Proteins interacting with the mammalian estrogen receptor: proposal for an integrated model for estrogen receptor mediated regulation of transcription.
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.
Govind
A P
AP
Rajiv Gandhi Centre for Biotechnology, Jagathy, Thiruvananthapuram 695 014, Kerala, India.
Thampan
R V
RV
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D019281:Dimerization; D005786:Gene Expression Regulation; D006031:Glycosylation; D006801:Humans; D008954:Models, Biological; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011960:Receptors, Estrogen / Q000378:metabolism*; D014158:Transcription, Genetic
D011960:Receptors, Estrogen