Interaction of transcription factor Sp1 with the promoter of the gene for the multifunctional protein disulphide isomerase polypeptide

Abstract

Protein disulphide isomerase (PDI) is a unique polypeptide which resides in the lumen of the endoplasmic reticulum and also functions as the beta-subunit of prolyl 4-hydroxylase, as a cellular thyroid hormone-binding protein, as the smaller subunit of the microsomal triacylglycerol transfer protein complex, as a dehydroascorbate reductase and as a protein that binds various peptides in a specific manner. We have recently demonstrated that the promoter of the PDI gene contains six CCAAT boxes and other elements which are needed for efficient transcription. We now demonstrate that purified human recombinant transcription factor Sp1 interacts with two perfect GGGCGG sequences and three other GC-rich elements of the PDI promoter. Sp1 also appears to participate in the regulation of PDI gene expression, since overexpression of Sp1 stimulated PDI promoter activity in HeLa cells and mutations introduced into each of these Sp1-binding sites separately reduced the promoter strength, although even the largest decrease was only about 50%. These results support our view that expression of the gene for this polypeptide with multiple functions is secured by several regulatory elements, some of which are functionally redundant.

Mechanisms of regulation of the MacMARCKS gene in macrophages by bacterial lipopolysaccharide

“…GC-rich proximal promoters are very widespread among genes expressed in other cell types. In general, multiple Sp1 binding sites are functionally redundant, with deletion of individual sites causing small reductions in activity in transient transfection [31,32]. A recent study of the mouse aprt gene suggests that some apparently redundant Sp1 elements contribute to protection of the gene against methylationdependent inactivation, a function that could only be assessed in transgenes or stable transfections.…”

Sp1 functions in a chromatin-dependent manner to augment human alpha-globin promoter activity.

“…Many studies have shown that Spl can activate transcription from various promoters (25)(26)(27)(28)(29). However, so far as we know, a chromatin-dependent effect of Spl has not been reported previously.…”

Gastrodia elata Blume and an Active Component, p-Hydroxybenzyl Alcohol Reduce Focal Ischemic Brain Injury through Antioxidant Related Gene Expressions

“…21,23) The published sequence of the promoter for the PDI gene has a consensus sequence for the antioxidant responsive element (ARE), which is activated by planar aromatic compounds like flavonoids. 34,35) Hypoxia causes the accumulation of immature protein, which may eventually initiate cell death caused by endoplasmic reticulum dysfunction. Therefore PDI could be a target for unfolded protein response-induced gene expression.…”