Máximo Valdemar, Lima Jorge, Soares Paula, Silva André, Bento Inês, Sobrinho-Simões Manuel
Institute of Molecular Pathology and Immunology of the University of Porto, Rua Dr. Roberto Frias s/n, Porto, Portugal.
Adv Anat Pathol. 2008 Jan;15(1):46-53. doi: 10.1097/PAP.0b013e31815e5258.
GRIM-19, a gene associated with retinoid interferon-induced mortality, was originally identified as a critical regulatory protein for interferon-beta and retinoic acid-induced cell death. It was also demonstrated that GRIM-19 is involved in mitochondrial metabolism, as an integrant component of complex I of the mitochondrial respiratory chain. GRIM-19 appears, therefore, as a dual function protein involved in cell death and mitochondrial metabolism. GRIM-19 knock out leads to Complex I assembly disruption and embryonic lethality in mice, showing that it is a crucial component of the mitochondrial respiratory chain essential for early embryonic development. Recently, mutations in GRIM-19 were described in Hürthle cell (mitochondrion-rich) tumors of the thyroid and down-regulation or loss of its expression were found in renal cell carcinomas, suggesting a role for GRIM-19 in tumorigenesis. As GRIM-19 binds and inhibits the signal transducer and activator of transcription-3 (STAT3), which has been shown to be activated in several human tumors it is tempting to advance that GRIM-19 may function as a tumor suppressor gene in tumors in which STAT3 plays a major role.
GRIM-19是一种与类视黄醇干扰素诱导的细胞死亡相关的基因，最初被鉴定为干扰素-β和视黄酸诱导的细胞死亡的关键调节蛋白。研究还表明，GRIM-19作为线粒体呼吸链复合体I的一个组成成分，参与线粒体代谢。因此，GRIM-19似乎是一种具有双重功能的蛋白，参与细胞死亡和线粒体代谢。GRIM-19基因敲除会导致小鼠复合体I组装破坏和胚胎致死，表明它是早期胚胎发育所必需的线粒体呼吸链的关键组成部分。最近，在甲状腺Hurthle细胞（富含线粒体）肿瘤中发现了GRIM-19的突变，并且在肾细胞癌中发现其表达下调或缺失，提示GRIM-19在肿瘤发生中发挥作用。由于GRIM-19能结合并抑制信号转导和转录激活因子3（STAT3），而STAT3在多种人类肿瘤中已被证明处于激活状态，因此很容易推测GRIM-19在STAT3起主要作用的肿瘤中可能作为肿瘤抑制基因发挥作用。
