Cloning and Characterization of RAP250, a Novel Nuclear Receptor Coactivator

Ligand-induced transcriptional activation of gene expression by nuclear receptors is dependent on recruitment of coactivators as intermediary factors. The present work describes the cloning and characterization of RAP250, a novel human nuclear receptor coactivator. The results of in vitro and invivo...

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Bibliographic Details
Published in:The Journal of biological chemistry 2000-02, Vol.275 (8), p.5308-5317
Main Authors: Caira, Françoise, Antonson, Per, Pelto-Huikko, Markku, Treuter, Eckardt, Gustafsson, Jan-Åke
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Carrier Proteins - chemistry
Carrier Proteins - genetics
Cell Nucleus - chemistry
COS Cells
DNA, Complementary - metabolism
Female
Gene Library
Humans
In Situ Hybridization
Intracellular Signaling Peptides and Proteins
Male
Medicin och hälsovetenskap
Mice
Molecular Sequence Data
nuclear receptor coactivator
Nuclear Receptor Coactivators
Plasmids
RAP250 protein
Rats
Rats, Sprague-Dawley
Receptors, Cytoplasmic and Nuclear - metabolism
Receptors, Estrogen - metabolism
Receptors, Thyroid Hormone - metabolism
Recombinant Fusion Proteins - metabolism
RNA, Messenger - metabolism
Sequence Homology, Amino Acid
Tissue Distribution
Transcription Factors - metabolism
Two-Hybrid System Techniques
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Summary:Ligand-induced transcriptional activation of gene expression by nuclear receptors is dependent on recruitment of coactivators as intermediary factors. The present work describes the cloning and characterization of RAP250, a novel human nuclear receptor coactivator. The results of in vitro and invivo experiments indicate that the interaction of RAP250 with nuclear receptors is ligand-dependent or ligand-enhanced depending on the nuclear receptor and involves only one short LXXLL motif called nuclear receptor box. Transient transfection assays further demonstrate that RAP250 has a large intrinsic glutamine-rich activation domain and can significantly enhance the transcriptional activity of several nuclear receptors, acting as a coactivator. Interestingly, Northern blot and in situ hybridization analyses reveal that RAP250 is widely expressed with the highest expression in reproductive organs (testis, prostate and ovary) and brain. Together, our data suggest that RAP250 may play an important role in mammalian gene expression mediated by nuclear receptor.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.275.8.5308