Molecular cloning and characterization of two novel human RXR alpha splice variants.

J Steroid Biochem Mol Biol

Advanced Technology Platform Research Laboratory, Fujisawa Pharmaceutical Co. Ltd., Tsukuba, Ibaraki 300-2698, Japan.

Published: September 2004

AI Article Synopsis

  • Two new variants of RXR alpha, named RXR alpha 2 and RXR alpha 3, were found in human cDNA libraries, lacking parts of the protein compared to the main RXR alpha 1.
  • RXR alpha 3 is expressed in brain, spleen, and prostate tissues, while RXR alpha 2's expression is very low or undetectable.
  • Both variants demonstrate transcriptional activity similar to RXR alpha 1, but show differences in response to coactivators, indicating they may have unique physiological functions.

Article Abstract

Two novel cDNAs encoding RXR alpha splice variants (RXR alpha 2 and RXR alpha 3) were identified among human full-length cDNA libraries. RXR alpha 2 and RXR alpha 3 cDNAs possess open reading frames, leading to production of proteins lacking the N-terminal 27 and 97 amino acid residues of the RXR alpha 1 product, respectively. RXR alpha 2 and RXR alpha 3 genes have respective 5'-terminal exons. RXR alpha 3 is expressed in brain, spleen and prostate whereas the expression of RXR alpha 2 was below the detectable level. Both RXR alpha 2 and RXR alpha 3 showed a level of transcriptional activity and a dose response curve against the agonist LG100268 similar to RXR alpha 1 in reporter assay for the RXR alpha homodimer or that for the heterodimer with PPAR gamma 2. However, clear differences were observed among the splice variants when dose response curves were compared by the assay in the presence of coactivators such as SRC-1 and PGC-1. These results suggest specific physiological roles of two novel human RXR alpha splice variants.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jsbmb.2004.07.001DOI Listing

Publication Analysis

Top Keywords

rxr alpha
64
rxr
16
alpha
16
splice variants
16
alpha rxr
16
alpha splice
12
novel human
8
human rxr
8
dose response
8
molecular cloning
4

Similar Publications

Small GTPase ARL4C Associated with Various Cancers Affects Microtubule Nucleation.

Biomedicines

December 2024

A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia.

The changes in the level of small GTPase ARL4C are associated with the initiation and progression of many different cancers. The content of ARL4C varies greatly between different tissues, and the induction of ARL4C expression leads to changes in cell morphology and proliferation. Although ARL4C can bind alpha-tubulin and affect intracellular transport, the role of ARL4C in the functioning of the tubulin cytoskeleton remained unclear.

View Article and Find Full Text PDF

EZH2 inhibition sensitizes retinoic acid-driven senescence in synovial sarcoma.

Cell Death Dis

November 2024

Department of Microbiology, Tumor and Cell Biology (MTC), Biomedicum, Karolinska Institutet, SE-171 65, Stockholm, Sweden.

Synovial sarcoma (SS) is driven by a unique t(18;X) chromosomal translocation resulting in expression of the SS18-SSX fusion oncoprotein, a transcriptional regulator with both activating and repressing functions. However, the manner in which SS18-SSX contributes to the development of SS is not entirely known. Here, we show that SS18-SSX drives the expression of Preferentially Expressed Antigen in Melanoma (PRAME), which is highly expressed in SS but whose function remains poorly understood.

View Article and Find Full Text PDF

Purpose: Oxysterol-binding protein-like 10 (OSBPL10) gene has been associated with reduced susceptibility to severe dengue in individuals of African descent. The aim of this study was to determine the possible effect of OSBPL10 on dengue virus (DENV) replication as well as the impact of African and European haplotypes of six OSBPL10 small nuclear polymorphisms (SNPs) on dengue multiplication and innate immune response.

Methods: We conducted gene knockdown experiments targeting OSBPL10 in THP-1 and Huh-7D12 cell lines, followed by a DENV-2 replication assay.

View Article and Find Full Text PDF
Article Synopsis
  • The activation of nuclear retinoid X receptors (RXRs) involves releasing corepressors and recruiting coactivators, influencing gene activation or repression.
  • Research identified a synthetic agonist that significantly increases the binding of PGC1α (a coactivator) to RXR, unlike the natural ligand 9-cis retinoic acid.
  • The study produced three related RXR agonists with varying abilities to enhance PGC1α recruitment, suggesting potential new therapies through targeted RXR-PGC1α interactions via selective coregulator modulation.
View Article and Find Full Text PDF
Article Synopsis
  • * Deleting AMPK in atrial tissue shifts metabolism from fatty acid oxidation to pyruvate oxidation, resulting in lower levels of long-chain fatty acyl-CoAs and reduced expression of proteins that help take in and process fatty acids.
  • * The study shows that AMPK is essential for maintaining atrial metabolic balance, and its deletion disrupts the PGC1-α/PPARα signaling pathway, which may lead to heart remodeling and increased risk of arrhythmias.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!