Disease relevance of NDUFA13

• A proteomic analysis reveals the loss of expression of the cell death regulatory gene GRIM-19 in human renal cell carcinomas [1].
• GRIM-19 expression is decreased in inflamed mucosa of patients with inflammatory bowel diseases [2].
• Viral interferon regulatory factor 1 of Kaposi's sarcoma-associated herpesvirus interacts with a cell death regulator, GRIM19, and inhibits interferon/retinoic acid-induced cell death [3].
• Somatic missense mutations in GRIM-19 were detected in three of 20 sporadic Hurthle cell carcinomas [4].
• In one of the sporadic Hurthle cell papillary carcinomas positive for GRIM-19 mutation, we have also detected a ret/PTC-1 rearrangement [4].

High impact information on NDUFA13

• The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3 [5].
• Mutational analysis indicates that the transactivation domain of STAT3, especially residue S727, is required for GRIM-19 binding [5].
• We reexamined the cellular localization of GRIM-19 in various cell types and found its primary localization in the mitochondria [6].
• GRIM-19 was originally identified as a nuclear protein with apoptotic nature in interferon (IFN)- and all-trans-retinoic acid (RA)-induced tumor cells [6].
• Our result demonstrates that GRIM-19, a gene product with a specific role in IFN-RA-induced cell death, is a functional component of mitochondrial complex I and is essential for early embryonic development [6].

Biological context of NDUFA13

• Using an RCC cell line, we show that down regulation of GRIM-19 promotes tumor growth via an augmentation of STAT3-dependent gene expression [1].
• The vIRF1 protein deregulates GRIM19-induced apoptosis in the presence of IFN/all-trans-retinoic acid (RA) and inhibits IFN/RA-induced cell death [3].
• Here, we describe the localization of GRIM-19 to human chromosome 19p13 [7].
• Furthermore, GRIM-19 is detected in the native form of mitochondrial complex I. Finally, we show that elimination of GRIM-19 destroys the assembly and electron transfer activity of complex I and also influences the other complexes in the mitochondrial respiratory chain [6].
• Point mutation in GRIM-19: a new genetic lesion in Hurthle cell thyroid carcinomas [8].

Anatomical context of NDUFA13

• GRIM-19 also controls pathogen invasion of intestinal epithelial cells [2].
• We demonstrate that GRIM-19, a protein with homology to the NADPH dehydrogenase complex, interacts with endogenous NOD2 in HT29 cells [2].
• 5. GRIM-19(-/-) blastocysts show retarded growth in vitro and, strikingly, display abnormal mitochondrial structure, morphology, and cellular distribution [6].
• We have searched for GRIM-19 mutations in a series of 52 thyroid tumours [4].

Associations of NDUFA13 with chemical compounds

• Antisense ablation of GRIM-19 caused resistance to cell death induced by IFN plus retinoic acid and conferred a growth advantage to cells [5].
• GRIM-19 is required for NF-kappaB activation following NOD2-mediated recognition of bacterial muramyl dipeptide [2].
• Knockdown of GRIM-19 (gene associated with retinoid-interferon-induced mortality-19) and NDUFS3 (NADH dehydrogenase (ubiquinone) Fe-S protein 3), two subunits of MRC complex I, by siRNA in two cancer cell lines conferred resistance to IFN-beta/RA-induced apoptosis and reduced ROS production [9].

Physical interactions of NDUFA13

• Induction of olfactomedin 4 (OLFM4(GW112/hGC-1)) in cancer cells was recently reported to have a novel antiapoptotic action via binding to the potent apoptosis inducer GRIM-19 [10].

Regulatory relationships of NDUFA13

• 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 [11].

Other interactions of NDUFA13

• GRIM-19 may be a key component in NOD2-mediated innate mucosal responses and serve to regulate intestinal epithelial cell responses to microbes [2].
• Chromosomal localization of human GRIM-19, a novel IFN-beta and retinoic acid-activated regulator of cell death [7].
• 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 [11].
• We show here that GW112 is associated with GRIM-19, a protein known to be involved in regulating cellular apoptosis [12].
• A recently discovered gene, GRIM-19 has been found to fulfil two roles within the cell: as a member of the interferon-beta and retinoic acid-induced pathway of cell death, and as part of the mitochondrial Complex I assembly [4].

Analytical, diagnostic and therapeutic context of NDUFA13

• Using the yeast two-hybrid assay, we identified genes associated with retinoid-IFN-induced mortality-19 (GRIM19), which interacts directly with vIRF1, both in vivo and in vitro [3].
• To reveal its biological role, we generated mice deficient in GRIM-19 by gene targeting [6].

References