title: Regulation of survival gene hsp70.
abstract: Rapid expression of the survival gene, inducible heat shock protein 70 (hsp70), is critical for mounting cytoprotection against severe cellular stress, like elevated temperature. Hsp70 protein chaperones the refolding of heat-denatured peptides to minimize proteolytic degradation as a part of an eukaryotically conserved phenomenon referred to as the heat shock response. The physiologic stress associated with exercise, which can include elevated temperature, mechanical damage, hypoxia, lowered pH, and reactive oxygen species generation, may promote protein unfolding, leading to hsp70 gene expression in skeletal myofibers. Although the pre-transcriptional activation of hsp70 gene expression has been thoroughly reviewed, discussion of downstream hsp70 gene regulation is less extensive. The purpose of this brief review was to examine all levels of hsp70 gene regulation in response to heat stress and exercise with a special focus on skeletal myofibers where data are available. In general, while heat stress represses bulk gene expression, hsp70 mRNA expression is enhanced. Post-transcriptionally, intronless hsp70 mRNA circumvents a host of decay pathways, as well as heat stress-repressed pre-mRNA splicing and nuclear export. Pre-translationally, hsp70 mRNA is excluded from stress granules and preferentially translated during heat stress-repressed global cap-dependent translation. Post-translationally, nascent Hsp70 protein is thermodynamically stable at elevated temperatures, allowing for the commencement of chaperoning activity early after synthesis to attenuate the heat shock response and protect against subsequent injury. This review demonstrates that hsp70 mRNA expression is closely coupled with functional protein translation.
authors.affiliation: School of Kinesiology, Faculty of Health Sciences, The University of Western Ontario, London, ON, Canada.
authors.forename: Jordan Thomas
authors.initials: JT
authors.lastname: Silver
authors.forename: Earl G
authors.initials: EG
authors.lastname: Noble
mesh_terms: D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger