Xenobiotic metabolism in the fourth dimension: PARtners in time.
A significant portion of the transcriptome in mammals, including the PAR bZIP transcription factors DBP, HLF, and TEF, is under circadian clock control. In this issue of Cell Metabolism, Gachon and colleagues (Gachon et al., 2006) show that disruption of these three genes in mice alters gene expression patterns of many proteins involved in drug metabolism and in liver and kidney responses to xenobiotic agents. Triple mutant mice have severe physiological deficits, including increased hypersensitivity to xenobiotic agents and premature aging, highlighting the profound effect the circadian clock has on this important response system.
Green
Carla B
CB
Department of Biology, University of Virginia, Charlottesville, Virginia 22904, USA.
Takahashi
Joseph S
JS
D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001683:Biological Clocks / Q000235:genetics / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology; D006801:Humans; D051379:Mice; D013997:Time Factors; D015262:Xenobiotics / Q000378:metabolism*
D050976:Basic-Leucine Zipper Transcription Factors; D015262:Xenobiotics