Open AccessRole of c‐Fos/JunD in protecting stress‐induced cell death
Author(s) -
Zhou H.,
Gao J.,
Lu Z. Y.,
Lu L.,
Dai W.,
Xu M.
Publication year - 2007
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/j.1365-2184.2007.00444.x
Subject(s) - mapk/erk pathway , programmed cell death , activator (genetics) , microbiology and biotechnology , transcription factor , transfection , electrophoretic mobility shift assay , chemistry , apoptosis , cell growth , c jun , signal transduction , biology , biochemistry , gene
. Objective : The exposure of mammalian cells to extracellular stress induces the expression of immediate early genes such as c‐fos and c‐jun and activates transcription factor activator protein‐1 (AP‐1). The purpose of the current study was to investigate the role of c‐Fos and JunD in stress‐induced cell death. Materials and methods : We exposed cultured primary mouse embryonic fibroblasts (MEF) to ultraviolet light (UV‐C) or hydrogen peroxide (H 2 O 2 ). Induction of c‐Fos and JunD and activation of MAPK/ERK1/2 signalling in the presence or absence of a MAPK inhibitor were analyzed by western blotting. Activation of AP‐1 transcription factors was detected by the electrophoretic mobility shift assay and immunoprecipitation. Cell death was measured by changes in caspase 3 activities and nuclear morphology. Effects of c‐Fos and JunD expression on cell death were investigated by transfection. Results : We found that the exposure of cultured primary MEF cells to UV or H 2 O 2 caused a significant increase in c‐Fos and JunD protein levels. In addition, these two proteins formed complexes with each other and contributed to activation of AP‐1 transcription complexes. More importantly, under both stress conditions, overexpression of JunD alone or overexpression of both c‐Fos and JunD reduced caspase 3 activity and cell death. At the same time, UV irradiation activated the MAPK/ERK1/2 signalling pathway. The suppression of MEK1/ERK1/2 activation inhibited UV‐induced expression of c‐Fos and JunD and increased caspase 3 activity and cell death. Conclusion : Our results suggest that both UV and H 2 O 2 induce the activation of c‐Fos/JunD AP‐1 complexes resulting in the prevention of cell death. Moreover, UV irradiation‐induced increases in c‐Fos/JunD expression in primary MEF cells are mediated through the activation of the MAPK/ERK1/2 signalling pathway.