Activator protein 1 promotes the transcriptional activation of IRAK-M

作者：Jin, Peipei; Bo, Lulong; Liu, Yongjian; Lu, Wenbin; Lin, Shengwei; Bian, Jinjun^*; Deng, Xiaoming

来源：Biomedicine & Pharmacotherapy, 2016, 83: 1212-1219.

DOI：10.1016/j.biopha.2016.08.024

• IRAK-M
• Promoter
• Gene transcription
• AP-1

Interleukin-1 receptor-associated kinase M (IRAK-M) is a well-known negative regulator for Toll-like receptor signaling, which can regulate immune homeostasis and tolerance in a number of pathological settings. However, the mechanism for IRAK-M regulation at transcriptional level remains largely unknown. In this study, a 1.4 kb upstream sequence starting from the major IRAK-M transcriptional start site was cloned into luciferase reporter vector pGL3-basic to construct the full-length IRAK-M promoter. Luciferase reporter plasmids harboring the full-length and the deletion mutants of IRAK-M were transfected into 293T and A549 cells, and their relative luciferase activity was measured. The results demonstrated that activator protein 1(AP-1) cis-element plays a crucial role in IRAK-M constitutive gene transcription. Silencing of c-Fos and/or c-Jun expression suppressed the IRAK-M promoter activity as well as its mRNA and protein expressions. As a specific inhibitor for AP-1 activation, SP600125 also significantly suppressed the basal transcriptional activity of IRAK-M, the binding activity of c-Fos/c-Jun with IRAK-M promoter, and IRAK-M protein expression. Taken together, the result of this study highlights the importance of AP-1 in IRAK-M transcription, which offers more information on the role of IRAK-M in infectious and non-infectious diseases.

• 出版日期2016-10
• 单位南京大学; 中国人民解放军第二军医大学