Proteins interacting with the mammalian estrogen receptor: proposal for an integrated model for estrogen receptor mediated regulation of transcription

Abstract

Two forms of estrogen receptor (ER) that exist in the mammalian uterus have been examined in this review. (1) ERalpha, or the classical estrogen receptor that is considered to influence the transcriptional process; (2) the non-activated estrogen receptor (naER), an alternative form of ER with no DNA binding function, localized in the plasma membrane. An integrated model is being proposed to highlight the functional roles of both receptors in transcriptional regulation. The proteins with which ER interacts during various stages of its existence are being examined. These stages include: (1) transport from the cytoplasm to the nucleus; (2) interaction with the nuclear transcription machinery; (3) involvement in post-transcriptional control mechanisms; and (4) degradation through ubiquitination. The proteins with which naER interacts during its plasma membrane-to-nucleus movement have also been identified; the results have not yet been published. Within the nucleus it dimerizes with a DNA-binding protein, the estrogen receptor activation factor (E-RAF). It is being proposed that the purpose behind the dimerization between naER and E-RAF is to transport E-RAF to the transcription initiation site as the naER in the heterodimer is a RNA-polymerase binding protein. Deglycosylated naER fails to dimerize with the E-RAF. Deglycosylation of the naER therefore dissociates the heterodimer and this transformed naER is now identified as nuclear estrogen receptor II (nER II). The dissociated E-RAF is free either to destabilize (E-RAF II) or stabilize (E-RAF I) the DNA while the naER remains bound to the RNA polymerase II. nER II phosphorylates certain subunits in RNA polymerase; the functional significance of this phosphorylation remains to be known.

Immunocytochemical study of estrogen receptor activation factor (E-RAF) and the proteins that interact with nuclear estrogen receptor II (nER II) in epithelial endometrial cells, in the presence and in the absence of estradiol

“…Most of the sites of non-nucleolar transcription are located at these sites, especially at the periphery of compact or semi-condensed chromatin (Fakan and Bernhard, 1971;Bachellerie et al, 1975;Cmarko et al, 1999;Puvion and Puvion-Dutilleul, 1996;Fakan, 2004). The association of R-RAF with structures related to the process of transcription supports the proposition that the naER-E-RAF heterodimer binds to RNA-polymerase II at the site of transcription initiation (Govind and Thampan, 2001). The scattered immunocytochemical signal of E-RAF in the nucle-…”

Inhibition of Smooth Muscle Proliferation by Urea-Based Alkanoic Acids via Peroxisome Proliferator-Activated Receptor α–Dependent Repression of Cyclin D1

“…Estrogen receptor regulates nitric oxide release by physically interacting with the regulatory subunit of the lipid kinase phosphatidylinositol 3-kinase 32 and mediates estrogen-dependent transport of ribonucleoprotein from the nucleus to the cytoplasm. 33 It is therefore plausible that CUUA and AUDA exert their effects on cyclin D1 via nontranscriptional mechanisms.…”

“…Estrogen receptor regulates nitric oxide release by physically interacting with the regulatory subunit of the lipid kinase phosphatidylinositol 3-kinase 32 and mediates estrogen-dependent transport of ribonucleoprotein from the nucleus to the cytoplasm. 33 It is therefore plausible that CUUA and AUDA exert their effects on cyclin D1 via nontranscriptional mechanisms.An alternative explanation would suggest that CUUA and AUDA inhibit SMC proliferation independent of PPAR␣; however, by reducing its expression, the role of PPAR␣ was evident. In the absence of normal levels of PPAR␣, repression of cyclin D1 by alkanoic acids was greatly reduced.…”

Menin, a product of the MENI gene, binds to estrogen receptor to enhance its activity in breast cancer cells: possibility of a novel predictive factor for tamoxifen resistance

“…ERa is a ligand-activated nuclear receptor that regulates the transcription of estrogen-responsive genes in diverse target cells. ERa and its ligand 17-estradiol not only play a critical role in normal breast development but also have long been linked to mammary carcinogenesis, breast cancer progression, and outcomes of breast cancer patients [2]. Given the fact that 17-estradiol stimulates the growth of ER-positive breast tumors via functional ERs, endocrine therapy such as the use of antiestrogens or ovarian ablation has been established as an important part of breast cancer management [3].…”