Anti-ER-α36: Rabbit Estrogen Receptor alpha36 Antibody

BACKGROUND Estrogen Receptors (ERs) are multidomain transcription regulators whose activity is regulated by ligand binding. Two major ER subtypes, alpha and beta, have both overlapping and unique roles in estrogen-dependent action in vivo. ERalpha and ERbeta have different transcriptional activities in certain ligand, cell-type, and promoter contexts. When coexpressed, ERbeta exhibits an inhibitory action on ERalpha-mediated gene expression and in many instances opposes the actions of ERalpha.

A number of ERalpha and ERbeta isoforms have been described, many of which alter estrogen-mediated gene expression. ER-alpha has three splicing isoforms: full-length ER-alpha66, ER-alpha46, and ER-alpha36.

The shorter 46-kDa isoform of ER lacks exon 1 and consequently the N-terminal AF-1 region. This isoform heterodimerizes with wild-type ER-alpha66, thereby suppressing its AF-1–dependent transcriptional activity.

ER-alpha36 predominantly localizes to the plasma membrane and cytoplasm, lacks intrinsic transcriptional activity, and mainly mediates nongenomic estrogen signaling.¹ ER-alpha36 transduces both estrogen- and antiestrogen-dependent activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathway and stimulates cell growth. hER-α36 inhibits the estrogen-dependent and estrogen-independent transactivational activities of hER-α66 and hER-β.

ER-mediated gene transcription is regulated by the binding of estrogens or Selective Estrogen Receptor Modulators (SERMs), as well as post-translational events such as receptor phosphorylation, which can be induced both by the binding of estrogen and SERMs and by mitogen-activated protein kinase (MAPK) pathways. ER-alpha is phosphorylated on multiple amino acid residues. Ser104, 106, 118, and 167 are all located within the activation function (AF)1 region of ER-alpha, and their phosphorylation provides the important mechanism that regulates AF1 activity.²  ER function is also modulated by interactions with coactivators and corepressors that can either positively or negatively modulate ERalpha-mediated transcriptional   activity. Growth factor signaling (e.g. EGFR/HER2) may stimulate ER signaling via activation of both ER and the important ER coactivator AIB1/SRC-3.³

It is prevailingly considered that ER acts as a transcription factor that is mainly localized in the cell nucleus. However, accumulating evidence has demonstrated that ER also exists on the plasma membrane and participates in rapid estrogen signaling. Association of ER and Caveolin-1 also was shown to facilitate ER localization on the plasma membrane in caveolae. It was postulated that estrogen may rapidly activate different signaling pathways, including MAPK/ERK, phospholipase C, PI3K/Akt and G protein coupled receptor-activated pathways in the caveolae.⁴

RECENT PUBLICATIONS

Chaudhri, A. Hadadi, K. Lobachev, Z. Schwartz, and B. Boyan. 2014. Estrogen receptor-alpha 36 mediates the anti-apoptotic effect of estradiol in triple negative breast cancer cells via a membrane-associated mechanism. BBA 1843:2796–2806.

REFERENCES

1. Lin, S.L. et al: PLoS ONE 5:e9103, 2010
2. Yamashita, H. et al: Breast Cancer Res.7:R753-R764, 2005
3. Osborne, C.K. & Schiff, R.: Breast 12:362-7, 2003
4. Sotgia, F. et al: Cancer Res.66:10647-51, 2006

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*Optimal working dilutions must be determined by end user.