Insight into the mechanisms of action of estrogen receptor β in the breast, prostate, colon, and CNS
- 1Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, 3605 Cullen Blvd, Science and Engineering Research
Center Bldg 545, Houston, Texas 77204-5056, USA
2Department of Biosciences and Nutrition, Karolinska Institutet, Novum, S-141 57 Huddinge, Sweden
- Correspondence should be addressed to J-Å Gustafsson; Email: jgustafsson{at}uh.edu
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Figure 1
Schematic of the structure of the estrogen receptor (ER). The ER is composed of three main domains: the N-terminal domain (NTD), which contains the activation function 1, the DNA-binding domain (DBD), and the ligand-binding domain (LBD), containing the activation function 2. The DBDs of ERα and ERβ are highly conserved and the NTDs are the least conserved. The NTD of ERα is shorter than that of ERβ.
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Figure 2
Pathways regulated by ERβ. ERβ upon binding to its ligand 3β-Adiol/8β-VE2/DPN gets activated and transcriptionally upregulates downstream target genes such as FOXO3a and PHD2. The target genes carry ERβ binding elements such as ERE or AP1-ERE-half-site upstream or downstream of the transcriptional start site. The activated FOXO3a in turn transcriptionally upregulates PUMA, p21, and p27. PHD2 inhibits HIF1α by prolyl hydroxylation of the oxygen-dependent degradation domain (ODDD), which targets HIF1α proteins for proteasomal degradation by promoting their interaction with von Hippel–Lindau (VHL). ERβ also inhibits proliferation of genes such as c-MYC and p45Skp2 by an as yet unknown mechanism. Moreover, some of the EMT and bone metastasis genes, such as β-catenin, SLUG/SNAIL and TWIST, are opposed by ERβ.
- © 2013 Society for Endocrinology
