A splicing variant of Steroid Receptor Coactivator-1 (SRC-1E): The major isoform of SRC-1 to mediate thyroid hormone action

Steroid Receptor Coactivator-l (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-IE, 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-IE is the major isoform of SRC-1 to mediate thyroid hormone action. (C) 1997 Academic Press.