CLONING OF A GENE (RIG-G) ASSOCIATED WITH RETINOIC ACID-INDUCED DIFFERENTIATION OF ACUTE PROMYELOCYTIC LEUKEMIA-CELLS AND REPRESENTING A NEW MEMBER OF A FAMILY OF INTERFERON-STIMULATED GENES

In a cell line (NB4) derived from a patient with acute promyelocytic l eukemia, all-trans-retinoic acid (ATRA) and interferon (IFN) induce th e expression of a novel gene we call RIG-G (for retinoic acid-induced gene G). This gene codes for a 58-kDa protein containing 490 amino aci ds with several potential sites for post-translational modification. I n untreated NB4 cells, the expression of RIG-G is undetectable. ATRA t reatment induces the transcriptional expression of RIG-G relatively la te (12-24 hr) in a protein synthesis-dependent manner, whereas IFN-alp ha induces its expression early (30 min to 3 hr). Database search has revealed a high-level homology between RIG-G and several IFN-stimulate d genes in human (ISG54K, ISG56K, and IFN-inducible and retinoic acid- inducible 58K gene) and some other species, defining a well conserved gene family. The gene is composed of two exons and has been mapped by fluorescence in situ hybridization to chromosome 10q24, where two othe r human IFN-stimulated gene members are localized. A synergistic induc tion of RIG-G expression in NB4 cells by combined treatment with ATRA and IFNs suggests that a collaboration exists between their respective signaling pathways.