Signal Transduction in
TNF-α-induced c-jun Gene
Expression
ZHAO Ming, LIU Ya-Wei, LIU Ai-Hua, ZHAO Ke-Sen, JIANG Yong*
( Department of Pathophysiology and Key Laboratory for Shock and
Microcirculation of PLA, The
First Military Medical University, Guangzhou 510515, China )
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-α 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-α induced
the formation of MEF2A/MEF2D hete-rodimer. Over-expression of homodimer of MEF2
proteins inhibited c-jun transcription
induced by TNF-α, while over-expression of heterodimer MEF2A/MEF2D enhanced c-jun transcription
induced by TNF-α. Phosphorylation of MEF2A and MEF2D by p38 and BMK1
respectively appeared very important in TNF-α induced MEF2A/MEF2D heterodimer
formation to enhance c-jun gene expression.
Key words tumor necrosis
factor-α； mitogen-activated protein
kinase； signal transduction； inflammation； gene expression
Received:
November 12, 1999 Accepted: January 4, 2000
This study was supported in part by National Science Fund for
Distinguished Young Scholars(39870332), Grants from National science Foundation
of China (39830400、39800074、39870332), Natural science Foundation of
Guangdong Province (980207) and Outstanding Young Investigator Award of PLA
(98J003)
* Corresponding author: Tel, 86-20-85148424; Fax,
86-20-87705671; e-mail,[email protected]