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Example sentences for: chaperones
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Roughly 40% (14/36) of the top characterized genes associated with this group encode protein-folding chaperones localized to different subcellular regions (including those that encode the cytosolic Hsp90 and Hsp70 factors, the mitochondrial Hsp10/Hsp60p and Ssc1p, and the ER- and mitochondrial-associated Ssa1p), and their induction following heat shock and diamide treatment is likely to be in response to widespread protein unfolding inflicted by these conditions.
ER function is critical if protein synthesis and folding is to successfully occur in eukaryotic cells [ 11 12 ] . ER stress, induced by cellular events as diverse as disrupted calcium homeostasis, elevated levels of reactive oxygen species and viral infection, leads to accumulation of dysfunctional ER chaperones and misfolded proteins [ 11 ] . Cells respond by one or both of two conserved stress response pathways.
Members of the HSP70 family have also been proposed to be involved with HSP90 chaperones regulating signal transduction pathways [ 32 ] . Unlike HSP70, HSC70 does not exhibit increased gene expression when exposed to heat stress or other agents such as sodium arsenate in the gastrula and neurula Xenopus embryo [ 33 ] . Tsang [ 34 ] suggested because of their ability to bind and transport folded and un-folded cellular proteins, HSP70 family members may function as a cross-linker to couple cellular proteins to the cytoskeletal matrix.
The first, the ER overload response, triggers the activation of the transcription factor NFkB and the subsequent upregulation of inflammatory proteins [ 13 ] . The second, the unfolded protein response (UPR) induces three divergent cellular events: (i) the activation of transcription factor ATF6 leading to the upregulation of ER chaperones such as protein disulfide isomerase, (ii) upregulation of the pro-apoptotic transcription factor GADD153 and (iii) suppression of protein synthesis via phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) by pancreatic eIF2α kinase (PEK/PERK, [ 11 12 ] ). Upregulation of the ER chaperones, GADD153 and PERK in response to a toxic insult would constitute direct evidence of an ER stress response.
The functional significance of surface expression of ER chaperones in different cell types has yet to be determined.
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