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{{Short description|Family of proteins}}
'''Heat shock proteins''' ('''
Heat
==Discovery==
It is known that rapid heat hardening can be elicited by a brief exposure of cells to sub-lethal high temperature, which in turn provides protection from subsequent and more severe temperature. In 1962, Italian geneticist [[Ferruccio Ritossa]] reported that heat and the metabolic uncoupler [[2,4-Dinitrophenol|2,4-dinitrophenol]] induced a characteristic pattern of "[[chromosome puff|puffing]]" in the [[chromosome]]s of [[Drosophila]].<ref name="Ritossa_1962" /><ref name="Ritossa_1996">{{cite journal | vauthors = Ritossa F | title = Discovery of the heat shock response | journal = Cell Stress & Chaperones | volume = 1 | issue = 2 | pages = 97–98 | date = June 1996 | doi = 10.1379/1466-1268(1996)001<0097:dothsr>2.3.co;2 | doi-broken-date = 2024-04-26 | pmid = 9222594 | pmc = 248460 }}</ref> This discovery eventually led to the identification of the heat-shock proteins (HSP) or stress proteins whose expression this puffing represented. Increased synthesis of selected proteins in Drosophila cells following stresses such as heat shock was first reported in 1974.<ref name="MJS">{{cite journal | vauthors = Schlesinger MJ | title = Heat shock proteins | journal = The Journal of Biological Chemistry | volume = 265 | issue = 21 | pages = 12111–12114 | date = July 1990 | pmid = 2197269 | doi = 10.1016/S0021-9258(19)38314-0 | doi-access = free }}</ref> In 1974, Tissieres, Mitchell and Tracy<ref name="Tissières_1974">{{cite journal | vauthors = Tissières A, Mitchell HK, Tracy UM | title = Protein synthesis in salivary glands of Drosophila melanogaster: relation to chromosome puffs | journal = Journal of Molecular Biology | volume = 84 | issue = 3 | pages = 389–398 | date = April 1974 | pmid = 4219221 | doi = 10.1016/0022-2836(74)90447-1 }}</ref> discovered that heat-shock induces the production of a small number of proteins and inhibits the production of most others. This initial biochemical finding gave rise to a large number of studies on the induction of heat shock and its biological role. Heat shock proteins often function as [[chaperone (protein)|chaperones]] in the refolding of proteins damaged by heat stress. Heat shock proteins have been found in all species examined, from [[bacteria]] to humans, suggesting that they evolved very early and have an important function.
== Function ==
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This handing over with peptides is important, because HSPs can shield hydrophobic residues in peptides which would be otherwise problematic in aquatic cytosol. Also simple diffusion of peptides would be too ineffective.<ref name="Binder_2014" />
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In MHCII presentation, HSPs are involved in [[Receptor-mediated endocytosis|clathrin-dependent endocytosis]].<ref name="Deffit_2015" /> Also when HSPs are extracellular, they can guide their associated peptides into MHCII pathway, although it is not known how they are distinguished from the cross-presented ones (see below).<ref name="Murshid_2012" />
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==Clinical significance==
=== HSF
[[HSF1|Heat shock factor 1]] (
=== Diabetes mellitus ===
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===Anticancer therapeutics===
Intracellular heat shock proteins are highly expressed in cancerous cells and are essential to the survival of these cell types due to presence of mutated and over-expressed oncogenes.<ref name="Tukaj_2016" /> Many HSPs can also promote invasiveness and metastasis formation in tumours, block apoptosis, or promote resistance to anti-cancer drugs.<ref>{{cite journal | vauthors = Wu J, Liu T, Rios Z, Mei Q, Lin X, Cao S | title = Heat Shock Proteins and Cancer | journal = Trends in Pharmacological Sciences | volume = 38 | issue = 3 | pages = 226–256 | date = March 2017 | pmid = 28012700 | doi = 10.1016/j.tips.2016.11.009 }}</ref><ref name="Graner_2016" /> Hence [[small molecule]] [[HSP inhibitor|inhibitors of HSPs]], especially [[Hsp90]] show promise as anticancer agents.<ref name="Didelot_2007">{{cite journal | vauthors = Didelot C, Lanneau D, Brunet M, Joly AL, De Thonel A, Chiosis G, Garrido C | title = Anti-cancer therapeutic approaches based on intracellular and extracellular heat shock proteins | journal = Current Medicinal Chemistry | volume = 14 | issue = 27 | pages = 2839–2847 | year = 2007 | pmid = 18045130 | doi = 10.2174/092986707782360079 }}</ref> The potent Hsp90 inhibitor [[17-N-Allylamino-17-demethoxygeldanamycin|17-AAG]] was in [[clinical trial]]s for the treatment of several types of cancer, but for various reasons unrelated to efficacy did not go on to Phase 3.<ref name="Solit_2006">{{cite journal | vauthors = Solit DB, Rosen N | title = Hsp90: a novel target for cancer therapy | journal = Current Topics in Medicinal Chemistry | volume = 6 | issue = 11 | pages = 1205–1214 | year = 2006 | pmid = 16842157 | doi = 10.2174/156802606777812068 }}</ref><ref>{{cite journal|last1=The Myeloma Beacon Staff|title=Bristol-Myers Squibb Halts Development of Tanespimycin|journal=The Myeloma Beacon|date=22 July 2010
=== Autoimmunity treatment ===
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