Molecular mechainism of apotosis induced by a novel RNA binding protein D8

我们发现并鉴定了一个新的基因D8，它参与了细胞凋亡的诱导，并获得了以下结果：1)D8在肿瘤细胞系如HepG2中过表达导致细胞凋亡的诱导。RNAi敲低实验显示，p53和TGF-β介导的细胞凋亡诱导需要D8。2)用抗癌试剂如5FU、阿霉素处理细胞可诱导D8表达。敲低D8抑制5fu和阿霉素诱导的细胞凋亡。3)发现Bim是BH3蛋白家族的成员，与D8的KH结构域结合。RNAi敲低实验表明，Bim在D8介导的细胞凋亡中起重要作用，D8可以稳定Bim mRNA。5)为了产生D8敲低小鼠，我们建立了缺乏D8基因的ES细胞系。我们发现D8有三个家族成员。

We identified and characterized a novel gene termed D8 that is involved in the induction of apoptosis and obtained the following results :1)Overexpression of D8 in tumor cell lines such as HepG2 resulted in the induction of apoptosis. Knockdown experiments using RNAi revealed that D8 is required for p53 and TGF-β-mediated induction of apoptosis2)Treatment of cells with anticancer reagents such as 5FU and adriamycin resulted in the induction of D8 expression. Knockdown of D8 inhibited 5FU-and adriamycin-induced apoptosis.3)Bim, a family member of the BH3 only family of proteins, was found to bind to the KH domain of D8. Knockdown experiments using RNAi revealed that Bim is important for D8-mediated apoptosis4)D8 was found to stabilize the Bim mRNA.5)To generate D8 knockdown mice, we established ES cell lines lacking the D8 gene.6)We found that D8 possesses three family members.