title: AIRAP, a new human heat shock gene regulated by heat shock factor 1.
abstract: Heat shock factor-1 (HSF1) is the central regulator of heat-induced transcriptional responses leading to rapid expression of molecular chaperones that protect mammalian cells against proteotoxic stress. The main targets for HSF1 are specific promoter elements (HSE) located upstream of heat shock genes encoding a variety of heat shock proteins, including HSP70, HSP90, HSP27, and other proteins of the network. Herein we report that the zinc finger AN1-type domain-2a gene, also known as AIRAP, behaves as a canonical heat shock gene, whose expression is temperature-dependent and strictly controlled by HSF1. Transcription is triggered at temperatures above 40 degrees C in different types of human cancer and primary cells, including peripheral blood monocytes. As shown by ChIP analysis, HSF1 is recruited to the AIRAP promoter rapidly after heat treatment, with a kinetics that parallels HSP70 promoter HSF1-recruitment. In transfection experiments HSF1-silencing abolished heat-induced AIRAP promoter-driven transcription, which could be rescued by exogenous Flag-HSF1 expression. The HSF1 binding HSE sequence in the AIRAP promoter critical for heat-induced transcription was identified. Because its expression is induced at febrile temperatures in human cells, AIRAP may represent a new potential component of the protective response during fever in humans.
authors.affiliation: Institute of Neurobiology and Molecular Medicine, CNR, 00133 Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rossi
authors.forename: Edoardo
authors.initials: E
authors.lastname: Trotta
authors.forename: Rossella
authors.initials: R
authors.lastname: Brandi
authors.forename: Ivan
authors.initials: I
authors.lastname: Arisi
authors.forename: Marta
authors.initials: M
authors.lastname: Coccia
authors.forename: M Gabriella
authors.initials: MG
authors.lastname: Santoro
mesh_terms: D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D018869:Heat-Shock Response / Q000502:physiology*; D006358:Hot Temperature; D006801:Humans; D009000:Monocytes / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D020218:Response Elements / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C549572:ZFAND2A protein, human