Pan Xiao-Rong, Lou Ye-Jiang, Zhang Zhang-Lin, Xu Gui-Ping, Jia Pei-Min, Tong Jian-Hua
Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2010 Feb;18(1):31-5.
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.
为了研究全反式维甲酸（ATRA）诱导rig-g基因表达的分子机制，并更好地理解ATRA在急性早幼粒细胞白血病（APL）细胞分化过程中的信号转导，采用荧光素酶报告基因检测、免疫共沉淀和染色质免疫沉淀技术来阐明直接启动rig-g基因表达的基本转录因子。结果显示，在NB4细胞中，ATRA能以不同动力学上调STAT2、IRF-9和IRF-1的表达。IRF-9能够与STAT2相互作用形成复合物，该复合物可结合rig-g基因启动子并触发rig-g表达。单独的IRF-1也能激活含有rig-g基因启动子的报告基因，但C/EBPα能强烈抑制IRF-1的这种转录活性。结论是，在ATRA诱导的APL细胞分化过程中，IRF-1首先被ATRA上调，然后IRF-1随着C/EBPα的下调增加IRF-9和STAT2的蛋白水平。IRF-9和STAT2的复合物是诱导rig-g基因的主要转录因子。本研究将有助于更好地理解ATRA在APL细胞分化过程中的信号转导网络。
