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

Oncogene. 2006 Mar 23;25(13):1903-13. doi: 10.1038/sj.onc.1209218.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Apoptosis*
  • Blotting, Northern
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • DNA Mutational Analysis
  • Dexamethasone / pharmacology*
  • Gene Expression Profiling
  • Glucocorticoids / pharmacology*
  • Humans
  • Lymphoma, T-Cell / genetics
  • Lymphoma, T-Cell / pathology*
  • RNA, Messenger
  • Thioredoxins / genetics
  • Tumor Cells, Cultured


  • Anti-Inflammatory Agents
  • Carrier Proteins
  • Glucocorticoids
  • RNA, Messenger
  • TXNIP protein, human
  • Thioredoxins
  • Dexamethasone