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Molecular and Cellular Biology, April 2000, p. 2411-2422, Vol. 20, No. 7
Division of Biochemistry, Biozentrum of the
University of Basel, CH-4056 Basel, Switzerland
Received 1 November 1999/Returned for modification 12 December
1999/Accepted 3 January 2000
Steroid receptors mediate responses to lipophilic hormones in a
tissue- and ligand-specific manner. To identify nonreceptor proteins
that confer specificity or regulate steroid signaling, we screened a
human cDNA library in a steroid-responsive yeast strain. One of the
identified cDNAs, isolated in the screen as ligand effect modulator 6, showed no homology to yeast or Caenorhabditis elegans
proteins but high similarity to the recently described mouse
coactivator PGC-1 and was accordingly termed hPGC-1. The hPGC-1 DNA
encodes a nuclear protein that is expressed in a tissue-specific manner
and carries novel motifs for transcriptional regulators. The expression
of hPGC-1 in mammalian cells enhanced potently the transcriptional
response to several steroids in a receptor-specific manner.
hPGC-1-mediated enhancement required the receptor hormone-binding domain and was dependent on agonist ligands. Functional analysis of
hPGC-1 revealed two domains that interact with steroid receptors in a
hormone-dependent manner, a potent transcriptional activation function,
and a putative dimerization domain. Our findings suggest a regulatory
function for hPGC-1 as a tissue-specific coactivator for a subset of
nuclear receptors.
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
A Tissue-Specific Coactivator of Steroid Receptors,
Identified in a Functional Genetic Screen
*
Corresponding author. Mailing address: Division of
Biochemistry, Biozentrum of the University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland. Phone: 41 61 267 2162. Fax: 41 61 267 2149. E-mail: anastasia.kralli{at}unibas.ch.
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