PMID: 8001825Dec 15, 1994Paper

Retinoid-dependent in vitro transcription mediated by the RXR/RAR heterodimer

Genes & Development
R ValcárcelH G Stunnenberg

Abstract

The effects of retinoids on gene regulation are mediated by retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Here, we provide the first biochemical evidence that, in vitro, ligand governs the transcriptional activity of RXR alpha/RAR alpha by inducing conformational changes in the ligand-binding domains. Using limited proteolytic digestion we show that binding of the cognate ligand causes a conformational change in the carboxy-terminal part of the receptor. We also show that recombinant RXR alpha/RAR alpha is partially active in the absence of exogenously added ligand. Trans-activation depends critically on the ligand-dependent transcriptional activation function AF-2 of RAR alpha. Full activation by recombinant RXR alpha/RAR alpha, however, requires the addition of either all-trans RA, 9-cis RA, or other RAR-specific agonists, whereas an RAR alpha-specific antagonist abolishes trans-activation. Intriguingly, the ligand-dependent AF-2 of RXR does not contribute to the level of transcription from the RAR beta 2 promoter in vitro even when the cognate ligand (9-cis RA) is bound. Thus, the major role of RXR in trans-activation of the RAR beta 2 promoter is to serve as an auxiliary factor required for the binding of ...Continue Reading

Citations

Dec 23, 1999·European Journal of Pharmacology·R Pakala, C R Benedict
Feb 28, 1997·Biochimica Et Biophysica Acta·R ValcárcelH G Stunnenberg
Nov 28, 2002·Breast Cancer Research and Treatment·Qifeng YangKennichi Kakudo
May 11, 1995·Nucleic Acids Research·S Malik, S Karathanasis
Oct 23, 1997·Proceedings of the National Academy of Sciences of the United States of America·S MinucciK Ozato
Mar 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·C LiR M Evans
Dec 13, 2006·Life Sciences·Tomoko KodaMasatoshi Morita
Mar 8, 1996·Chemico-biological Interactions·D M Kochhar ChandraratnaAS
Aug 25, 1995·Biochemical Pharmacology·H JiangD M Kochhar
Dec 15, 1995·Cell·D J Mangelsdorf, R M Evans
Aug 29, 1996·Nature·J Y ChenH Gronemeyer
Oct 27, 1997·The Journal of Biological Chemistry·J A Recio, A Aranda
Sep 16, 1998·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·T PalominoA Aranda
Oct 29, 1997·Molecular and Cellular Biology·N BhattacharyyaK Ozato

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.