Kanamori H, Suzuki N, Siomi H, Nosaka T, Sato A, Sabe H, Hatanaka M, Honjo T
Department of Medical Chemistry, Kyoto University Faculty of Medicine, Japan.
EMBO J. 1990 Dec;9(12):4161-6. doi: 10.1002/j.1460-2075.1990.tb07639.x.
Expression of the pX gene products (p40tax, p27rex and p21X-III) of human T cell leukemia virus type 1 (HTLV-1), which is known to be a causative agent of adult T cell lymphoma/leukemia, induces expression of the interleukin-2 receptor alpha chain (IL-2R alpha) on infected T cells. Comparison of IL-2R alpha promoter activities has revealed that the transcriptional activation of the promoter alone cannot explain the large numbers of IL-2R alpha expressed on HTLV-1 infected cells. We found that the rates of the IL-2R alpha mRNA degradation were greatly reduced in pX-positive cells as compared with pX-negative cells. Simultaneous transfection of the expression vector plasmid containing IL-2R alpha cDNA and similar plasmids containing various pX sequences showed that p27rex elongated the half life of IL-2R alpha mRNA. As p27rex did not affect the transport of the IL-2R alpha mRNA from nucleus to cytoplasm, prolongation of the IL-2R alpha mRNA half life by p27rex is ascribed to stabilization of the mRNA. Experiments using deletion mutants and chimeric constructs of the IL-2R alpha cDNA demonstrated that the coding sequence but not the 5' or 3' untranslated region of the IL-2R alpha mRNA sequence is responsible for its protection by p27rex.
已知人类T细胞白血病病毒1型(HTLV-1)是成人T细胞淋巴瘤/白血病的病原体,其pX基因产物(p40tax、p27rex和p21X-III)的表达可诱导受感染T细胞上白细胞介素-2受体α链(IL-2Rα)的表达。对IL-2Rα启动子活性的比较表明,仅启动子的转录激活无法解释HTLV-1感染细胞上大量表达的IL-2Rα。我们发现,与pX阴性细胞相比,pX阳性细胞中IL-2Rα mRNA的降解速率大大降低。同时转染含有IL-2Rα cDNA的表达载体质粒和含有各种pX序列的类似质粒表明,p27rex延长了IL-2Rα mRNA的半衰期。由于p27rex不影响IL-2Rα mRNA从细胞核到细胞质的转运,因此p27rex对IL-2Rα mRNA半衰期的延长归因于mRNA的稳定。使用IL-2Rα cDNA的缺失突变体和嵌合构建体进行的实验表明,IL-2Rα mRNA序列的编码序列而非5'或3'非翻译区负责其受p27rex的保护。