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 in vivo 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.
Caira
F
F
Department of Biosciences at Novum, Karolinska Institutet, S-14157 Huddinge, Sweden.
Antonson
P
P
Pelto-Huikko
M
M
Treuter
E
E
Gustafsson
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics*; D002467:Cell Nucleus / Q000737:chemistry*; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D015723:Gene Library; D006801:Humans; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D056918:Nuclear Receptor Coactivators; D010957:Plasmids; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; C486559:NCOA6 protein, human; C405683:Ncoa6 protein, mouse; C486560:Ncoa6 protein, rat; D056918:Nuclear Receptor Coactivators; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors