Regulation mechanism for rig-g gene expression induced by all-trans retinoic acid.
- Author:
Xiao-Rong PAN
1
;
Ye-Jiang LOU
;
Zhang-Lin ZHANG
;
Gui-Ping XU
;
Pei-Min JIA
;
Jian-Hua TONG
Author Information
1. Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
- Publication Type:Journal Article
- MeSH:
CCAAT-Enhancer-Binding Protein-alpha;
metabolism;
Gene Expression Regulation, Leukemic;
drug effects;
Genes, Regulator;
drug effects;
Humans;
Interferon Regulatory Factor-1;
metabolism;
Interferon-Stimulated Gene Factor 3, gamma Subunit;
metabolism;
Intracellular Signaling Peptides and Proteins;
genetics;
Leukemia, Promyelocytic, Acute;
genetics;
STAT2 Transcription Factor;
metabolism;
Signal Transduction;
Tretinoin;
pharmacology;
Tumor Cells, Cultured
- From:
Journal of Experimental Hematology
2010;18(1):31-35
- CountryChina
- Language:Chinese
-
Abstract:
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.
