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Signal Transduction in TNF-alpha-induced c-jun Gene Expression
Ming Zhao1, Ya-Wei Liu, Ai-Hua Liu
1Department of Pathophysiology and Key Laboratory for Shock and Microcirculation of PLA, The First Military Medical University, Guangzhou 510515, China. yjiang@public.guangzhou.gd.cn
Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao Acta Biochimica Et Biophysica Sinica
|June 21, 2002
Summary
p38 and BMK1 mitogen-activated protein (MAP) kinases regulate c-jun gene expression via myocyte enhancer factors 2 (MEF2) transcription factors. Their coordinated action and MEF2A/MEF2D heterodimer formation are crucial for TNF-alpha-induced c-jun expression.
Area of Science:
- Molecular Biology
- Cell Signaling
- Gene Regulation
Background:
- p38 MAP kinase previously shown to regulate c-jun protein expression via MEF2 transcription factors.
- MEF2 family members bind to a specific site in the c-jun promoter as homo- and heterodimers.
Purpose of the Study:
- To investigate the roles of p38 and BMK1 MAP kinases in TNF-alpha-induced c-jun expression.
- To elucidate the mechanism involving MEF2 transcription factors in this process.
Main Methods:
- Examined the effects of p38 and BMK1 MAP kinases on MEF2A and MEF2D transcription activity.
- Analyzed TNF-alpha-induced MEF2A/MEF2D heterodimer formation.
- Investigated the impact of MEF2 homodimer and heterodimer overexpression on c-jun transcription.
Main Results:
- p38 MAP kinase up-regulated MEF2A transcription activity.
- BMK1 MAP kinase up-regulated both MEF2A and MEF2D transcription activity.
- TNF-alpha induced MEF2A/MEF2D heterodimer formation, enhancing c-jun transcription, while homodimers inhibited it.
Conclusions:
- p38 and BMK1 MAP kinases coordinate to regulate c-jun transcription.
- Phosphorylation of MEF2A and MEF2D by p38 and BMK1, respectively, is critical for TNF-alpha-induced MEF2A/MEF2D heterodimer formation and subsequent c-jun gene expression.