title: A splicing variant of Steroid Receptor Coactivator-1 (SRC-1E): the major isoform of SRC-1 to mediate thyroid hormone action.
abstract: Steroid Receptor Coactivator-1 (SRC-1) interacts with nuclear receptors only when they are bound to the ligands and enhance the transactivation. We identified splicing variants encoding three isoforms, SRC-1, SRC-1(-Q), and SRC-1E, generated by alternative usage of an exon(s) and splicing acceptor sites. RT-PCR analysis showed that SRC-1E was more abundantly expressed than SRC-1 or SRC-1(-Q) at the mRNA level in all the cell lines tested. SRC-1E lacks 56 amino acids of SRC-1 and has unique 14 amino acids at the carboxyl terminus, while SRC-1(-Q) differs from SRC-1 by deletion of only one glutamine residue. Since the C-terminal domain of SRC-1 has been shown to be involved in the interaction with nuclear receptors, the enhancement of transactivation by these three isoforms was tested. SRC-1E enhanced thyroid hormone dependent transactivation of reporter gene expression more profoundly than SRC-1 or SRC-1(-Q). Taken together, it was suggested that SRC-1E is the major isoform of SRC-1 to mediate thyroid hormone action.
authors.affiliation: Department of Endocrinology and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Chikusa-ku, Japan. hayashiy@endeavor.riem.nagoya-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
authors.forename: S
authors.initials: S
authors.lastname: Ohmori
authors.forename: T
authors.initials: T
authors.lastname: Ito
authors.forename: H
authors.initials: H
authors.lastname: Seo
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D051548:Histone Acetyltransferases; D006801:Humans; D008969:Molecular Sequence Data; D056920:Nuclear Receptor Coactivator 1; D012313:RNA / Q000032:analysis; D012326:RNA Splicing; D013963:Thyroid Hormones / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D013963:Thyroid Hormones; D014157:Transcription Factors; D012313:RNA; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1