Intron Retention Generates a Novel Isoform of the Murine Vitamin D Receptor That Acts in a Dominant Negative Way on the Vitamin D Signaling Pathway
| Autor: | Tadao Hasegawa, Koichiro Matsuda, Yoshikatsu Uematsu, Hideyuki Harada, Takuya Kitamoto, Shigeaki Kato, Shoichi Masushige, Kanae Ebihara, Yoshikazu Masuhiro, Miyuki Suzawa, Tatsuya Yoshizawa, Toshio Ono |
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| Rok vydání: | 1996 |
| Předmět: |
Chloramphenicol O-Acetyltransferase
Gene isoform Transcription Genetic Receptors Retinoic Acid Recombinant Fusion Proteins Dominant Negative Receptor Molecular Sequence Data Restriction Mapping Retinoic acid Biology Retinoid X receptor Kidney Transfection Polymerase Chain Reaction Calcitriol receptor chemistry.chemical_compound Calcitriol Vitamin D Response Element Animals Humans Amino Acid Sequence Intestinal Mucosa Vitamin D Molecular Biology Base Sequence Alternative splicing Cell Biology Embryo Mammalian Molecular biology Introns Rats VDRE Alternative Splicing Retinoid X Receptors chemistry Receptors Calcitriol Oligonucleotide Probes Research Article HeLa Cells Signal Transduction Transcription Factors |
| Zdroj: | Molecular and Cellular Biology. 16:3393-3400 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.16.7.3393 |
| Popis: | We identified and characterized a novel rat vitamin D receptor isoform (rVDR1), which retains intron 8 of the canonical VDR (rVDR0) during alternative splicing. In this isoform protein directed by the stop codon in this newly identified exon, a part of the ligand binding domain (86 amino acids) is truncated at the C-terminal end but contains 19 extra amino acids. The rVDR1 transcript was expressed at a level 1/15 to 1/20 of that of rVDR0 in the kidney and intestine in adult rats but not in embryos. The recombinant rVDR1 protein showed no ligand binding activity. Homo- and heterodimers of the recombinant rVDR0 and rVDR1 proteins bound to a consensus vitamin D response element (VDRE) but not to consensus response elements for thyroid hormone and retinoic acid. However, unlike rVDR0, rVDR1 did not form a heterodimeric complex with RXR on the VDRE. A transient expression assay showed that this isoform acted as a dominant negative receptor against rVDR0 transactivation. Interestingly, the dominant negative activities of rVDR1 differed among VDREs. Thus, the present study indicates that this new VDR isoform negatively modulates the vitamin D signaling pathway, through a particular set of target genes. |
| Databáze: | OpenAIRE |
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