Adenosine deaminase messenger RNAs in lymphoblast cell lines derived from leukemic patients and patients with hereditary adenosine deaminase deficiency.
Adenosine deaminase messenger RNAs in lymphoblast cell lines derived from leukemic patients and patients with hereditary adenosine deaminase deficiency.
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来自白血病患者和遗传性腺苷脱氨酶缺乏症患者的淋巴母细胞系中的腺苷脱氨酶信使 RNA。
DOI：
10.1172/jci110920
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发表时间：
1983
期刊：
影响因子：
--
通讯作者：
Hutton,JJ
中科院分区：
文献类型：
--
作者：
Adrian,GS;Hutton,JJ
遗传性腺苷脱氨酶 (ADA) 缺乏通常会导致严重的淋巴细胞减少症并伴有严重的联合免疫缺陷病。 ADA 缺陷患者的细胞中 ADA 催化活性和 ADA 蛋白的含量低于正常水平，有时甚至无法检测到。目前对导致遗传性 ADA 缺陷的分子缺陷知之甚少。 ADA 信使 RNA 及其翻译产物在以下七种人淋巴母细胞系中进行了表征：来自正常成人的 GM-130、GM-131 和 GM-2184； GM-3043，来自 ADA 部分缺陷、免疫功能正常的！Kung 部落成员； GM-2606 来自 ADA 缺陷、免疫缺陷儿童；来自白血病儿童的 CCRF-CEM 和 HPB-ALL。 ADA 信使 (m)RNA 存在于所有品系中并且是聚腺苷酸化的。通过体外翻译每个细胞系的 mRNA 合成的 ADA 与正常人 ADA 的抗血清反应，并且具有正常的分子大小。没有证据表明 ADA 的翻译后加工发生在正常、白血病或突变的淋巴母细胞系中。三种正常细胞系和两种白血病细胞系提取物中特定可翻译 mRNA 的相对水平与 ADA 蛋白水平平行。然而，在突变体 GM-2606 和 GM-3043 系中发现了出人意料的高水平 ADA 特异性、可翻译 mRNA，相当于三个正常系的三到四倍。 ADA mRNA 量和 ADA 合成速率的差异似乎对于维持具有正常 ADA 的淋巴母细胞系之间 ADA 水平的差异至关重要。至少两种突变细胞系中的 ADA 缺陷不是由可翻译 mRNA 水平不足引起的，除非该 mRNA 存在某种翻译控制，否则特征性细胞 ADA 缺陷很可能继发于有缺陷的 ADA 蛋白的合成和快速降解。
Hereditary deficiency of adenosine deaminase (ADA) usually causes profound lymphopenia with severe combined immunodeficiency disease. Cells from patients with ADA deficiency contain less than normal, and sometimes undetectable, amounts of ADA catalytic activity and ADA protein. The molecular defects responsible for hereditary ADA deficiency are poorly understood. ADA messenger RNAs and their translation products have been characterized in seven human lymphoblast cell lines derived as follows: GM-130, GM-131, and GM-2184 from normal adults; GM-3043 from a partially ADA deficient, immunocompetent !Kung tribesman; GM-2606 from an ADA deficient, immunodeficient child; CCRF-CEM and HPB-ALL from leukemic children. ADA messenger (m)RNA was present in all lines and was polyadenylated. The ADA synthesized by in vitro translation of mRNA from each line reacted with antisera to normal human ADA and was of normal molecular size. There was no evidence that posttranslational processing of ADA occurred in normal, leukemic, or mutant lymphoblast lines. Relative levels of specific translatable mRNA paralleled levels of ADA protein in extracts of the three normal and two leukemic lines. However, unexpectedly high levels of ADA specific, translatable mRNA were found in the mutant GM-2606 and GM-3043 lines, amounting to three to four times those of the three normal lines. Differences in the amounts of ADA mRNA and rates of ADA synthesis appear to be of primary importance in maintaining the differences in ADA levels among lymphoblast lines with structurally normal ADA. ADA deficiency in at least two mutant cell lines is not caused by deficient levels of translatable mRNA, and unless there is some translational control of this mRNA, the characteristic cellular ADA deficiency is most likely secondary to synthesis and rapid degradation of a defective ADA protein.Images