Glucocorticoid-induced apoptosis revisited: A novel role for glucocorticoid receptor translocation to the mitochondria

Ronit Vogt Sionov, Shlomit Kfir, Elazar Zafrir, Orly Cohen, Yael Zilberman, Eitan Yefenof

Research output: Contribution to journalReview articlepeer-review

Abstract

Recent data cast new light on the mechanisms by which glucocorticoids (GCs) elicit apoptosis of thymocytes and leukemia cells. Here we attempt to integrate recent studies by others and us, which provide a novel insight to this apoptotic process. In the last few years it was made clear that there is a tight cooperation between genomic and non-genomic effects exerted by GC receptors (GRs). GC invokes major alterations in the gene expression profile through GR-mediated transactivation and transrepression, which ultimately tip the balance between pro-survival and pro-apoptotic proteins. Although essential in shaping the cell's proteome, these genomic effects are insufficient to elicit apoptotic death and additional signals are required for activating the pro-apoptotic proteins. Several non-genomic effects have been described that occur immediately following exposure to GC, which are imperative for the induction of apoptosis. We have recently observed that GC induces instant GR translocation to the mitochondria in GC-sensitive, but not in GC-resistant, T lymphoid cells. This response contrasts the nuclear translocation of GR occurring in both cell types. We propose that the sustained elevation of GR in the mitochondria following GC exposure is crucial for triggering apoptosis.

Original languageEnglish
Pages (from-to)1017-1026
Number of pages10
JournalCell Cycle
Volume5
Issue number10
DOIs
StatePublished - 15 May 2006
Externally publishedYes

Keywords

  • Apoptosis
  • Glucocorticoid
  • Glucocorticoid receptor
  • Leukemia
  • Mitochondria
  • Non-genomic effects

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