Estrogen receptor alpha–Progesterone receptor B protein–protein interface (ERα–PR-B PPI) (ERα–PR-B PPI)

The Estrogen receptor alpha–Progesterone receptor B (ERα–PR-B) protein–protein interface is a critical regulatory site involved in the crosstalk between two major steroid hormone receptors in breast and reproductive tissues. ERα and PR-B are ligand-activated transcription factors that, upon binding their respective hormones, can physically associate to form a heteromeric complex (Mohammed et al., 2015, Nature). In breast cancer cells, PR-B physically interacts with ERα to modulate its genomic distribution and transcriptional activity, often acting as a molecular "brake" or "reprogrammer" of ERα-driven proliferative signaling (Singhal et al., 2016, Cell Reports). This interaction is significant because the presence of PR-B can alter the response of ERα to estrogen and anti-estrogenic therapies, such as tamoxifen. Therapeutic strategies targeting this specific interface aim to disrupt the synergistic or antagonistic crosstalk between these receptors to overcome endocrine resistance. By specifically inhibiting the PPI rather than the individual receptors, researchers hope to achieve more precise control over oncogenic signaling pathways while minimizing systemic side effects associated with total hormone blockade. Current research focuses on developing small molecules or peptidomimetics that can specifically wedge into this interface to restore hormonal sensitivity in treatment-resistant tumors.

Other names

ERα/PR-B complexESR1-PGR interfaceEstrogen receptor-Progesterone receptor crosstalk siteER-PR PPI

Disruption or modulation of the physical interaction between ERα and PR-B to prevent the reprogramming of ERα genomic binding and subsequent oncogenic gene expression.