Pirin as a Modulator in Inflammation-Driven Liver Carcinogenesis

Pirin (PIR) is a 32 kDa iron-binding protein belonging to the cupin superfamily, with well-recognised roles that include functioning as a transcriptional co-regulator. 1 A single ferrous ion (Fe² + ) is housed within the N-terminal domain, where it serves as a redox-sensitive allosteric site.

2 This iron-binding region is critical for modulating PIR's conformational dynamics and subcellular localisation in response to fluctuations in the intracellular redox state. 3 Under oxidative conditions, PIR undergoes a redox-dependent transition from its reduced Fe² + (inactive) to oxidized Fe 3 + (active) form.

3 This conformational change enhances its binding affinity for multiple transcription factors, including nuclear factor I (NF-I), B-cell lymphoma 3-encoded protein and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B) subunits p50 and p65/v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA) amplifying the expression of downstream genes. 4 Through these molecular interactions, PIR acts as a key modulator within...