Structure and Function of the Nuclear Receptor Constitutive Androstane Receptor

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
Yoshio Inouye

Abstract

Animal defense mechanisms against both endogenous and exogenous toxic compounds function mainly through receptor-type transcription factors, including the constitutive androstane receptor (CAR). Following xenobiotic stimulation, CAR translocates into the nucleus and transactivates its target genes including oxygenic and conjugative enzymes and transporters in hepatocytes. We identified subcellular localization signals in the rat CAR: two nuclear localization signals (NLS1 and 2); two nuclear export signals (NES1 and 2); and a cytoplasmic retention region. The nuclear import of CAR is regulated by the importin-Ran system and microtubule network. Five splice variants (SV1-5) were identified in rat liver in addition to wild-type CAR. When expressed in immortalized cells, their artificial transcripts were inactive as transcription factors. A CAR mutant with three consecutive alanine residues inserted into the ligand-binding domain of CAR showed ligand-dependent activation of target genes in immortalized cells, which is in marked contrast to the constitutive transactivating nature of wild-type CAR. Using this assay system, androstenol and clotrimazole, both of which are inverse agonists of CAR, were classified as an antagonist and w...Continue Reading

References

Jan 1, 1995·Annual Review of Biochemistry·L I Davis
Sep 20, 1997·The Journal of Biological Chemistry·H S ChoiD D Moore
Feb 26, 1999·The Journal of Biological Chemistry·T SueyoshiM Negishi
Jun 28, 2001·Physiological Reviews·A Aranda, A Pascual
Jul 18, 2002·Nature Reviews. Drug Discovery·Timothy M Willson, Steven A Kliewer
Aug 16, 2002·Molecular Pharmacology·Stephen S FergusonJoyce A Goldstein
Aug 29, 2002·Nature·Steven M Reppert, David R Weaver
Dec 6, 2002·The Journal of Biological Chemistry·Ramji R RajendranBenita S Katzenellenbogen
Feb 8, 2003·Biochimica Et Biophysica Acta·John T MooreSteve A Kliewer
Mar 15, 2003·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·K MaekawaJ Sawada
Jun 12, 2003·Nucleic Acids Research·Scott S AuerbachCurtis J Omiecinski
Oct 22, 2003·Molecular Genetics and Metabolism·Rajesh S SavkurThomas P Burris
Jun 15, 2004·The Journal of Pharmacology and Experimental Therapeutics·Jatinder K LambaErin Schuetz
Aug 31, 2004·Nuclear Receptor·Yuichiro KannoYoshio Inouye
Feb 12, 2005·The Journal of Organic Chemistry·Kun WeiTamotsu Nikaido
Nov 8, 2005·Biological & Pharmaceutical Bulletin·Yuichiro KannoYoshio Inouye
Jul 1, 2006·American Journal of Respiratory Cell and Molecular Biology·Tao TaoFeige Kaplan
Dec 30, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Scott S AuerbachCurtis J Omiecinski
Jan 11, 2007·Proceedings of the National Academy of Sciences of the United States of America·Sharon M BlättlerUrs A Meyer
May 10, 2007·Biochimica Et Biophysica Acta·Yuichiro KannoYoshio Inouye
May 29, 2007·Drug Discovery Today·Yanhong Shi
Sep 4, 2007·FEBS Letters·Hélène Duez, Bart Staels
Feb 29, 2008·Drug Metabolism and Pharmacokinetics·Yoshihiro KonnoSusumu Kodama
May 19, 2010·Biochimica Et Biophysica Acta·Yuichiro KannoYoshio Inouye
May 21, 2010·Molecular Biology of the Cell·Wanqiao ZhangFuchu He
Aug 6, 2010·The Journal of Toxicological Sciences·Yuichiro Kanno, Yoshio Inouye
Mar 5, 2011·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yuichiro Kanno, Yoshio Inouye
Aug 23, 2012·Biochemical and Biophysical Research Communications·Yuichiro KannoYoshio Inouye

❮ Previous
Next ❯

Citations

Jun 1, 2016·Toxicon : Official Journal of the International Society on Toxinology·Md Sajid GhufranSantosh R Kanade
Oct 10, 2021·Bulletin of Experimental Biology and Medicine·A V Shchul'kinE N Yakusheva

❮ 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.

© 2021 Meta ULC. All rights reserved