Estrogen-receptors corepressors

Yamamoto, Y., Wada, O., Suzawa, M., Yogiashi, Y., Yano, T., Kato, S. and Yanagisawa, J. (2001) The tamoxifen-responsive estrogen receptor a mutant D351Y shows reduced tamoxifen-dependent interaction with corepressor complexes. The Journal of Biological Chemistry, 276, 42684—42691. 

Well-documented cases exist where the estrogens inhibit the expression of some genes. These are usually transcribed by means of the constitutive activity of powerful promoters. The inhibition is a result of the steric interposition of the receptor dimer in the development region of the gene, which thereby recruits corepressors that interrupt the prior instigator effect in the absence of receptor (McKenna et al. 1999 Mester et al. 1995 Smith et al. 1997 Tora et al. 1989). 

The antiestrogenic and some of the estrogen-iike actions of SERMs can be expiained by the different conformations of the ER-a compiexes attracting novei coactivators or corepressors (CoR) (Fig. 46.5) to moduiate estrogen action at different sites, in this modei, the receptor wouid be the same at each site, yet the coactivators and corepressors wouid be distributed differentiy at different targets (130). 

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