An alternative splicing variant of the selenoprotein thioredoxin reductase is a modulator of estrogen signaling

Anastasios E. Damdimopoulos, Antonio Miranda-Vizuete, Eckardt Treuter, Jan Ånke Gustafsson, Giannis Spyrou

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

The selenoprotein thioredoxin reductase (TrxR1) is an integral part of the thioredoxin system. It serves to transfer electrons from NADPH to thioredoxin leading to its reduction. Interestingly, recent work has indicated that thioredoxin reductase can regulate the activity of transcription factors such as p53, hypoxia-inducible factor, and AP-1. Here, we describe that an alternative splicing variant of thioredoxin reductase (TrxR1b) containing an LXXLL peptide motif, is implicated in direct binding to nuclear receptors. In vitro interaction studies revealed direct interaction of the TrxR1b with the estrogen receptors α and β. Confocal microscopy analysis showed nuclear colocalization of the TrxR1b with both estrogen receptor α and β in estradiol-17β-treated cells. Transcriptional studies demonstrated that TrxR1b can affect estrogen-dependent gene activation differentially at classical estrogen response elements as compared with AP-1 response elements. Based on these results, we propose a model where thioredoxin reductase directly influences the estrogen receptor-coactivator complex assembly on non-classical estrogen response elements such as AP-1. In summary, our results suggest that TrxR1b is an important modulator of estrogen signaling.

Original languageEnglish (US)
Pages (from-to)38721-38729
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number37
DOIs
StatePublished - Sep 10 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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