Cloning and Characterization of RAP250, a Novel Nuclear Receptor Coactivator

• 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; 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
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.275.8.5308

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.