Patriotis C, Makris A, Bear S E, Tsichlis P N
Fox Chase Cancer Center, Philadelphia, PA 19111.
Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2251-5. doi: 10.1073/pnas.90.6.2251.
The Tpl-2 locus, cloned by provirus tagging from one of three sublines of the Moloney leukemia virus-induced rat thymoma 2769, defines a gene encoding a protein kinase associated with progression in 22.5% of the tumors. Tpl-2 is expressed primarily in spleen, thymus, liver, and lung. Provirus integration occurs in the last intron of the gene, leading to the expression of a truncated mRNA that terminates in the proviral long terminal repeat and encodes a protein with an altered C-terminal domain. Strong evidence that this genetic change confers growth advantage to affected cell clones was provided by the finding that, during cultivation of all three sublines derived from tumor 2769, cells were selected that harbored independent provirus insertions in the Tpl-2 locus. Exposure of normal rat spleen cells to Con A induces the expression of enhanced levels of Tpl-2 within the first 60 min from the time of exposure suggesting that, in normal splenocytes, Tpl-2 may be involved in the transition from a quiescent to the G1 phase of the cell cycle.
通过从莫洛尼白血病病毒诱导的大鼠胸腺瘤2769的三个亚系之一中进行前病毒标签克隆得到的Tpl-2基因座，定义了一个编码蛋白激酶的基因，该蛋白激酶在22.5%的肿瘤进展中起作用。Tpl-2主要在脾脏、胸腺、肝脏和肺中表达。前病毒整合发生在该基因的最后一个内含子中，导致截短的mRNA表达，该mRNA在病毒前长末端重复序列处终止，并编码一个C末端结构域改变的蛋白质。在源自肿瘤2769的所有三个亚系的培养过程中，发现了在Tpl-2基因座中携带独立前病毒插入的细胞，这一发现为这种基因变化赋予受影响细胞克隆生长优势提供了有力证据。正常大鼠脾细胞暴露于刀豆球蛋白A后，在暴露后的前6小时内诱导Tpl-2表达水平升高，这表明在正常脾细胞中，Tpl-2可能参与细胞周期从静止期到G1期的转变。
