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Coactivator MBF1 preserves the redox‐dependent AP‐1 activity during oxidative stress in Drosophila
Author(s) -
Jindra Marek,
Gaziova Ivana,
Uhlirova Mirka,
Okabe Masataka,
Hiromi Yasushi,
Hirose Susumu
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600356
Subject(s) - biology , oxidative stress , coactivator , redox , drosophila (subgenus) , oxidative phosphorylation , microbiology and biotechnology , biochemistry , transcription factor , gene , materials science , metallurgy
Basic leucine zipper proteins Jun and Fos form the dimeric transcription factor AP‐1, essential for cell differentiation and immune and antioxidant defenses. AP‐1 activity is controlled, in part, by the redox state of critical cysteine residues within the basic regions of Jun and Fos. Mutation of these cysteines contributes to oncogenic potential of Jun and Fos. How cells maintain the redox‐dependent AP‐1 activity at favorable levels is not known. We show that the conserved coactivator MBF1 is a positive modulator of AP‐1. Via a direct interaction with the basic region of Drosophila Jun (D‐Jun), MBF1 prevents an oxidative modification (S‐cystenyl cystenylation) of the critical cysteine and stimulates AP‐1 binding to DNA. Cytoplasmic MBF1 translocates to the nucleus together with a transfected D‐Jun protein, suggesting that MBF1 protects nascent D‐Jun also in Drosophila cells. mbf1 ‐null mutants live shorter than mbf1 + controls in the presence of hydrogen peroxide (H 2 O 2 ). An AP‐1‐dependent epithelial closure becomes sensitive to H 2 O 2 in flies lacking MBF1. We conclude that by preserving the redox‐sensitive AP‐1 activity, MBF1 provides an advantage during oxidative stress.