
TY  - JOUR
A1  - Ratajczak, T. 
T1  - Protein coregulators that mediate estrogen receptor function
JF  - Reproduction, Fertility and Development
JO  - Reprod. Fertil. Dev.
Y1  - 2001
VL  - 13
IS  - 4
SP  - 221
EP  - 229
KW  - 
UR  - https://doi.org/10.1071/RD01023 
N2  - The recent discovery of estrogen receptor &#946; as a biological partner with estrogen receptor &#946; in mediating the estrogen response has come at precisely the same time as intensive research is revealing the role played by downstream coregulator proteins in linking nuclear hormone receptor activity to general transcription machinery involved in gene transcriptional activation. In what is a rapidly evolving area of research, findings to date have led to a proposed model of hormonal action, in which a receptor activated by estrogen or cell-membrane-derived phosphorylation-dependent signaling pathways promotes recruitment of selected members of the multifunctional steroid receptor coactivator family and the cointegrators, p300/CBP and P/CAF. The intrinsic histone acetylase activity mediated by these coactivator and cointegrator proteins, alters chromatin structure giving rise to increased transcriptional efficiency. On the other hand, antiestrogen-bound receptors favour the assembly of receptor-corepressor complexes containing the sequence-related corepressors N-CoR (nuclear receptor corepressor) or SMRT (silencing mediator of retinoid and thyroid hormone receptors), localizing histone deacetylase activity to the promoter and leading to transcriptional repression. The model predicts that a change in the balance between corepressor and coactivator expression in favour of coactivators, might result in antiestrogen resistance. Together with available crystal structure data for estrogen- and antiestrogen-bound receptors, these studies have provided valuable insights into events that occur subsequent to receptor interaction with specific DNA sequences and have helped define the molecular basis of estrogen and antiestrogen activity. 
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