcode:1991PNAS...88.6911S. doi:10.1073/pnas.88.16.6911. PMC 52203. PMID 1871106.
- Nunes SL, Calderwood SK (August 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". Biochemical and Biophysical Research Communications. 213 (1): 1–6. doi:10.1006/bbrc.1995.2090. PMID 7639722.
- Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Chu B, Soncin F, Price BD, Stevenson MA, Calderwood SK (November 1996). "Sequential phosphorylation by mitogen-activated protein kinase and glycogen synthase kinase 3 represses transcriptional activation by heat shock factor-1". The Journal of Biological Chemistry. 271 (48): 30847–57. doi:10.1074/jbc.271.48.30847. PMID 8940068.
- Fukunaga R, Hunter T (April 1997). "MNK1, a new MAP kinase-activated protein kinase, isolated by a novel expression screening method for identifying protein kinase substrates". The EMBO Journal. 16 (8): 1921–33. doi:10.1093/emboj/16.8.1921. PMC 1169795. PMID 9155018.
- Nair SC, Toran EJ, Rimerman RA, Hjermstad S, Smithgall TE, Smith DF (December 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 (inactive 2024-04-02). PMC 376461. PMID 9222609.
{{cite journal}}
: CS1 maint: DOI inactive as of April 2024 (link) - Huang J, Nueda A, Yoo S, Dynan WS (October 1997). "Heat shock transcription factor 1 binds selectively in vitro to Ku protein and the catalytic subunit of the DNA-dependent protein kinase". The Journal of Biological Chemistry. 272 (41): 26009–16. doi:10.1074/jbc.272.41.26009. PMID 9325337.
- Cotto J, Fox S, Morimoto R (December 1997). "HSF1 granules: a novel stress-induced nuclear compartment of human cells". Journal of Cell Science. 110 ( Pt 23) (23): 2925–34. doi:10.1242/jcs.110.23.2925. PMID 9359875.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Shi Y, Mosser DD, Morimoto RI (March 1998). "Molecular chaperones as HSF1-specific transcriptional repressors". Genes & Development. 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 (July 1998). "Negative regulation of the heat shock transcriptional response by HSBP1". Genes & Development. 12 (13): 1962–74. doi:10.1101/gad.12.13.1962. PMC 316975. PMID 9649501.
- Zhou X, Tron VA, Li G, Trotter MJ (August 1998). "Heat shock transcription factor-1 regulates heat shock protein-72 expression in human keratinocytes exposed to ultraviolet B light". The Journal of Investigative Dermatology. 111 (2): 194–8. doi:10.1046/j.1523-1747.1998.00266.x. PMID 9699716.
- Zou J, Guo Y, Guettouche T, Smith DF, Voellmy R (August 1998). "Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1". Cell. 94 (4): 471–80. doi:10.1016/S0092-8674(00)81588-3. PMID 9727490. S2CID 9234420.
- Stephanou A, Isenberg DA, Nakajima K, Latchman DS (January 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". The Journal of Biological Chemistry. 274 (3): 1723–8. doi:10.1074/jbc.274.3.1723. PMID 9880553.
- Dai R, Frejtag W, He B, Zhang Y, Mivechi NF (June 2000). "c-Jun NH2-terminal kinase targeting and phosphorylation of heat shock factor-1 suppress its transcriptional activity". The Journal of Biological Chemistry. 275 (24): 18210–8. doi:10.1074/jbc.M000958200. PMID 10747973.
- Choi Y, Asada S, Uesugi M (May 2000). "Divergent hTAFII31-binding motifs hidden in activation domains". The Journal of Biological Chemistry. 275 (21): 15912–6. doi:10.1074/jbc.275.21.15912. PMID 10821850.
External links[edit]
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
Well, that’s interesting to know that Psilotum nudum are known as whisk ferns. Psilotum nudum is the commoner species of the two. While the P. flaccidum is a rare species and is found in the tropical islands. Both the species are usually epiphytic in habit and grow upon tree ferns. These species may also be terrestrial and grow in humus or in the crevices of the rocks.
View the detailed Guide of Psilotum nudum: Detailed Study Of Psilotum Nudum (Whisk Fern), Classification, Anatomy, Reproduction