Thapsigargin-induced apoptosis involves Cabin1-MEF2-mediated induction of Nur77

Weifeng Liu, Hong Duk Youn, Jun O. Liu

Research output: Contribution to journalArticlepeer-review

Abstract

Thapsigargin (TG), which inhibits endoplasmic reticulum-dependent Ca2+-ATPase and thereby increases cytosolic Ca2+, has been reported to cause apoptosis in T lymphocytes and other cell types. In this study, we investigated the molecular mechanisms that are involved in the apoptosis induced by TG in T cell hybridomas. Exposure to TG results in rapid induction of the orphan steroid receptor, Nur77, accompanied by apoptosis of T cell hybridomas. The expression of Nur77 in response to TG treatment is sensitive to cyclosporin A, implicating that activation of calcineurin is necessary for Nur77 expression. The TG-induced Nur77 expression is also inhibited by overexpression of Cabin1, an endogenous inhibitor of calcineurin and a corepressor of the transcription factor MEF2, suggesting that MEF2 activation is required for Nur77 expression. These results suggest that induction of Nur77 expression and apoptosis by TG are mediated by the same signaling pathways that are involved in T cell receptor-mediated thymocyte apoptosis, including the calcineurin pathway and Cabin1-MEF2 pathway.

Original languageEnglish (US)
Pages (from-to)1757-1764
Number of pages8
JournalEuropean Journal of Immunology
Volume31
Issue number6
DOIs
StatePublished - Jun 28 2001

Keywords

  • Apoptosis
  • Cabin 1
  • Nur77
  • T cell
  • Thapsigargin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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