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Regulation of HIF-1α activity by overexpression of thioredoxin is independent of thioredoxin reductase status

  • Research Article
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Molecules and Cells

Abstract

Under hypoxic conditions, cells activate a transcriptional response mainly driven by hypoxia-inducible factors (HIFs). HIF-1α stabilization and activity are known to be regulated by thioredoxin 1 (Txn1), but how the thioredoxin system regulates the hypoxic response is unknown. By examining the effects of Txn1 overexpression on HIF-1α function in HeLa, HT-29, MCF-7 and EMT6 cell lines, we found that this oxidoreductase did not stabilize HIF-1α, yet could increase its activity. These effects were dependent on the redox function of Txn1. However, Txn1 deficiency did not affect HIF-1α hypoxic-stabilization and activity, and overexpression of thioredoxin reductase 1 (TR1), the natural Txn1 reductase, had no influence on HIF-1α activity. Moreover, overexpression of Txn1 in TR1 deficient HeLa and EMT6 cells was still able to increase HIF-1α hypoxic activity. These results indicate that Txn1 is not essential for HIF-1α hypoxic stabilization or activity, that its overexpression can increase HIF-1α hypoxic activity, and that this effect is observed regardless of TR1 status. Thus, regulation of HIF-1α by the thioredoxin system depends on the specific levels of this system’s major components.

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Author notes

  1. Salvador Naranjo-Suarez

    Present address: Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, John Hopkins Medical Institution, Baltimore, MD, 21231, USA

Authors and Affiliations

  1. Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, Center for Cancer Research, National Institutes of Health, Bethesda, MD, 20892, USA

    Salvador Naranjo-Suarez, Bradley A. Carlson, Ryuta Tobe, Min-Hyuk Yoo & Dolph L. Hatfield

  2. Department of Biological Sciences, Towson University, Towson, MD, 21252, USA

    Petra A. Tsuji

  3. Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, 02115, USA

    Vadim N. Gladyshev

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  1. Salvador Naranjo-Suarez
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  2. Bradley A. Carlson
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Correspondence to Dolph L. Hatfield.

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Naranjo-Suarez, S., Carlson, B.A., Tobe, R. et al. Regulation of HIF-1α activity by overexpression of thioredoxin is independent of thioredoxin reductase status. Mol Cells 36, 151–157 (2013). https://doi.org/10.1007/s10059-013-0121-y

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  • DOI: https://doi.org/10.1007/s10059-013-0121-y

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