title: The 4S binding protein acts as a trans-regulator of the polycyclic hydrocarbon-inducible cytochrome P450.
abstract: A model has been proposed for the induction of cytochrome P450c in liver by polycyclic hydrocarbons such as benzo(a)pyrene (BaP) and 3-methylcholanthrene (3MC). The polycyclic hydrocarbon interacts in specific, saturable, and high-affinity fashion with a rat liver cytosolic 4s binding protein. The latter enters the nucleus, complexes to 5' upstream regions of the cytochrome P450c gene, and stimulates the transcription. The 4s binding protein has been purified from rat liver and its substrate specificity has been determined. The affinity for 3MC or BaP is 1-2 mM. The binding protein has been demonstrated to complex with specific 5'-upstream regions of the P450c gene by using a filtration assay as well as exonuclease footprinting. In addition, the binding protein stimulates in vitro transcription with upstream regions of the P450c gene as template; these data confirm the hypotheses.
authors.affiliation: Department of Biochemistry, University of Nebraska Medical Center, Omaha 69105.
authors.forename: E
authors.initials: E
authors.lastname: Bresnick
authors.forename: L I
authors.initials: LI
authors.lastname: Siegel
authors.forename: W H
authors.initials: WH
authors.lastname: Houser
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity; D002352:Carrier Proteins / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D004357:Drug Synergism; D004790:Enzyme Induction; D008748:Methylcholanthrene / Q000633:toxicity; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats
chemical_list: D002352:Carrier Proteins; D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital