ABC-ATPases as Regulatory Transporters for NHRs: chemical sensors for endogenous metabolites and xenobiotics

Transporter gene expression is under the control of nuclear hormone receptors (NHRs) such as PPARa (Peroxisome Proliferator Activated Receptor), LXR (Liver X Receptor), FXR (Farnexoid X Receptor), SREBP (Sterol Responsive Element Binding Protein). NHRs bind directly to responsive elements on DNA and are involved in the control of gene expression in stress response induced by the internal and external environment. It has been proposed that ABC-transporters are regulatory transporters that control the intracellular level of ligands for NHRs. As such they are an integral part of the cellular chemical sensor mechanism for endogenous metabolites and exogenous "chemical invaders" or xenobiotics.

Used with permission from M. Muller.

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References:

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Meier, P.J., and Stieger, B., Bile salt transporters. Annu. Rev. Physiol., 64, 635-661 (2002).

Fitzgerald, M.L., et al., Nuclear hormone receptors and cholesterol trafficking: the orphans find a new home. J. Mol. Med., 80, 271-281 (2002).