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Inhibition of nuclear hormone receptor activity by calreticulin

Abstract

WE have shown that a polypeptide of Mr 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 α-subunits1. 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 family2; amino acids in this sequence make direct contact with nucleotides in their DNA-responsive elements and are crucial for DNA binding3. 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.

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Dedhar, S., Rennie, P., Shago, M. et al. Inhibition of nuclear hormone receptor activity by calreticulin. Nature 367, 480–483 (1994). https://doi.org/10.1038/367480a0

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