Ubiquitous Receptor: A Receptor That Modulates Gene Activation by Retinoic Acid and Thyroid Hormone Receptors

• Published in: Proceedings of the National Academy of Sciences - PNAS 1994-11, Vol.91 (23), p.10809-10813
• Main Authors: Song, Ching, Kokontis, John M., Hiipakka, Richard A., Liao, Shutsung
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Cloning, Molecular; Complementary DNA; COS cells; Deoxyribonucleic acid; DNA; DNA Primers - chemistry; DNA, Complementary - genetics; Gels; Gene Expression Regulation; Genes; Hormones; Humans; Medical research; Molecular Sequence Data; Nuclear receptors; Plasmids; Rats; Receptors; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Retinoic Acid - physiology; Receptors, Thyroid Hormone - physiology; Reporter genes; Response elements; Retinoid X Receptors; RNA; RNA, Messenger - genetics; Sequence Alignment; Sequence Homology, Amino Acid; Thyroid gland; Tissue Distribution; Transcription Factors - genetics; Transcription Factors - physiology; Transcriptional Activation
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.23.10809

The cDNA for a member of the nuclear receptor family was cloned and named ubiquitous receptor (UR), since UR protein and mRNA are detected in many cell types. Rat UR/human retinoid X receptor α (hRXRα) heterodimers bound preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence AGGTCA and 4-nt spacing (DR-4). Coexpression of UR in COS-1 cells inhibited the stimulation of chloramphenicol acetyltransferase (CAT) reporter gene expression by hRXRα and human retinoic acid receptor α in the presence of all-trans-retinoic acid when DR-4 (but not DR-5) was present upstream of the promoter of a CAT reporter gene (DR-4-CAT). UR expression also inhibited the activation of a DR-4-CAT reporter gene by hRXRα and 9-cis-retinoic acid or by thyroid hormone receptor β in the presence of thyroid hormone. However, in the absence of 9-cis-retinoic acid, UR in combination with hRXRα stimulated DR-4-CAT expression. Coexpression of thyroid hormone receptor markedly reduced this stimulation in the absence of thyroid hormone. UR may play an important role in normal growth and differentiation by modulating gene activation in retinoic acid and thyroid hormone signaling pathways.