[Regulation mechanism for rig-g gene expression induced by all-trans retinoic acid].
To investigate the molecular mechanisms of all-trans retinoic acid (ATRA)-induced rig-g gene expression and to better understand the signal transduction of ATRA during acute promyelocytic leukemia (APL) cell differentiation, the luciferase reporter assay, co-immunoprecipitation and chromatin immunoprecipitation were used to clarify the basic transcriptional factors, which directly initiated the expression of rig-g gene. The results showed that the expression of STAT2, IRF-9 and IRF-1 could be upregulated by ATRA with different kinetics in NB4 cells. IRF-9 was able to interact with STAT2 to form a complex, which could bind the rig-g gene promoter and trigger the rig-g expression. IRF-1 alone could also activate the reporter gene containing rig-g gene promoter, but C/EBPalpha could strongly inhibit this transcription activity of IRF-1. It is concluded that during ATRA-induced APL cell differentiation, IRF-1 is first upregulated by ATRA, and then IRF-1 increases the protein levels of IRF-9 and STAT2 with the downregulation of C/EBPalpha. The complex of IRF-9 and STAT2 is the primary transcriptional factor for rig-g gene induction. This study will be helpful for better understanding the signal transduction networks of ATRA during the course of APL cell differentiation.
Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Xiao-Rong
XR
Pan
Ye-Jiang
YJ
Lou
Zhang-Lin
ZL
Zhang
Gui-Ping
GP
Xu
Pei-Min
PM
Jia
Jian-Hua
JH
Tong
D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D005809:Genes, Regulator / Q000187:drug effects*; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D050795:STAT2 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D022763:CCAAT-Enhancer-Binding Protein-alpha; C116468:IFIT3 protein, human; C494257:IRF1 protein, human; C494227:IRF9 protein, human; D050856:Interferon Regulatory Factor-1; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D047908:Intracellular Signaling Peptides and Proteins; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D014212:Tretinoin