Modulation of gene expression by calreticulin binding to the glucocorticoid receptor.

Calreticulin is a multifunctional protein that acts as a major Ca(2+)-binding (storage) protein in the lumen of the endoplasmic reticulum. It is also found in the nucleus, suggesting that it may have a role in transcription regulation. Calreticulin has been reported to bind to the synthetic peptide KLGFFKR, which is ...
almost identical to an amino-acid sequence in the DNA-binding domain of the superfamily of nuclear receptors. Could calreticulin interact with the DNA-binding domain of these receptors and affect their function? Here we report that the amino terminus of calreticulin interacts with the DNA-binding domain of the glucocorticoid receptor and prevents the receptor from binding to its specific glucocorticoid response element. Overexpression of calreticulin in mouse L fibroblasts inhibits glucocorticoid-response-mediated transcriptional activation of a glucocorticoid-sensitive reporter gene and of the endogenous, glucocorticoid-sensitive gene encoding cytochrome P450. Together these results indicate that calreticulin may be important in gene transcription, regulating the glucocorticoid receptor and perhaps other members of the super-family of nuclear receptors.
Mesh Terms:
Amino Acid Sequence, Animals, Base Sequence, Binding Sites, Calcium-Binding Proteins, Calreticulin, Cell Nucleus, Cytochrome P-450 Enzyme System, DNA, DNA Primers, Escherichia coli, Gene Expression Regulation, Genes, Reporter, Glutathione Transferase, Humans, L Cells (Cell Line), Mice, Molecular Sequence Data, Receptors, Glucocorticoid, Recombinant Fusion Proteins, Ribonucleoproteins
Nature
Date: Feb. 03, 1994
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