title: Signal Transduction in TNF-alpha-induced c-jun Gene Expression.
abstract: Our previous studies demonstrated that p38 mitogen-activated protein (MAP) kinase regulated the c-jun protein expression through phosphorylation of transcription factors of myocyte enhancer factors 2 (MEF2) family. There was a MEF2 binding site in the promoter of c-jun gene. Members of the MEF2 family of trans-cription factors bound as homo- and heterodimers to this MEF2 binding site. Here the potential role of the p38 and BMK1 MAP kinases in the regulation of c-jun expression induced by TNF-alpha was examined. It was shown that p38 MAP kinase up-regulated the transcription activity of MEF2A, while BMK1 MAP kinase up-regulated not only the transcription activity of MEF2A, but also MEF2D. The p38 and BMK1 MAP kinases had coordinated effect on the regulation of c-jun transcription. TNF-alpha induced the formation of MEF2A/MEF2D hete-rodimer. Over-expression of homodimer of MEF2 proteins inhibited c-jun transcription induced by TNF-alpha, while over-expression of heterodimer MEF2A/MEF2D enhanced c-jun transcription induced by TNF-alpha. Phosphorylation of MEF2A and MEF2D by p38 and BMK1 respectively appeared very important in TNF-alpha induced MEF2A/MEF2D heterodimer formation to enhance c-jun gene expression.
authors.affiliation: Department of Pathophysiology and Key Laboratory for Shock and Microcirculation of PLA, The First Military Medical University, Guangzhou 510515, China. yjiang@public.guangzhou.gd.cn
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Ya-Wei
authors.initials: YW
authors.lastname: Liu
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Liu
authors.forename: Ke-Sen
authors.initials: KS
authors.lastname: Zhao
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang