|
MBF1 role in the oxidative stress defense
|
| EMBO Journal September 2004 |
| Hirose Laboratory, Division of Gene Expression |
Coactivator MBF1 preserves the redox-dependent AP-1 activity during oxidative stress in Drosophila
Jindara M, Gaziova I, Uhlirova M, Okabe M, Hiromi Y, Hirose S. EMBO Journal, 23, in press, 2004
Basic leucine zipper proteins Jun and Fos form the dimerictranscription 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 Djun 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 (H2O2). An AP-1-dependent epithelial closure becomes sensitive to H2O2 in flies lacking MBF1. We conclude that by preserving the redox-sensitive AP-1 activity, MBF1 provides an advantage during oxidative stress.
 |
|
MBF1 role in the oxidative stress defense
Basic leucine zipper proteins Jun and Fos form the dimeric transcription factor AP-1, essential for oxidative stress defense. AP-1 activity is controlled by the redox state of critical cystein residues within the basic regions of Jun and Fos. By contrast, the conserved coactivator MBF1 prevents the oxidative modification of the cystein through direct interaction with the basic region of Jun, and contributes to oxidative stress defense and long lifespan.
|
Entrez PubMed |
|
