INTERACTION OF TRANSCRIPTION FACTOR SP1 WITH THE PROMOTER OF THE GENEFOR THE MULTIFUNCTIONAL PROTEIN DISULFIDE ISOMERASE POLYPEPTIDE

Protein disulphide isomerase (PDI) is a unique polypeptide which resid es in the lumen of the endoplasmic reticulum and also functions as the 8-subunit of prolyl 4-hydroxylase, as a cellular thyroid hormone-bind ing protein, as the smaller subunit of the microsomal triacylglycerol transfer protein complex, as a dehydroascorbate reductase and as a pro tein that binds various peptides in a specific manner. We have recentl y demonstrated that the promoter of the PDI gene contains six CCAAT bo xes and other elements which are needed for efficient transcription. W e now demonstrate that purified human recombinant transcription factor Sp1 interacts with two perfect GGGCGG sequences and three other GC-ri ch elements of the PDI promoter. Sp1 also appears to participate in th e regulation of PDI gene expression, since overexpression of Sp1 stimu lated PDI promoter activity in HeLa cells and mutations introduced int o each of these Sp1-binding sites separately reduced the promoter stre ngth, although even the largest decrease was only about 50%. These res ults support our view that expression of the gene for this polypeptide with multiple functions is secured by several regulatory elements, so me of which are functionally redundant.