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

• Published in: Proceedings of the National Academy of Sciences - PNAS 1997-07, Vol.94 (14), p.7406-7411
• Main Authors: Yu, Man, Tong, Jian-Hua, Mao Mao, Kan, Li-Xin, Liu, Meng-Min, Sun, Yi-Wu, Fu, Gang, Jing, Yong-Kui, Yu, Long, Lepaslier, Denis, Lanotte, Michel, Wang, Zhen-Yi, Chen, Zhu, Waxman, Samuel, Wang, Ya-Xin, Tan, Jia-Zhen, Chen, Sai-Juan
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Antineoplastic Agents - pharmacology; Base Sequence; Biological Sciences; Cell Differentiation - drug effects; Cell Differentiation - genetics; Cell lines; Cellular differentiation; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 10; Cloning; Cloning, Molecular; Complementary DNA; Exons; Generally accepted auditing standards; Genes; Genes, Tumor Suppressor; Genetics; Humans; Interferon; Interferons - genetics; Intracellular Signaling Peptides and Proteins; Leukemia; Leukemia, Promyelocytic, Acute - genetics; Leukemia, Promyelocytic, Acute - pathology; Messenger RNA; Molecular Sequence Data; Phosphorylation; Proteins - genetics; Sequence Alignment; Tretinoin - pharmacology; Tumor Cells, Cultured
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.94.14.7406

In a cell line (NB4) derived from a patient with acute promyelocytic leukemia, all-trans-retinoic acid (ATRA) and interferon (IFN) induce the 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 acids with several potential sites for post-translational modification. In untreated NB4 cells, the expression of RIG-G is undetectable. ATRA treatment induces the transcriptional expression of RIG-G relatively late (12-24 hr) in a protein synthesis-dependent manner, whereas IFN-α induces its expression early (30 min to 3 hr). Database search has revealed a high-level homology between RIG-G and several IFN-stimulated 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 other human IFN-stimulated gene members are localized. A synergistic induction of RIG-G expression in NB4 cells by combined treatment with ATRA and IFNs suggests that a collaboration exists between their respective signaling pathways.