title: Targeting of Heat Shock Protein HSPA6 (HSP70B') to the Periphery of Nuclear Speckles is Disrupted by a Transcription Inhibitor Following Thermal Stress in Human Neuronal Cells.
abstract: Heat shock proteins (Hsps) are a set of highly conserved proteins involved in cellular repair and protective mechanisms. The intracellular localization of inducible members of the HSPA (HSP70) family can be used as an index to identify stress-sensitive sites in differentiated human neuronal cells. Following thermal stress, the little studied HSPA6 (HSP70B') was targeted to the periphery of nuclear speckles (perispeckles) that are sites of transcription factories. Triptolide, a fast-acting transcription inhibitor, knocked down levels of the large subunit of RNA polymerase II, RPB1, during the time-frame when HSPA6 associated with perispeckles. Administration of triptolide to heat shocked human neuronal SH-SY5Y cells, disrupted HSPA6 localization to perispeckles, suggesting the involvement of HSPA6 in transcriptional recovery after stress. The HSPA6 gene is present in the human genome but is not found in the genomes of the mouse and rat. Hence current animal models of neurodegenerative diseases lack a member of the HSPA family that exhibits the feature of stress-induced targeting to perispeckles.
authors.affiliation: Department of Biological Sciences, Centre for the Neurobiology of Stress, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON, M1C 1A4, Canada.
authors.forename: Larissa
authors.initials: L
authors.lastname: Becirovic
authors.affiliation: Department of Biological Sciences, Centre for the Neurobiology of Stress, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON, M1C 1A4, Canada. ibrown@utsc.utoronto.ca.
authors.forename: Ian R
authors.identifier: http://orcid.org/0000-0001-7109-6861
authors.initials: IR
authors.lastname: Brown
mesh_terms: D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000494:pharmacology; D018390:Gene Targeting / Q000379:methods*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006358:Hot Temperature / Q000009:adverse effects*; D006801:Humans; D010616:Phenanthrenes / Q000494:pharmacology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004224:Diterpenes; D004852:Epoxy Compounds; D018840:HSP70 Heat-Shock Proteins; C491129:HSPA7 protein, human; D010616:Phenanthrenes; D014157:Transcription Factors; C001899:triptolide
keywords: HSPA6 (HSP70B′); Human neuronal SH-SY5Y cells; Triptolide