Inhibition of nuclear hormone receptor activity by calreticulin

Nature. 1994 Feb 3;367(6462):480-3. doi: 10.1038/367480a0.


We have shown that a polypeptide of M(r) 60,000 (60K) that shares N-terminal homology with a calcium-binding protein, calreticulin, can bind to an amino-acid sequence motif, KXGFFKR, found in the cytoplasmic domains of all integrin alpha-subunits. The homologous amino-acid sequence, KXFFKR (where X is either G, A or V), is also present in the DNA-binding domain of all known members of the steroid hormone receptor family; amino acids in this sequence make direct contact with nucleotides in their DNA-responsive elements and are crucial for DNA binding. Here we show that both the 60K protein (p60), purified on a KLGFFKR-Sepharose affinity matrix, and recombinant calreticulin can inhibit the binding of androgen receptor to its hormone-responsive DNA element in a KXFFKR-sequence-specific manner. Calreticulin can also inhibit androgen receptor and retinoic acid receptor transcriptional activities in vivo, as well as retinoic acid-induced neuronal differentiation. Our results indicate that calreticulin can act as an important modulator of the regulation of gene transcription by nuclear hormone receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Androgen Receptor Antagonists*
  • Animals
  • Base Sequence
  • Calcium-Binding Proteins / pharmacology*
  • Calreticulin
  • Cell Line
  • Cell Nucleus / metabolism
  • DNA / metabolism
  • Gene Expression Regulation / physiology
  • Integrins / metabolism
  • Molecular Sequence Data
  • Rats
  • Receptors, Androgen / metabolism
  • Receptors, Retinoic Acid / metabolism
  • Ribonucleoproteins / pharmacology*
  • Tumor Cells, Cultured
  • Vero Cells


  • Androgen Receptor Antagonists
  • Calcium-Binding Proteins
  • Calreticulin
  • Integrins
  • Receptors, Androgen
  • Receptors, Retinoic Acid
  • Ribonucleoproteins
  • DNA