抗凋亡基因survivin细胞选择性表达的分子机制研究

We have successively expressed survivin protein in prokaryotic system. The purified recombinant protein was used to create monoclonal antibody by hybridomas. A HeLa cell line which expressed antisense RNA of survivin with the induction of 2mmol/L ZnCl2 has been constructed. Proliferation of HeLa cells was suppressed significantly after the expression of survivin has been inhibited. The inhibition also sensitized HeLa cells to chemothreapeutics and suppressed its cell cycle. We have also cloned the 5＇- and 3＇-flanking sequence of survivin genomic DNA by PCR. The core promoter which controlled the cell cycle expression of survivin was identified by nested mutation and reporter gene expression. It was interesting that inhibiting the expression of telomerase catalytic subunit (TERT) promoted the degradation of survivin protein by ubiquitin pathway. And co-inhibiting the expression of TERT and survivin would co-efficiently inhibited the proliferation of cancer cell. We first observed that normal proliferated peripheral lymphocyte activated by IL-2 and PHA-P in vitro expressed survivin. This suggested that survivin may play an important role in cell proliferation.

研究有肿瘤靶标意义的抗凋亡基因-survivin阻抑细胞凋亡分子途径的作用靶位；利用Matchmaker One-Hybrid System系统钓取survivin DNA特异性结合蛋白，探索survivin基因细胞≡裥员泶锏姆肿踊砗椭琢龇乐蔚男滦鸵┪锇斜攴肿拥纳杓凭哂兄匾睦砺塾肓俅惨庖濉