Identification of GRIM-19, a novel cell death-regulatory gene induced by the interferon-β and retinoic acid combination, using a genetic approach
Identification of GRIM-19, a novel cell death-regulatory gene induced by the interferon-β and retinoic acid combination, using a genetic approach
复制标题
DOI：
10.1074/jbc.m003929200
复制
发表时间：
2000-10-27
影响因子：
4.8
通讯作者：
Kalvakolanu, DV
中科院分区：
文献类型：
--
作者：
Angell, JE;Lindner, DJ;Kalvakolanu, DV
我们在这里表明，干扰素-β（TFN-β）和全反式维甲酸（RA）的组合诱导肿瘤细胞的死亡。为了了解协同生长抑制作用的分子基础，并确定参与这一过程的基因产物，我采用了反义基因敲除技术。这种方法允许基于通过反义cDNA的过表达而选择性失活的细胞死亡相关基因的分离。因为反义mRNA使死亡特异性基因的基因表达失活，所以转染的细胞在死亡诱导物存在下存活。使用这种方法鉴定了与类维生素A-IFN-诱导的死亡率（GRIM）相关的几个基因。在这里，我报告，一个新的GRIM基因，GRIM-19的分离。该552个碱基对的cDNA编码16-kDa的蛋白。GRIM-19的反义表达通过降低GRIM-19蛋白的细胞内水平而赋予对IFN/RA诱导的死亡的强抗性。GRIM-19的过表达增强响应于IFN/RA的细胞死亡。GRIM-IS主要是一种核蛋白，其表达由IFN/RA组合诱导。总之，我们的研究确定了一种新的细胞死亡调节分子。
We show here that the combination of interferon-beta (TFN-beta) and all-trans-retinoic acid (RA) induces the death of tumor cells. To understand the molecular basis for synergistic growth-suppressive action and to identify the gene products that participate in this process, me have employed an antisense knock-out technique. This approach permits the isolation of cell death-associated genes based on their selective inactivation by over-expression of antisense cDNAs, Because the antisense mRNA inactivates gene expression of death-specific genes, transfected cells survive in the presence death inducers. Several Genes associated with Retinoid-IFN-induced Mortality (GRIM) were identified using this approach. Here me report, the isolation of a novel GRIM gene, GRIM-19. This 552-base pair cDNA encodes a 16-kDa protein. Antisense expression of GRIM-19 confers a strong resistance against IFN/RA-induced death by reducing the intracellular levels of GRIM-19 protein. Overexpression of GRIM-19 enhances cell death in response to IFN/RA. GRIM-IS is primarily a nuclear protein whose expression is induced by the IFN/RA combination. Together, our studies identify a novel cell death-regulatory molecule.