TY - JOUR
T1 - An alternative splicing variant of the selenoprotein thioredoxin reductase is a modulator of estrogen signaling
AU - Damdimopoulos, Anastasios E.
AU - Miranda-Vizuete, Antonio
AU - Treuter, Eckardt
AU - Gustafsson, Jan Ånke
AU - Spyrou, Giannis
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/9/10
Y1 - 2004/9/10
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M402753200
DO - 10.1074/jbc.M402753200
M3 - Article
C2 - 15199063
AN - SCOPUS:4644318801
SN - 0021-9258
VL - 279
SP - 38721
EP - 38729
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 37
ER -