Suboptimal Action of NF-κB in Fanconi Anemia Cells Results from Low Levels of Thioredoxin
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| 024 | 7 | 0 | |a 10.1515/BC.2003.166 |2 doi |
| 035 | |a (NATIONALLICENCE)gruyter-10.1515/BC.2003.166 | ||
| 245 | 0 | 0 | |a Suboptimal Action of NF-κB in Fanconi Anemia Cells Results from Low Levels of Thioredoxin |h [Elektronische Daten] |c [M. Kontou, C. Adelfalk, M. Hirsch-Kauffmann, M. Schweiger] |
| 520 | 3 | |a Electrophoretic mobility shift assays (EMSA) revealed that under standard cell culture conditions NF-κB was induced in Fanconi anemia fibroblasts in contrast to control cells. Dithiothreitol, a potent synthetic redox potential-delivering compound, when added to growing cells, prevented this induction of NF-κB and, simultaneously, chromosomal instability was reduced. Fanconi anemia cells possess low endogenous levels of the naturally occurring antioxidant thioredoxin. Transfection of Fanconi anemia cells with thioredoxin cDNA containing a nuclear localization signal prevented both spontaneous as well as mitomycin Cinduced chromosomal instability. A promotor construct with two NF-κB binding sites in front of the CAT gene induced little CAT expression in cells with low thioredoxin content in spite of induced NF-κB. In cells with higher thioredoxin content CAT expression was increased. Cotransfection of the NF-κB-dependent CAT plasmid with the Trx/nuc-plasmid into FA fibroblasts increased the CAT expression to almost that of control cells, indicating that in this model system with diminished thioredoxin content NF-κB requires thioredoxin for binding to its specific promotor. Since Fanconi anemia cells have low thioredoxin contents, NF-κB-dependent genes are expressed insufficiently. This explains part of the pathophysiological processes observed in Fanconi anemia. | |
| 540 | |a Copyright © 2003 by Walter de Gruyter GmbH & Co. KG | ||
| 690 | 7 | |a Biochemistry |2 nationallicence | |
| 690 | 7 | |a Molecular biology |2 nationallicence | |
| 690 | 7 | |a Cellular biology |2 nationallicence | |
| 700 | 1 | |a Kontou |D M. |4 aut | |
| 700 | 1 | |a Adelfalk |D C. |4 aut | |
| 700 | 1 | |a Hirsch-Kauffmann |D M. |4 aut | |
| 700 | 1 | |a Schweiger |D M. |4 aut | |
| 773 | 0 | |t Biological Chemistry |d Walter de Gruyter |g 384/10-11(2003-11-07), 1501-1507 |x 1431-6730 |q 384:10-11<1501 |1 2003 |2 384 |o bchm | |
| 856 | 4 | 0 | |u https://doi.org/10.1515/BC.2003.166 |q text/html |z Onlinezugriff via DOI |
| 908 | |D 1 |a research article |2 jats | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1515/BC.2003.166 |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Kontou |D M. |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Adelfalk |D C. |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Hirsch-Kauffmann |D M. |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Schweiger |D M. |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Biological Chemistry |d Walter de Gruyter |g 384/10-11(2003-11-07), 1501-1507 |x 1431-6730 |q 384:10-11<1501 |1 2003 |2 384 |o bchm | ||
| 900 | 7 | |b CC0 |u http://creativecommons.org/publicdomain/zero/1.0 |2 nationallicence | |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-gruyter | ||