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 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-alpha 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.
Yu
M
M
Key Laboratory of Genome Research, Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Second Medical University, Shanghai, 200025, People's Republic of China.
Tong
J H
JH
Mao
M
M
Kan
L X
LX
Liu
M M
MM
Sun
Y W
YW
Fu
G
G
Jing
Y K
YK
Yu
L
L
Lepaslier
D
D
Lanotte
M
M
Wang
Z Y
ZY
Chen
Z
Z
Waxman
S
S
Wang
Y X
YX
Tan
J Z
JZ
Chen
S J
SJ
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D003001:Cloning, Molecular; D016147:Genes, Tumor Suppressor; D006801:Humans; D007372:Interferons / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics*; D016415:Sequence Alignment; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C116468:IFIT3 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D014212:Tretinoin; D007372:Interferons