Kissil J L, Kimchi A
Mol Med Today. 1998 Jun;4(6):268-74. doi: 10.1016/s1357-4310(98)01263-5.
Aberrations of apoptosis are implicated in many diseases, including cancer, autoimmune disease, cardiovascular disease and neurodegeneration. The cell's apoptotic machinery is, therefore, an important potential target for the development of new therapies. Our laboratory has used a strategy called technical knockout (TKO) to identify novel genes involved in apoptosis. TKO is based on random inactivation of gene expression with antisense cDNA libraries, followed by selection of those cells that survive in the continuous presence of an apoptotic stimulus. Using this approach, we have isolated five novel genes, including a serine/threonine kinase, a nucleotide-binding protein and a homologue of the p220 translation initiation factor. Expression of one of these genes (DAP kinase) is lost in some cancers, and this loss appears to increase the metastatic potential of some tumours.
细胞凋亡异常与许多疾病有关，包括癌症、自身免疫性疾病、心血管疾病和神经退行性变。因此，细胞的凋亡机制是开发新疗法的一个重要潜在靶点。我们实验室采用了一种称为技术敲除（TKO）的策略来鉴定参与细胞凋亡的新基因。TKO基于用反义cDNA文库随机灭活基因表达，然后选择在凋亡刺激持续存在下存活的细胞。使用这种方法，我们分离出了五个新基因，包括一个丝氨酸/苏氨酸激酶、一个核苷酸结合蛋白和p220翻译起始因子的一个同源物。这些基因之一（DAP激酶）的表达在某些癌症中缺失，这种缺失似乎增加了一些肿瘤的转移潜能。
