Article

Identification of GRIM-19, a novel cell death-regulatory gene induced by the interferon-beta and retinoic acid combination, using a genetic approach.

Greenebaum Cancer Center, Department of Microbiology and Immunology, Molecular and Cellular Biology Program, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Journal of Biological Chemistry (impact factor: 4.77). 11/2000; 275(43):33416-26. DOI:10.1074/jbc.M003929200 pp.33416-26
Source: PubMed

ABSTRACT We show here that the combination of interferon-beta (IFN-beta) and all-trans-retinoic acid (RA) induces the death of tumor cells. To understand the molecular basis for synergistic growth-suppressive action and to identify the gene products that participate in this process, we have employed an antisense knock-out technique. This approach permits the isolation of cell death-associated genes based on their selective inactivation by overexpression of antisense cDNAs. Because the antisense mRNA inactivates gene expression of death-specific genes, transfected cells survive in the presence death inducers. Several Genes associated with Retinoid-IFN-induced Mortality (GRIM) were identified using this approach. Here we report the isolation of a novel GRIM gene, GRIM-19. This 552-base pair cDNA encodes a 16-kDa protein. Antisense expression of GRIM-19 confers a strong resistance against IFN/RA-induced death by reducing the intracellular levels of GRIM-19 protein. Overexpression of GRIM-19 enhances cell death in response to IFN/RA. GRIM-19 is primarily a nuclear protein whose expression is induced by the IFN/RA combination. Together, our studies identify a novel cell death-regulatory molecule.

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Keywords

552-base pair cDNA encodes
 
all-trans-retinoic acid
 
antisense knock-out technique
 
approach permits
 
cell death-associated genes
 
death-specific genes
 
gene products
 
GRIM-19 enhances cell death
 
GRIM-19 protein
 
IFN/RA combination
 
IFN/RA-induced death
 
intracellular levels
 
molecular basis
 
novel cell death-regulatory molecule
 
novel GRIM gene
 
presence death inducers
 
Retinoid-IFN-induced Mortality
 
selective inactivation
 
synergistic growth-suppressive action
 
tumor cells