ER alpha/ESR1 Protein, Human (His)

ER alpha/ESR1 Protein, a nuclear hormone receptor, plays a pivotal role in the regulation of eukaryotic gene expression, influencing cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves direct homodimer binding to palindromic estrogen response element (ERE) sequences or association with DNA-binding transcription factors like AP-1/c-Jun, c-Fos, ATF-2, Sp1, and Sp3, facilitating ERE-independent signaling. Upon ligand binding, ER alpha undergoes a conformational change, enabling subsequent association with multiprotein coactivator complexes through LXXLL motifs. Mutual transrepression occurs between ER alpha and NF-kappa-B in a cell-type specific manner, leading to decreased NF-kappa-B DNA-binding activity and inhibition of NF-kappa-B-mediated transcription. ER alpha is recruited to NF-kappa-B response elements, displacing coregulators and mediating transcriptional activation synergistically with NF-kappa-B. Moreover, ER alpha participates in membrane-initiated estrogen signaling through various kinase cascades, and is essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Additionally, ER alpha is involved in the activation of NOS3 and endothelial nitric oxide production. Isoforms lacking specific functional domains are believed to modulate transcriptional activity through competitive ligand or DNA binding, as well as heterodimerization with the full-length receptor. Furthermore, ER alpha binds to ERE and inhibits isoform 1.