Thioredoxin, a regulator of gene expression
| Autor: | Annemarie Poustka, Maria Kontou, Rainer Wittig, Manfred Schweiger, Rainer Will, Monica Hirsch-Kauffmann, Caroline Adelfalk |
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| Rok vydání: | 2004 |
| Předmět: |
Cell Extracts
Cancer Research animal structures Blotting Western Thioredoxins stomatognathic system Gene expression Genetics Humans Molecular Biology Cells Cultured Glyceraldehyde 3-phosphate dehydrogenase Cell Line Transformed Regulator gene Expression vector biology Reverse Transcriptase Polymerase Chain Reaction Transfection Fibroblasts Blotting Northern Molecular biology IκBα Gene Expression Regulation Cancer cell biology.protein Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) Thioredoxin |
| Zdroj: | Oncogene. 23:2146-2152 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1207334 |
| Popis: | Cancer cells have high levels of thioredoxin (Trx) and of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Cells from patients with the cancer-prone disease Fanconi anemia (FA) exhibit reduced Trx levels. We found the activity of GAPDH to correlate directly with the endogenous Trx content and mRNA transcripts for GAPDH and TRx reduced in FA cells. The treatment of cells with reduced human Trx stimulated the synthesis of GAPDH mRNA. Similarly, the transfection of cells with an expression plasmid for Trx increased GAPDH mRNA synthesis. Trx treatment of cells and subsequent analysis of the differential gene expression by human cDNA arrays containing about 50 000 different PCR products resulted in more than 300 up- or downregulated genes. Two representative genes, GAPDH and IkappaBalpha/MAD-3, were further investigated to confirm their stimulation by Trx. Trx besides being the major carrier of redox potential of cells is also a regulator of gene expression on the transcriptional level. By regulation via Trx, cells are able to adapt to the prevailing redox conditions. These findings also enlighten the pathophysiology of FA in the respect that the characteristic diminution of Trx that results in the dysregulation of gene expression is a basis for the major symptoms of this disease. |
| Databáze: | OpenAIRE |
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