TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue.
TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue.
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DOI：
10.1016/s0021-9258(18)98774-0
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发表时间：
1991-07
期刊：
影响因子：
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通讯作者：
D. Kujubu;B. Fletcher;B. Varnum;R. Lim;H. Herschman
中科院分区：
文献类型：
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作者：
D. Kujubu;B. Fletcher;B. Varnum;R. Lim;H. Herschman
TISlO是一种初级应答基因，其cDNA是由于其在Swiss 3 T3细胞中响应于12-0-十四酰基佛波醇-13-乙酸酯而快速、超诱导表达而克隆的。3.9-内切酶TISlO信息的5”非翻译区仅含有124个核苷酸，而3“非翻译区的长度几乎为2个内切酶。在这个长的3 '区域内，存在序列ATTTA的多个重复，该序列通常存在于快速降解的mRNA种类中。引物延伸揭示TISlO cDNA在TISlO基因的转录起始位点下游16个碱基对处开始。TISlO cDNA编码604个氨基酸的预测蛋白。计算机检索鉴定了预测的TISlO蛋白产物与鼠、羊和人前列腺素合酶/环氧合酶蛋白之间的惊人相似性。TISlO蛋白具有许多被认为对环氧合酶功能重要的相同保守氨基酸，TISlO mRNA在静止3 T3细胞中通过北方分析检测不到。在Swiss 3 T3细胞中，TISlO基因被毛喉素和血清以及12-0-十四酰基佛波醇-13-乙酸酯快速且瞬时诱导。这些药剂引起TISlO mRNA水平比环加氧酶mRNA水平显著得多的变化。TISlO基因的表达在培养的细胞系中似乎是高度细胞类型限制的;在超诱导条件下测试的12个细胞系中，仅啮齿动物胚胎Swiss 3 T3和Rat 1细胞系表达TISlO基因。
TISlO is a primary response gene whose cDNA was cloned as a result of its rapid, superinducible expression in Swiss 3T3 cells in response to 12-0-tetradecanoylphorbol-13-acetate. The 5” untranslated region of the 3.9-kilobase TISlO message contains only 124 nucleotides, whereas the 3 “untranslated region is almost 2 kilobases in length. Within this long 3’region, there are multiple repeats of the sequence ATTTA, a sequence often present in rapidly degraded mRNA species. Primer extension revealed that the TISlO cDNA begins 16 base pairs downstream of the transcription start site for the TISlO gene. The TISlO cDNA encodes a predicted protein of 604 amino acids. A computer search identified striking similarities between the predicted TISlO protein product and the murine, sheep, and human prostaglandin synthase/cyclooxygenase proteins. The TISlO protein has many of the same conserved amino acids that are thought to be important for cyclooxygenase function, TISlO mRNA is undetectable by Northern analysis in quiescent 3T3 cells. The TISlO gene is rapidly and transiently induced by forskolin and serum, as well as by 12-0-tetradecanoylphorbol-13-acetate, in Swiss 3T3 cells. These agents elicit far more dramatic changes in TISlO mRNA levels than in cyclooxygenase mRNA levels. The expression of the TISlO gene appears to be highly cell type-restricted in cultured cell lines; of 12 cell lines tested under superinducing conditions, only the rodent embryonic Swiss 3T3 and Rat1 cell lines expressed TIS 10 gene.