Characterization of monoclonal antibodies against GRIM-19, a novel IFN-beta and retinoic acid-activated regulator of cell death

J Interferon Cytokine Res. 2002 Oct;22(10):1017-26. doi: 10.1089/107999002760624242.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Antibodies, Monoclonal / immunology*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins
  • Gene Expression Regulation / drug effects*
  • Genes, Tumor Suppressor*
  • Humans
  • Immunologic Factors / pharmacology
  • Interferon-beta / pharmacology*
  • Mice
  • Mice, Mutant Strains
  • NADH, NADPH Oxidoreductases / immunology*
  • NADH, NADPH Oxidoreductases / metabolism
  • Nuclear Proteins / immunology
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism
  • Tretinoin / pharmacology
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Apoptosis Regulatory Proteins
  • Immunologic Factors
  • Nuclear Proteins
  • Recombinant Proteins
  • Tretinoin
  • Interferon-beta
  • NADH, NADPH Oxidoreductases
  • GRIM19 protein, human
  • Grim19 protein, mouse