Modulation of gene expression by calreticulin binding to the glucocorticoid receptor

Nature. 1994 Feb 3;367(6462):476-80. doi: 10.1038/367476a0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Calcium-Binding Proteins / metabolism*
  • Calcium-Binding Proteins / physiology
  • Calreticulin
  • Cell Nucleus / metabolism
  • Cytochrome P-450 Enzyme System / genetics
  • DNA / metabolism
  • DNA Primers
  • Escherichia coli
  • Gene Expression Regulation / physiology*
  • Genes, Reporter
  • Glutathione Transferase / genetics
  • Humans
  • L Cells
  • Mice
  • Molecular Sequence Data
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Ribonucleoproteins / metabolism*
  • Ribonucleoproteins / physiology


  • Calcium-Binding Proteins
  • Calreticulin
  • DNA Primers
  • Receptors, Glucocorticoid
  • Recombinant Fusion Proteins
  • Ribonucleoproteins
  • DNA
  • Cytochrome P-450 Enzyme System
  • Glutathione Transferase