Basal PIR expression in HeLa cells is driven by NRF2 via evolutionary conserved antioxidant response element

Area of Science:

• Molecular Biology
• Gene Regulation
• Cancer Biology

Background:

• Pirin is an iron-binding protein involved in transcriptional regulation, interacting with NF-κB pathway proteins.
• Altered pirin expression is linked to tumors and oxidative stress, suggesting a role in disease pathogenesis.

Purpose of the Study:

• To investigate the transcriptional regulation of the human PIR gene.
• To identify key regulatory elements and transcription factors controlling PIR gene expression.

Main Methods:

• Utilized luciferase reporter assays with varying PIR promoter constructs in HeLa cells.
• Employed in vivo binding assays to confirm transcription factor interaction with the PIR promoter.

Main Results:

• PIR transcription is primarily driven by a conserved antioxidant response element (ARE) located 281 bp downstream of the transcription start site.
• The transcription factor NRF2 directly binds to this ARE and regulates basal PIR expression.

Conclusions:

• NRF2-mediated regulation of the PIR gene is a key finding.
• This mechanism may allow NRF2 to influence NF-κB signaling and other pathways, impacting cellular responses to stress and disease.