CAR, driving into the future

Mol Endocrinol. 2004 Jul;18(7):1589-98. doi: 10.1210/me.2003-0397. Epub 2004 Feb 26.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Nucleus / metabolism
  • Endocrine System / metabolism
  • Endocrine System Diseases / metabolism
  • HSP90 Heat-Shock Proteins / metabolism
  • Homeostasis / physiology
  • Humans
  • Liver / pathology
  • Liver / physiology
  • Phosphoprotein Phosphatases / metabolism
  • Protein Transport
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Transcription Factors / chemistry
  • Transcription Factors / physiology*

Substances

  • HSP90 Heat-Shock Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • constitutive androstane receptor
  • Phosphoprotein Phosphatases