RRC ID 322
Author Jindra M, Gaziova I, Uhlirova M, Okabe M, Hiromi Y, Hirose S.
Title Coactivator MBF1 preserves the redox-dependent AP-1 activity during oxidative stress in Drosophila.
Journal EMBO J
Abstract 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 (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.
Volume 23(17)
Pages 3538-47
Published 2004-9-1
DOI 10.1038/sj.emboj.7600356
PII 7600356
PMID 15306851
PMC PMC516628
MeSH Amino Acid Sequence Animals Binding Sites Cysteine / chemistry Drosophila / genetics Drosophila / metabolism* Drosophila Proteins / chemistry Drosophila Proteins / genetics Drosophila Proteins / metabolism* Molecular Sequence Data Mutation Oxidation-Reduction Oxidative Stress Proto-Oncogene Proteins c-fos / chemistry Proto-Oncogene Proteins c-fos / genetics Proto-Oncogene Proteins c-fos / metabolism Proto-Oncogene Proteins c-jun / chemistry Proto-Oncogene Proteins c-jun / genetics Proto-Oncogene Proteins c-jun / metabolism Recombinant Proteins / chemistry Recombinant Proteins / genetics Recombinant Proteins / metabolism Trans-Activators / chemistry Trans-Activators / genetics Trans-Activators / metabolism* Transcription Factor AP-1 / chemistry Transcription Factor AP-1 / genetics Transcription Factor AP-1 / metabolism*
IF 11.227
Times Cited 41