Basal PIR Expression in HeLa Cells is Driven by NRF2 Via Evolutionary Conserved Antioxidant Response Element
Overview
Affiliations
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.
Meschkewitz M, Lisabeth E, Cab-Gomez A, Leipprandt J, Neubig R bioRxiv. 2024; .
PMID: 39677728 PMC: 11642861. DOI: 10.1101/2024.12.03.626411.
Pirin Inhibits FAS-Mediated Apoptosis to Support Colorectal Cancer Survival.
Ma H, Suleman M, Zhang F, Cao T, Wen S, Sun D Adv Sci (Weinh). 2023; 11(10):e2301476.
PMID: 38148593 PMC: 10933653. DOI: 10.1002/advs.202301476.
Ahsan T, Shoily S, Ahmed T, Sajib A PLoS One. 2023; 18(11):e0289158.
PMID: 38033031 PMC: 10688961. DOI: 10.1371/journal.pone.0289158.
Lee J, Hyun D Antioxidants (Basel). 2023; 12(4).
PMID: 37107292 PMC: 10135822. DOI: 10.3390/antiox12040918.
NFIXing Cancer: The Role of NFIX in Oxidative Stress Response and Cell Fate.
Ribeiro V, Martins S, Lopes A, Thorsteinsdottir S, Zilhao R, Carlos A Int J Mol Sci. 2023; 24(5).
PMID: 36901722 PMC: 10001739. DOI: 10.3390/ijms24054293.