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Thioredoxin, a regulator of gene expression

Oncogene volume 23, pages 2146–2152 (2004)Cite this article

Abstract

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 IκBα/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.

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Acknowledgements

RW, RW and AP thank Dr Bernhard Korn and Dr Christian Maercker from the RZPD Heidelberg for excellent support and critical discussions and Ingrid Brück for technical support. MK, CA, MH-K and MS thank Dr Susann Schweiger for kindly providing GAPDH antibodies and Dr Vera Kalkscheuer for GAPDH primers. We are indebted to Klaus Hennig who purified human thioredoxin and to Dr Rossi who prepared polyclonal antibodies against this protein. We also thank Dr Danny Hirsch-Kauffmann Jokl, New York for editing the manuscript. The work was possible through grants by the Thyssen-foundation (20002084). It was performed in the frame of EUROS, a European research program on oxidative stress contract #BMH4-CT98-3107 BIOMEDZ CE DGXII. We thank the coordinator of this program Dr Giovanni Pagano, Naples, for stimulating discussions.

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Author notes

  1. Caroline Adelfalk & Monica Hirsch-Kauffmann

    Present address: Max-Planck-Institut für Molekulare Genetik, Ihnestr. 73, Berlin, D-14195, Germany

Authors and Affiliations

  1. Institut für Biochemie, Freie Universität Berlin, Thielallee 63,, Berlin, D-14195, Germany

    Maria Kontou, Caroline Adelfalk, Monica Hirsch-Kauffmann & Manfred Schweiger

  2. Department of Molecular Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 580, Heidelberg, D-69120, Germany

    Rainer D Will, Rainer Wittig & Annemarie Poustka

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  1. Maria Kontou
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Correspondence to Manfred Schweiger.

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Kontou, M., Will, R., Adelfalk, C. et al. Thioredoxin, a regulator of gene expression. Oncogene 23, 2146–2152 (2004). https://doi.org/10.1038/sj.onc.1207334

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