title: Inhibition of thyroid hormone action by a non-hormone binding c-erbA protein generated by alternative mRNA splicing.
abstract: 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.
authors.affiliation: Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: R J
authors.initials: RJ
authors.lastname: Koenig
authors.forename: M A
authors.initials: MA
authors.lastname: Lazar
authors.forename: R A
authors.initials: RA
authors.lastname: Hodin
authors.forename: G A
authors.initials: GA
authors.lastname: Brent
authors.forename: P R
authors.initials: PR
authors.lastname: Larsen
authors.forename: W W
authors.initials: WW
authors.lastname: Chin
authors.forename: D D
authors.initials: DD
authors.lastname: Moore
mesh_terms: D000818:Animals; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D005822:Genetic Vectors; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics*; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D014162:Transfection / Q000187:drug effects*; D014284:Triiodothyronine / Q000037:antagonists & inhibitors* / Q000494:pharmacology
chemical_list: D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D015500:Chloramphenicol O-Acetyltransferase