Transcriptional control of hepatocanalicular transporter gene expression.
Transport processes for larger organic solutes at the canalicular membrane are mainly driven by members of the superfamily of ATP-binding cassette (ABC) transporters. The functions of these transporters range from bile component secretion to xenobiotica and phase II-conjugate export. The transcriptional control of the expression of their respective genes differs, and this may be to guarantee tissue specificity, effective response to stress, or changes in substrate concentrations. Inside the nucleus, the concentration of competing and specifically activated transcription factors determines the transcriptional activation in transporter gene expression. Some transcription factors function as sensors for metabolites (LXR, FXR, CAR, SREBP, PPARs), xenobiotics (PPARs, PXR), oxidative stress (NF-kappa B, AP-1), or DNA damage (p53). Changes in their nuclear concentrations and activity will influence the transcription rates of the respective target genes that contain specific responsive elements in their 5'-promoter/enhancer DNA sequences. Until now little was known about the transcriptional control of most ABC transporter proteins. However, due to the enormous progress in molecular biology, many tools have become recently available to study and understand the "battle inside the nucleus" with respect to hepatic transporter gene expression.
Müller
M
M
Division of Gastroenterology and Hepatology, University Hospital Groningen, The Netherlands. m.muller@med.rug.nl
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D027321:Anion Transport Proteins; D001646:Bile / Q000378:metabolism; D001648:Bile Canaliculi / Q000378:metabolism*; D002352:Carrier Proteins / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D008099:Liver / Q000378:metabolism; D051381:Rats; D013312:Stress, Physiological / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D027321:Anion Transport Proteins; D002352:Carrier Proteins; D014157:Transcription Factors