Transcriptional regulation by thyroid hormone of an mRNA homologous to a protease inhibitor.

Abstract

We have previously cloned a cDNA of a rat liver mRNA, designated 4-12B, markedly induced by triiodothyronine (T3) at a pretranslational level [Magnuson, M.A., Dozin, B., & Nikodem, V.M. (1985) J. Biol. Chem. 260, 5906-5912]. Here we show that this hormonal effect is due in part to an increase of the rate of transcription of the 4-12B gene. In addition, the nucleotide sequence of 4-12B cDNA has been determined, revealing significant similarity with the sequences of the superfamily of serine protease inhibitors and a very high homology with contrapsin, a mouse serum trypsin inhibitor, at the level of nucleotide and amino acid sequence (77.9 and 66.8%, respectively). The optimized alignment of the putative reactive center region of 4-12B with four related members of this superfamily revealed that lysine-serine residues are located at the reactive site or adjacent to it, thus suggesting that the triiodothyronine-regulated rat 4-12B mRNA might code for a protease inhibitor with trypsin-like specificity. Although not enough data are presently available to assign definitively antitryptic activity to this protein, the high degree of similarity with members of the superfamily of serine protease inhibitors leaves no doubt that 4-12B is a member of this superfamily.