Isolation and expression of a cDNA encoding a male-specific rat sulfotransferase that catalyzes activation of N-hydroxy-2-acetylaminofluorene.
A cDNA (ST1C1 cDNA) encoding a N-hydroxyarylamine sulfotransferase (HAST-I) was isolated from a liver cDNA library of a male adult rat and was expressed in COS-1 cells. ST1C1 cDNA (1363 base pairs) encoded a protein of 304 amino acids with a molecular mass of 35,768 daltons, which shared 50.7 and 46.1% sequence identity with rat aryl (ST1A1 (PST-1)) and estrogen (rOST) sulfotransferases, respectively. N-terminal amino acid sequences of three digested polypeptide fragments of HAST-I were completely identical with two portions of the ST1C1 amino acid sequence. The profile of age- and sex-related expression of ST1C1 mRNA was quite consistent with changes in the sulfating activity of N-hydroxyarylamine and HAST contents in rat livers. ST1C1 expressed in COS-1 cells catalyzed a sulfation of N-hydroxy-2-acetylaminofluorene (N-OH-AAF) at a rate of 4.98 nmol/mg of protein/min and mediated PAPS (3'-phosphoadenosine-5'-phosphosulfate)-dependent DNA binding of N-OH-AAF. Although ASTIV was believed to be responsible for the activation of N-OH-AAF, ST1A1 encoding an arylsulfotransferase ASTIV, showed only a marginal activity in a sulfation and covalent binding of N-OH-AAF. These data clearly indicate that ST1C1 cDNA codes a new form of a male-dominant sulfotransferase (HAST) responsible for the bioactivation of N-hydroxyarylamines in rat livers.
Nagata
K
K
Department of Pharmacology, School of Medicine, Keio University, Tokyo, Japan.
Ozawa
S
S
Miyata
M
M
Shimada
M
M
Gong
D W
DW
Yamazoe
Y
Y
Kato
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001711:Biotransformation; D015153:Blotting, Western; D002384:Catalysis; D002417:Cattle; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary; D006881:Hydroxyacetylaminofluorene / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015238:Sulfotransferases / Q000235:genetics* / Q000378:metabolism
D018076:DNA, Complementary; D012333:RNA, Messenger; D006881:Hydroxyacetylaminofluorene; D004247:DNA; C084221:St1C1 N-hydroxyarylamine sulfotransferase; D015238:Sulfotransferases