The regulation of the family of UDP glucuronosyltransferase enzymes is being studied by means of DNA, RNA and protein chemistry. Different members of the transferase system are known to be induced by a number of different types of effector compounds; several such compounds used in these studies are phenobarbital, clofibrate, perfluorooctanoic acid, benzo[a]pyrene and 3-methylcholanthrene. A number of mouse transferase clones have been isolated and identified by hybridization to rat transferase clones and/or by immunoreactivity of protein expressed by a recombinant Lambdagt11 system. A clone UDPGT-m-1 encoding the complete amino acid (530) sequence for mouse transferase is shown to contain an N-terminus membrane-insertion signal peptide, two potential glycosylation sites, and a carboxy-terminus membrane-spanning region. UDPGTm-1 encodes a 2200-nt mRNA and cross-hybridizes to a 2000-nt mRNA due to sequence homology in the 5' portion of the insert. The two mRNAs are induced 2.5- to 5-fold by the barbiturate phenobarbital, the hypolipidemic agents clofibrate and perfluorooctanoic acid, and the aromatic hydrocarbon benzo[a]pyrene. In a parallel manner, the same compounds induce bilirubin trnsferasse activity. UDPGTm-1 hybridizes with a total of about 40 to 50 kb of genomic DNA. Upon screening a Lambdagt11 cDNA library constructed with 3-methylcholanthrene-induced mRNA, some 60 transferase-positive clones were identified by immunoreactivity. At last one clone (2400 bp) shows enhanced (5- to 10-fold) hybridization to 3-methylcholanthrene-induced mRNA and, thus, appears to be regulated by the aromatic hydrocarbon (Ah) locus. A human transferase clone UDPGTh-1 (2500-bp), identified by hybridization to UDPGTm-1, hybridizes to a 2500-bp mRNA and hybridizes with about 22 kb of genomic DNA. The substrate specificity of UDPGTm-1 is being investigated in a yeast expression vector.
