[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.
Pan
Xiao-Rong
XR
Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Lou
Ye-Jiang
YJ
Zhang
Zhang-Lin
ZL
Xu
Gui-Ping
GP
Jia
Pei-Min
PM
Tong
Jian-Hua
JH
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