Hu Jiadi, Angell Jon E, Zhang Jun, Ma Xinrong, Seo Taegun, Raha Abhijit, Hayashi Jun, Choe Joonho, Kalvakolanu Dhananjaya V
Marlene and Stewart Greenebaum Cancer Center, Department of Microbiology and Immunology, Molecular and Cellular Biology Program, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
J Interferon Cytokine Res. 2002 Oct;22(10):1017-26. doi: 10.1089/107999002760624242.
A combination of interferon-beta (IFN-beta) and all-trans retinoic acid (IFN/RA) induces tumor cell apoptosis via some unknown mechanisms. Apoptosis is a gene-directed process that limits the proliferation of undesired cells. Several genes are required to regulate cell death in the higher-order animals. Earlier, we employed a gene expression knockout technique to isolate cell death-related genes. A novel gene, the gene associated with retinoid-interferon-induced mortality-19 (GRIM-19), was found to be essential for tumor cell death induced by IFN/RA. Here, we describe the development and characterization of three monoclonal antibodies (mAbs) against GRIM-19. GRIM-19 is present in the nucleus and cytoplasm. Its expression is induced by the IFN/RA combination. We also show that GRIM-19 inhibits the cell-transforming property of viral oncogenic protein viral IFN regulatory factor-1 (vIRF-1) via a physical interaction. mAbs developed in this study should be useful for studying the other physiologic roles of GRIM-19 and serve as a potent tool for studying tumor responses to IFN/RA therapy.
干扰素-β（IFN-β）和全反式维甲酸（IFN/RA）联合使用可通过一些未知机制诱导肿瘤细胞凋亡。凋亡是一个由基因指导的过程，可限制不需要的细胞增殖。在高等动物中，需要几个基因来调节细胞死亡。此前，我们采用基因表达敲除技术来分离与细胞死亡相关的基因。发现一个新基因，即类视黄醇-干扰素诱导死亡率-19相关基因（GRIM-19），对IFN/RA诱导的肿瘤细胞死亡至关重要。在此，我们描述了三种抗GRIM-19单克隆抗体（mAb）的研制及特性。GRIM-19存在于细胞核和细胞质中。其表达由IFN/RA联合诱导。我们还表明，GRIM-19通过物理相互作用抑制病毒致癌蛋白病毒干扰素调节因子-1（vIRF-1）的细胞转化特性。本研究中研制的单克隆抗体对于研究GRIM-19的其他生理作用应是有用的，并可作为研究肿瘤对IFN/RA治疗反应的有力工具。
