Mouse dioxin-inducible cytosolic aldehyde dehydrogenase-3: AHD4 cDNA sequence, genetic mapping, and differences in mRNA levels.
Mouse dioxin-inducible cytosolic aldehyde dehydrogenase-3: AHD4 cDNA sequence, genetic mapping, and differences in mRNA levels.
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小鼠二恶英诱导型胞质醛脱氢酶 3：AHD4 cDNA 序列、遗传图谱和 mRNA 水平差异。
DOI：
10.1097/00008571-199312000-00002
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Nebert,DW
中科院分区：
文献类型：
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作者：
Vasiliou,V;Reuter,SF;Kozak,CA;Nebert,DW
我们克隆了小鼠AHD 4 cDNA编码的'3类'胞质醛脱氢酶（ALDH-3c）。该cDNA全长1722 bp（不包括poly（A+）尾），5 '端非翻译区174 bp，3'端非翻译区186 bp。AHD 4编码453个氨基酸的蛋白质，包括第一个甲硫氨酸（M = 50 466）。鼠AHD-4蛋白分别与大鼠和人ALDH 3c蛋白91%和80%相似，与大鼠微粒体ALDH 3蛋白64%相同，与ALDH“1类”和“2类”蛋白< 28%相似。令人惊讶的是，与在细胞培养物和完整肝脏中表达的大鼠基因相反，鼠Ahd-4基因可由2、3、7、10、11、12、13、14、15、16、17、18、19细胞培养物中存在8-四氯二苯并对二恶英（TCDD;二恶英）或苯并芘，但完整成年或新生小鼠的肝脏中不存在。用全长cDNA探测的小鼠DNA的Southern杂交分析表明，Ahd-4基因可能跨度小于15 kb，并通过两个多位点杂交的分析被映射到Mgat-1和Shbg位点之间的染色体（Chr）11。在缺乏CYP 1A 1（芳烃羟化酶）活性的未经处理的小鼠肝癌Hepa-lclc 7突变系c37中以及在Chr 7上具有约1.2 cM纯合缺失的未经处理的14 CoS/14 CoS小鼠细胞系中，AHD 4 mRNA水平显着升高。我们的数据表明，Ahd-4基因在小鼠细胞培养物中的调节由三种不同的机制：Ah受体介导的诱导TCDD或苯并芘，CYP 1A 1代谢依赖性抑制，和Chr 7介导的推定的去抑制。
We have cloned and sequenced the murine AHD4 cDNA encoding the ‘Class 3’cytosolic aldehyde dehydrogenase (ALDH-3c). The cDNA is 1722 bp in length, excluding the poly (A+) tail, and has 5'and 3'nontranslated regions of 174bp and 186 bp, respectively. AHD4 encodes a protein of 453 amino acids, including the first methionine (M,= 50 466). The murine AHD4 protein is 91% and 80% similar to the rat and human ALDH3c proteins, respectively, 64% identical to the rat microsomal ALDH3 protein, and< 28% similar to ALDH ‘Class 1’and ‘Class 2’proteins, Surprisingly, in contrast to the rat gene that is expressed in both cell cultures and the intact liver, the murine Ahd-4 gene is inducible by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) or benzo ‘a’pyrene in cell cultures but not in liver of the intact adult or newborn mouse. Southern hybridization analysis of mouse DNA probed with the full-length cDNA reveals that the Ahd-4 gene is likely to span less than a total of 15 kb, and was mapped to chromosome (Chr) 11 between the Mgat-1 and Shbg loci by analysis of two multilocus crosses. AHD4 mRNA levels are strikingly elevated in the untreated mouse hepatoma Hepa-lclc7 mutant line c37 lacking CYP1A1 (aryl hydrocarbon hydroxylase) activity and in the untreated 14CoS/14CoS mouse cell line having a homozygous deletion of about 1.2 cM on Chr 7. Our data suggest that the Ahd-4 gene in murine cell cultures is regulated by three distinct mechanisms: Ah receptor-mediated induction by TCDD or benzo ‘a’pyrene, CYP1A1 metabolism-dependent repression, and Chr 7-mediated putative derepression.