Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.109 (AST)
 6,066 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A complementary DNA (cDNA) for rat hepatic aryl sulfotransferase IV (AST IV) was isolated, characterized, and used as a hybridization probe to evaluate the molecular basis for the differential expression of AST IV during 2-acetylaminofluorine (2AAF)-induced hepatocarcinogensis. The AST IV cDNA clone was obtained by immunochemical screening of a male Sprague-Dawley rat liver cDNA library. The AST IV cDNA was found to be 1.3 kilobases long and to encode a fusion protein which was reactive with an antibody to AST IV and enzymatically able to generate the sulfuric acid ester of N-hydroxy-2AAF. Sequence analysis of the AST IV cDNA showed it to be 1127 residues in length and to have essentially complete homology with PST-I cDNA, a previously reported (S. Ozawa, et al., Nucleic Acids Res., 18: 4001, 1990), 1028-base cDNA for an uncharacterized rat liver aryl sulfotransferase. Comparison of the PST-I/AST IV cDNA-deduced amino acid sequence with data from a partial (51%) amino acid sequence analysis of purified AST IV showed complete amino acid homology, confirming the identity of the cDNA and establishing that AST IV was an N-blocked, 291-amino acid protein with a molecular mass of 33,909 daltons. The AST IV cDNA sequence differed from the PST-I cDNA in two principal ways: the 5' end lacked 18 coding bases, and the 3' end contained a 190-base extention in the untranslated region, including a consensus sequence for signalling polyadenylation. Studies of AST IV gene transcript levels showed that the livers of rats fed 2AAF for 3 wk (early stage hepatocarcinogenesis) and hyperplastic nodules from the livers of rats fed 2AAF for 19 wk (intermediate stage hepatocarcinogenesis) displayed transcript levels similar to those of livers from normal rats. This contrasted with the 60 to 70% lower than normal capacity of the mRNA fractions to express AST IV observed during in vitro translation. These results indicated that modulation of AST IV expression at early and intermediate stages of hepatocarcinogenesis involved regulatory mechanisms at the translational level. In contrast, mRNA fractions isolated from some 2AAF-induced liver tumors or from known chemical carcinogen-derived rat hepatoma cell lines showed losses of both AST IV transcript level and in vitro translation capacity, suggesting that regulation at the transcriptional level may become important at late stages of 2AAF-induced hepatocarcinogenesis. These results indicated that the molecular mechanisms for the 2AAF-mediated down regulation of AST IV expression during 2AAF-induced hepatocarcinogenesis involved alterations in regulation at both translational and transcriptional levels.
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PMID:Characterization of a complementary DNA for rat liver aryl sulfotransferase IV and use in evaluating the hepatic gene transcript levels of rats at various stages of 2-acetylaminofluorene-induced hepatocarcinogenesis. 151 41

Numerous studies have indicated that two classes of cytosolic STs are involved in the bioactivation of procarcinogens and drugs to reactive electrophiles, especially in rodent tissues. These two classes of STs are the hydroxysteroid STs, which are involved in the conjugation of hydroxymethyl PAHs, and the phenol STs involved in the sulfation of alkenylbenzenes and N-hydroxyarylamines. Purification studies of rat liver STs have clearly indicated that specific isoforms of hydroxysteroid and phenol STs are capable of sulfating procarcinogens in vitro. Rat liver STa and BAST I are structurally similar hydroxysteroid STs, which have been shown to sulfate and bioactive HMBA. Molecular cloning studies of the rat hydroxysteroid STs indicate that these enzymes are probably part of a family of closely related genes. The single human hydroxysteroid ST that has been characterized is very similar to the rat enzymes, but its role in the bioactivation of hydroxymethyl PAHs has not been established. Phenol STs have been demonstrated to have an important role in the bioactivation of alkenylbenzenes and N-hydroxyarylamines. Purification of rat phenol STs has identified several different forms, but only some appear to be involved in bioactivation of procarcinogens. Four isoforms (HAST I and II, AST III and IV) are apparently responsible for the majority of N-hydroxyarylamine sulfation. The relationship between these enzymes has not been established but they may represent similar enzymes. Different isoforms of rat phenol ST are also involved in the bioactivation of procarcinogens and drugs. However, the role of these phenol STs, PST-1, Mx-ST, and paracetamol ST, in carcinogenesis requires further study. In human tissues, only two phenol STs, P-PST and M-PST, have been identified. The role of these enzymes or unidentified STs in the sulfation of N-hydroxyarylamine procarcinogens has not yet been established. Initial reports of the molecular cloning and expression of the rat and human phenol ST genes will provide a valuable mechanism for the characterization of roles of the individual enzymes in bioactivation.
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PMID:Biochemistry of cytosolic sulfotransferases involved in bioactivation. 806 57

Phenol sulfotransferases catalyze the transfer of a sulfonate moiety from 3'-phosphoadenosyl 5'-phosphosulfate to a phenolic group of lipophylic substrates to generate soluble sulfate esters. Using a phenol sulfotransferase cDNA as probe to screen a human leukocyte genomic DNA library constructed in lambda EMBL3, we obtained a clone containing a complete gene sequence. Comparison of the gene sequence with that of the corresponding cDNAs, namely phenol-sulfating phenol sulfotransferase (P-PST) or thermostable sulfotransferase (TS-PST), and human aryl sulfotransferase 1 and 2 (HAST1 and HAST2) indicates that the gene possesses eight short exons separated by seven introns included in approximately 5 kb. HAST2 has a different 5' untranslated sequence, and thus is encoded by a different mRNA species. While the nucleotide sequence corresponding to the 5' noncoding region of P-PST (TS-PST and HAST1) is included in the exon I, the 5' untranslated sequence of HAST2 is located in the beginning of exon IIa. The remaining sequence in exon II that is identical to both P-PST and HAST2 was termed exon IIb. Exons III to VIII, which cover the coding region and the 3' untranslated region, are almost identical in all types of PST or AST cDNAs. These results suggest that the phenol sulfotransferase gene possesses two alternate promoters that drive the expression of the two different mRNA species in a tissue-specific manner. Transfection of chloramphenicol acetyl transferase (CAT) reporter gene vectors containing the 5'-flanking sequence upstream from exon I and exon II, respectively, in transformed human embryonal kidney (293) cells indicate that both sequences possess promoter activity with higher activity for promoter 1. RNA blot analysis indicates that human phenol sulfotransferase gene is expressed in kidney, liver, lung, leukocyte, colon, small intestine, and spleen.
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PMID:Human phenol sulfotransferase gene contains two alternative promoters: Structure and expression of the gene. 892 11