Glucocorticoid-Induced Apoptosis: Revisited: A Novel Role for Glucocorticoid Receptor Translocation to the Mitochondria |
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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 recentstudies by others and us, which provide a novel insight to this apoptotic process. In thelast few years it was made clear that there is a tight cooperation between genomic andnon-genomic effects exerted by GC receptors (GRs). GC invokes major alterations in thegene expression profile through GR-mediated transactivation and transrepression, whichultimately tip the balance between pro-survival and pro-apoptotic proteins. Althoughessential in shaping the cell’s proteome, these genomic effects are insufficient to elicitapoptotic death and additional signals are required for activating the pro-apoptoticproteins. Several non-genomic effects have been described that occur immediatelyfollowing exposure to GC, which are imperative for the induction of apoptosis. We haverecently observed that GC induces instant GR translocation to the mitochondria in GCsensitive,but not in GC-resistant, T lymphoid cells. This response contrasts the nucleartranslocation of GR occurring in both cell types. We propose that the sustained elevationof GR in the mitochondria following GC exposure is crucial for triggering apoptosis. |
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