Inhibition of nuclear hormone receptor activity by calreticulin.

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.
Mesh Terms:
Amino Acid Sequence, Animals, Base Sequence, Calcium-Binding Proteins, Calreticulin, Cell Line, Cell Nucleus, DNA, Gene Expression Regulation, Integrins, Molecular Sequence Data, Rats, Receptors, Androgen, Receptors, Retinoic Acid, Ribonucleoproteins, Tumor Cells, Cultured, Vero Cells
Nature
Date: Feb. 03, 1994
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