CAR, driving into the future.
The nuclear orphan receptor CAR is active in the absence of ligand with the unique capability to be further regulated by activators. A number of these activators, including phenobarbital, do not directly bind to the receptor. Considered a xenobiotic sensing receptor, CAR transcriptionally modifies the expression of genes involved in the metabolism and elimination of xenobiotics and steroids in response to these compounds and other cellular metabolites. Its hepatic expression pattern endows the liver with the ability to protect against not only exogenous but also endogenous insults. The mechanism of CAR activation is complex, involving translocation from the cytoplasm to the nucleus in the presence of activators, followed by further activation steps in the nucleus. Although this mechanism remains under investigation, we have summarized here the cellular signaling pathways elucidated so far and speculate on the mechanism by which CAR activators regulate gene expression through this network.
Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Karen
K
Swales
Masahiko
M
Negishi
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D000090702:Constitutive Androstane Receptor; D004703:Endocrine System / Q000378:metabolism; D004700:Endocrine System Diseases / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008099:Liver / Q000473:pathology / Q000502:physiology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry / Q000502:physiology*
D000090702:Constitutive Androstane Receptor; D018841:HSP90 Heat-Shock Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D010749:Phosphoprotein Phosphatases