[Regulation of thyroid hormone binding protein/protein disulfide isomerase (T3BP/PDI) gene expression]

PDI catalyzes the formation of disulfide bonds and plays a central role in the correct folding of nascent polypeptides. In addition, it is multifunctional and may participate in more complex enzyme systems, catalyzing other protein modification. PDI is also known to bind T3. The human T3BP/PDI gene, located in the chromosome 17, consists of a transcribed part of 16.5 kb and the protein coding sequence is divided into 11 exons. The analysis of the 5'-flanking region revealed several putative transcriptional elements, including a TATA box, 6 CCAAT elements and 5 GC-rich regions, each of which is related to the promoter activity. The mechanism of T3BP/PDI gene expression is, however, unknown. Treatment with T4, PTU, insulin and fasting-refeeding induced different responses in T3BP/PDI mRNA and protein levels among various tissues. Recent studies revealed that the unfolded proteins, accumulated in the ER lumen, might stimulate the gene expression of a set of protein including BiP, GRp94 and PDI, which is required for proper protein folding and assembling. The meaning of T3-binding activity of PDI is open for further study.