title: Activator protein 1 promotes the transcriptional activation of IRAK-M.
abstract: 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 1.4kb 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.
authors: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Peipei
authors: P
authors: Jin
authors: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Lulong
authors: L
authors: Bo
authors: College of Life Science, Nanjing University, Nanjing 210006, China.
authors: Yongjian
authors: Y
authors: Liu
authors: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Wenbin
authors: W
authors: Lu
authors: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Shengwei
authors: S
authors: Lin
authors: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, Shanghai 200433, China; College of Life Science, Nanjing University, Nanjing 210006, China. Electronic address: jinjunbicu@163.com.
authors: Jinjun
authors: J
authors: Bian
authors: Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Xiaoming
authors: X
authors: Deng
mesh_terms: D000072283:A549 Cells; D001483:Base Sequence; D001665:Binding Sites / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000096:biosynthesis* / Q000235:genetics*; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*
chemical_list: D018808:Transcription Factor AP-1; C507771:IRAK3 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases
keywords: AP-1; Gene transcription; IRAK-M; Promoter