Characterization of monoclonal antibodies against GRIM-19, a novel IFN-beta and retinoic acid-activated regulator of cell death.
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.
Hu
Jiadi
J
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.
Angell
Jon E
JE
Zhang
Jun
J
Ma
Xinrong
X
Seo
Taegun
T
Raha
Abhijit
A
Hayashi
Jun
J
Choe
Joonho
J
Kalvakolanu
Dhananjaya V
DV
D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D005786:Gene Expression Regulation / Q000187:drug effects*; D016147:Genes, Tumor Suppressor; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology*; D051379:Mice; D008817:Mice, Mutant Strains; D009247:NADH, NADPH Oxidoreductases / Q000276:immunology* / Q000378:metabolism; D009687:Nuclear Proteins / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D051017:Apoptosis Regulatory Proteins; D007155:Immunologic Factors; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D014212:Tretinoin; D016899:Interferon-beta; D009247:NADH, NADPH Oxidoreductases; C486684:Grim19 protein, mouse; C439057:NDUFA13 protein, human