Anti-Estrogen Receptor alpha Rabbit (Clone RM494)

Estrogen receptor alpha (ERalpha) is a member of the nuclear receptor superfamily of transcription factors encoded by ESR1 in humans that has a key role in reproductive function and additional roles in cancer progression and inhibition. Alternative splicing of ESR1 pre-mRNA produces one full-length 66 kDa isoform and two short-length 46 and 36 kDa isoforms, which contain truncated C-termini. ERalpha is composed of an N-terminal domain that contains AF-1, which is critical for the transactivation function of ERalpha, a DNA-binding domain that recognizes estrogen response elements (EREs) on target genes, and a C-terminal ligand-binding domain (LBD) that contains the nuclear localization signal. ERalpha is widely expressed in numerous tissues, including breast, prostate, uterus, liver, and bone, and localizes to the cytoplasm in a complex with heat shock protein 90 (Hsp90). Upon estrogen stimulation, ERalpha dissociates from Hsp90, dimerizes, and translocates to the nucleus, where it binds EREs expressed by target genes encoding proteins that activate numerous signaling pathways, including ERK/MAPK, PI3K/Akt/mTOR, and NF-kappaB, and influence a variety of cellular processes, including reproductive function, bone homeostasis, and inflammation, as well as tumor progression and metastasis. ERalpha is overexpressed in more than 50% of patients with breast cancer, but is associated with improved prognosis, whereas loss of ERalpha is a feature of triple-negative breast cancer (TNBC) and is associated with resistance to hormonal therapy. Cayman's Estrogen Receptor alpha Rabbit Monoclonal Antibody (Clone RM494) can be used for immunohistochemistry (IHC) and Western blot (WB) applications.. Cross reactivity: (+) ERalpha: . (+) Human: .. Protein function: Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE- independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa- B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements, the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full-length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1. [The UniProt Consortium]