Nucleic Acids Research, Vol 26, Issue 15 3505-3512, Copyright © 1998 by Oxford University Press
S Ogawa, S Inoue, T Watanabe, A Orimo, T Hosoi, Y Ouchi and M Muramatsu
We have identified and characterized a novel human estrogen receptor (ER)
beta isoform, ERbetacx, which is truncated at the C-terminal region but has
an extra 26 amino acids due to alternative splicing. The ERbetacx
transcript is expressed in testis, ovary, thymus and prostate as well as in
human cultured cell lines such as HEC-1, HOS-TE85 and Saos-2 cells.
ERbetacx protein is also immunodetectable in these human cells. Biochemical
analysis reveals that the average dissociation constants ( K d) of ERalpha
and ERbeta for 17beta-estradiol (E2) are 0.2 and 0.6 nM respectively, but
ERbetacx has no ligand binding ability. ERalpha and ERbeta proteins bind to
the estrogen response element, whereas ERbetacx does not form any shifted
complex in gel shift assays. In a transient expression assay, ERbetacx
shows no ligand- dependent transactivation ability of a basal promoter and
also cannot interact with a cofactor, TIF1alpha, in the presence or absence
of E2. ERbetacx preferentially forms a heterodimer with ERalpha rather than
that with ERbeta, inhibiting DNA binding by ERalpha. Interestingly,
however, it shows a significant dominant negative activity only against
ERalpha transactivation. Thus, this study indicates that ERbetacx
potentially inhibits ERalpha-mediated estrogen action and that alternative
splicing of the C-terminal region and its inhibitory properties are
characteristic of several members of nuclear receptor isoforms.
ARTICLES
Molecular cloning and characterization of human estrogen receptor betacx: a potential inhibitor ofestrogen action in human
Department of Biochemistry, Saitama Medical School, 38 Morohongo, Moroyama-machi, Iruma-gun,Saitama 350-0495, Japan.
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S. A. W. Fuqua, R. Schiff, I. Parra, W. E. Friedrichs, J.-L. Su, D. D. McKee, K. Slentz-Kesler, L. B. Moore, T. M. Willson, and J. T. Moore Expression of Wild-Type Estrogen Receptor {{beta}} and Variant Isoforms in Human Breast Cancer Cancer Res., November 1, 1999; 59(21): 5425 - 5428. [Abstract] [Full Text] [PDF]
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