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Changes of the Trans ‐Activating Potential of AP‐1 Transcription Factor During Cyclosporin A‐Induced Apoptosis of Glioma and Cells Are Mediated by Phosphorylation and Alterations of AP‐1 Composition
Author(s) -
Pyrzynska Beata,
Mosieniak Grazyna,
Kaminska Bozena
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0740042.x
Subject(s) - junb , ap 1 transcription factor , apoptosis , phosphorylation , transcription factor , c jun , biology , microbiology and biotechnology , activating transcription factor , activating transcription factor 2 , kinase , promoter , gene expression , biochemistry , unfolded protein response , gene
Although the AP‐1 transcription factor is known to play a role in cell proliferation and activation, it is also involved in apoptosis of cells in response to stress, DNA‐damaging agents, or lack of survival signals. To understand how AP‐1 might contribute to distinct biological processes, we tested a hypothesis that changes in AP‐1 composition or phosphorylation state modulate its transcriptional activity during cyclosporin A‐induced apoptosis of glioma cells. The induction of AP‐1 DNA binding activity composed of c‐Jun, JunB, JunD, and ATF‐2 proteins preceded apoptosis. The compositional changes of AP‐1 were associated with an elevation of c‐Jun and JunB protein levels and the appearance of phosphorylated c‐Jun and ATF‐2 at 15‐40 h posttreatment. Immunocytochemistry and staining with Hoechst 33258 revealed an accumulation of phosphorylated c‐Jun protein in apoptotic cells. Because c‐Jun expression and transcriptional activity are stimulated by phosphorylation at Ser 63/73 by c‐Jun N‐terminal kinase (JNK), we measured JNK activities. We found prolonged induction of JNK activity in extracts from cyclosporin‐treated cells, which suggests an involvement of persistent JNK activation in the initiation of glioma cell apoptosis. We provided evidence that variations in AP‐1 composition and phosphorylation resulted in modification of trans ‐activating potential toward different promoters. Whereas collagenase AP1/TRE‐dependent transcription was down‐regulated during apoptosis, Fas ligand promoter became activated.