Nuclear factor kappa-B p50–annexin A2 protein–protein interface (NF-κB p50–ANXA2 PPI)

The NF-κB p50–annexin A2 protein–protein interface is a critical regulatory node where the phospholipid-binding protein Annexin A2 (ANXA2) acts as a molecular chaperone for the p50 subunit of the NF-κB transcription factor (Jung et al., 2015, Cell Death Dis). By binding to p50, ANXA2 facilitates its translocation from the cytosol to the nucleus, thereby significantly enhancing NF-κB-mediated gene expression (Tang et al., 2022, ResearchGate). This interaction is frequently hijacked in aggressive malignancies, such as triple-negative breast cancer and pancreatic cancer, to drive tumor growth, epithelial-mesenchymal transition (EMT), and resistance to chemotherapeutic agents like gemcitabine (Wang et al., 2020, Nutrients). Beyond oncology, the interface plays a role in inflammatory pathologies, including severe acute pancreatitis and cerebral ischemia, by promoting the release of pro-inflammatory cytokines (Jung et al., 2015). Targeting this specific protein-protein interaction offers a more selective therapeutic strategy compared to broad NF-κB inhibitors, potentially reducing systemic toxicity. Several natural compounds, most notably specific ginsenosides like Compound K and Rh2, have demonstrated the ability to disrupt this interface in preclinical studies, leading to increased apoptosis and reduced metastatic potential in cancer cells (ResearchGate, 2025).

Other names

p50-ANXA2 interactionNF-kappaB p50-Annexin A2 complexANXA2-p50 interfaceAnnexin A2-NF-κB p50 protein-protein interaction

Disruption of the protein-protein interaction between Annexin A2 and the p50 subunit of NF-κB, which prevents the nuclear translocation of the NF-κB complex and inhibits the transcription of pro-survival, pro-inflammatory, and pro-metastatic genes.