The Mechanism for the Induction of Cytochrome P450 2B Subfamily: Progress of Research and Future Problem.

Research history and recent progress on the mechanism by which xenobiotics induce cytochromes P450 belonging to the CYP2B subfamily are briefly reviewed. One of the major interests focused here is that what is the initial target site for exogenous inducers? In this topics, we discussed the validity of the concept for the receptor-mediated induction, and for a mechanism in which xenobiotic inducers cancel the effect with endogenous suppressors. Recent studies have revealed a crucial role of nuclear receptors, CAR (Constitutive Androstane Receptor) and RXR (Retinoid X-Receptor), in trans-activating a specific region located 5'-Upstream of the CYP2B genes. We also reviewed the role of DNA elements participating in transactivation, and those of the trans-factors involving not only CAR/RXR but also other factors such as Barbie box and RBP-Jκ.