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Oncogene. 2006 Mar 23;25(13):1903-13.

Thioredoxin-interacting protein (txnip) is a glucocorticoid-regulated primary response gene involved in mediating glucocorticoid-induced apoptosis.

Author information

1
Department of Medicine and Pharmacology, Comprehensive Cancer Center, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, OH 44106-7285, USA.

Erratum in

  • Oncogene. 2008 Feb 21;27(9):1342.

Abstract

Glucocorticoid hormones induce apoptosis in lymphoid cells. This process is transcriptionally regulated and requires de novo RNA/protein synthesis. However, the full spectrum of glucocorticoid-regulated genes mediating this cell death process is unknown. Through gene expression profiling we discovered that the expression of thioredoxin-intereacting protein (txnip) mRNA is significantly induced by the glucocorticoid hormone dexamethasone not only in the murine T-cell lymphoma line WEHI7.2, but also in normal mouse thymocytes. This result was confirmed by Northern blot analysis in multiple models of dexamethasone-induced apoptosis. The induction of txnip mRNA by dexamethasone appears to be mediated through the glucocorticoid receptor as it is blocked in the presence of RU486, a glucocorticoid receptor antagonist. Deletion and mutation analysis of the txnip promoter identified a functional glucocorticoid response element in the txnip promoter. Reporter assays demonstrated that this glucocorticoid response element was necessary and sufficient for induction of txnip by dexamethasone. Expression of a GFP-TXNIP fusion protein was sufficient to induce apoptosis in WEHI7.2 cells, and repression of endogenous txnip by RNA interference inhibited dexamethasone-induced apoptosis in WEHI7.2 cells. Together, these findings indicate that txnip is a novel glucocorticoid-induced primary target gene involved in mediating glucocorticoid-induced apoptosis.

PMID:
16301999
DOI:
10.1038/sj.onc.1209218
[Indexed for MEDLINE]

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