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Home/Research/Paper Chase/Inhibition of thyroid hormone action by a non-hormone binding c-erbA protein generated by alternative mRNA splicing.
Inhibition of thyroid hormone action by a non-hormone binding c-erbA protein generated by alternative mRNA splicing.
Nature.Feb 16, 1989;337(6208):659-61.
Koenig RJ, Lazar MA, Hodin RA, Brent GA, Larsen PR, Chin WW, Moore DD.
Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Thyroid hormone (T3) binds to a nuclear receptor protein which regulates gene expression by binding to specific DNA sequences near hormone-responsive genes. Proteins encoded by two cellular proto-oncogenes, c-erbA alpha and beta, bind T3 and can act as functional T3 receptors. In rats, alternative splicing of the alpha-gene transcript generates at least two distinct protein products, termed r-erbA alpha 1 and r-erbA alpha 2. Although these proteins bind to the same DNA sequence, r-erbA alpha 2 does not bind T3. We show here that expression of r-erbA alpha 2 inhibits the T3-dependent inductive effect of either r-erbA beta or r-erbA alpha 1 on expression of a T3-responsive test gene. Alternative splicing of the erbA alpha transcript thus generates products with opposing biological activities, suggesting a novel mechanism for the modulation of hormonal responsiveness.