Differential expression of the UGT1A locus in human liver, biliary, and gastric tissue: Identification of UGT1A7 and UGT1A10 transcripts in extrahepatic tissue
Differential expression of the UGT1A locus in human liver, biliary, and gastric tissue: Identification of UGT1A7 and UGT1A10 transcripts in extrahepatic tissue
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DOI：
10.1124/mol.52.2.212
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发表时间：
1997-08-01
影响因子：
3.6
通讯作者：
Tukey, RH
中科院分区：
文献类型：
--
作者：
Strassburg, CP;Oldhafer, K;Tukey, RH
家族1 UDP-葡萄糖醛酸基转移酶（UGT）（UGT 1A）由预测至少9种单独蛋白质存在的基因座编码。通过外显子共享产生不同的蛋白质，这导致产生含有相同的245个氨基酸的羧基末端结构域和约280个氨基酸的氨基末端区域的蛋白质家族。UGT 1A基因座的多样性表明存在复杂的调控，最有可能是为了解释可变和特定的葡萄糖醛酸化要求。然而，组织特异性和肝外调控的完整UGT 1A基因座尚未确定的日期。在这项研究中，定量双链逆转录-聚合酶链反应被用来分析UGT 1A RNA表达在16个肝脏，4个胆道，和两个胃人体组织标本。发现UGT 1A 3和UGT 1A 6在三种组织中表达，而UGT 1A 5和UGT 1A 8不表达，肝细胞和胆道组织表达UGT 1A 1和UGT 1A 4，但肝细胞组织仅表达UGT 1A 9，而胆道组织表达UGT 1A 10。与肝细胞组织相反，胃组织除表达UGT 1A 10外还表达UGT 1A 7。UGT 1A 9在肝组织中、UGT 1A 7在胃组织中以及UGT 1A 10在胆道和胃组织中的表达为UGT 1A基因座在肝和肝外组织中的选择性调节提供了证据。克隆了新鉴定的UGT 1A 7和UGT 1A 10转录物，发现其具有95.86%的相同性。序列分析证实了两个蛋白的不同的285个氨基酸残基和相同的245个氨基酸残基的羧基末端。本研究为人类UGT 1A基因座的肝和肝外调节提供了证据，并确定了UGT 1A家族的两种新的肝外转录本。
Family 1 UDP-glucuronosyltransferases (UGTs) (UGT1A) are encoded by a locus that predicts the existence of at least nine individual proteins. The different proteins are generated by exon-sharing, which results in the production of a family of proteins that contain identical, 245-amino acid, carboxyl-terminal domains and an amino-terminal region of approximately 280 amino acids. The diversity of the UGT1A locus suggests the existence of complex regulation, most likely designed to account for the variable and specific glucuronidation requirements. However, the tissue-specific and extrahepatic regulation of the complete UGT1A locus has not been defined to date. In this study, quantitative duplex reverse transcription-polymerase chain reaction was used to analyze UGT1A RNA expression in 16 hepatic, four biliary, and two gastric human tissue specimens. UGT1A3 and UGT1A6 were found to be expressed in the three tissues, whereas UGT1A5 and UGT1A8 were not expressed, Hepatocellular and biliary tissue expressed UGT1A1 and UGT1A4 but hepatocellular tissue uniquely expressed UGT1A9, whereas biliary tissue expressed UGT1A10. In contrast to hepatocellular tissue, gastric tissue expressed UGT1A7 in addition to UGT1A10. The expression of UGT1A9 in hepatic tissue, UGT1A7 in gastric tissue, and UGT1A10 in biliary and gastric tissue provides evidence for the selective regulation of the UGT1A locus in hepatic and extrahepatic tissues. The newly identified UGT1A7 and UGT1A10 transcripts were cloned and found to be 95.86% identical. Sequence analysis confirmed two proteins with divergent amino termini of 285 residues and identical carboxyl termini of 245 residues. This study provides evidence for hepatic and extrahepatic regulation of the human UGT1A locus and identifies two novel extrahepatic transcripts of the UGT1A family.