TRANSCRIPTIONAL ACTIVATION BY THE ORPHAN NUCLEAR RECEPTOR ARP-1

被引:61
作者
MALIK, S
KARATHANASIS, S
机构
[1] Department of Cardiovascular Molecular Biology, Lederle Laboratories, Pearl River, NY 10965
关键词
D O I
10.1093/nar/23.9.1536
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
ARP-1 is a ubiquitous orphan nuclear receptor that binds to a site (site A) in the apolipoprotein Al (apoAl) liver-specific enhancer and represses its transcriptional activity in hepatoblastoma HepG2 cells. Electrophoretic mobility shift analysis of HepG2 cell nuclear extracts showed that in addition to ARP-1, site A also binds the orphan nuclear receptors Ear-2 and HNF-4. In in vitro transcription assays, Hela cell nuclear extracts which contain ARP-1 had no effect on transcription from a basal promoter linked to multiple copies of site A. However, supplementation of these extracts with excess amounts of recombinant ARP-1 resulted in significant stimulation, Supplementation of the extracts with purified polypeptides representing fusions between the ARP-1 N- or C-terminal domains and the yeast activator GAL4 DNA binding domain also stimulated transcription from a basal promoter linked to multiple GAL4 DNA binding sites. Co-immunoprecipitation assays using ARP-1-selective antibodies revealed specific physical interactions between ARP-1 and the basal transcription factor TFIIB. We conclude that ARP-1 possesses intrinsic transcription activation potential which is modulated, at least in part, by the intracellular balance of other nuclear receptors that also bind to its cognate DNA binding site.
引用
收藏
页码:1536 / 1543
页数:8
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