Inhibition of nuclear hormone receptor activity by calreticulin.

Dedhar S, Rennie PS, Shago M, Hagesteijn CY, Yang H, Filmus J, Hawley RG, Bruchovsky N, Cheng H, Matusik RJ
Nature. 1994 367 (6462): 480-3

PMID: 8107809 · 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.

MeSH Terms (18)

Amino Acid Sequence Androgen Receptor Antagonists 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

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