title: Basal PIR expression in HeLa cells is driven by NRF2 via evolutionary conserved antioxidant response element.
abstract: Pirin, a product of the PIR gene, is an iron-binding protein acting as a transcriptional coregulator implicated in the regulation of the NF-κB-related transcription via interaction with RelA (p65), as well as BCL3 and NF-κB1 (p50) proteins. Alterations in pirin expression were observed in various tumors and under oxidative stress conditions. The aim of the present work was to analyze the regulation of the transcription of the human PIR gene. Using constructs containing a different sized PIR promoter and the luciferase reporter genes we found that in HeLa cells PIR transcription is mostly dependent on a highly conserved antioxidant response element located 281 bp downstream of the transcription start site. We have proved that the NRF2 transcription factor binds to this element in vivo and drives the basal PIR expression. We hypothesize that regulation of the PIR expression may constitute a mechanism by which NRF2 is able to modulate the activity of NF-κB and possibly other signaling pathways.
authors.affiliation: Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195, Warsaw, Poland, k.brzoska@ichtj.waw.pl.
authors.forename: Kamil
authors.initials: K
authors.lastname: Brzóska
authors.forename: Tomasz M
authors.initials: TM
authors.lastname: Stępkowski
authors.forename: Marcin
authors.initials: M
authors.lastname: Kruszewski
mesh_terms: D000595:Amino Acid Sequence; D061745:Antioxidant Response Elements / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D049308:Dioxygenases; D005786:Gene Expression Regulation / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D016415:Sequence Alignment; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D024363:Transcription Initiation Site; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D049308:Dioxygenases; C105340:PIR protein, human