Cell Death and Differentiation (2002) 9, 6±19 ã 2002 Nature Publishing Group All rights reserved 1350-9047/02 $25.00 www.nature.com/cdd Review Recent insights into the mechanism of glucocorticosteroid- induced apoptosis CW Distelhorst*,1 apoptosis.1 But progress in understanding corticosteroid- induced apoptosis has lagged behind remarkable advances in 1 Division of Hematology/Oncology and Comprehensive Cancer Center, understanding other forms of apoptosis, such as that induced Departments of Medicine and Pharmacology, Case Western Reserve by the ligands of death receptors (e.g., Fas/CD95, tumor University School of Medicine and University Hospitals of Cleveland, necrosis factor). In part, this is because corticosteroid-induced Cleveland, Ohio, USA apoptosis is initiated by a steroid receptor-mediated change in * Corresponding author: CW Distelhorst, Division of Hematology/Oncology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio, gene expression, but specific genes that mediate cell death in OH 44106-4937, USA. Tel: 216-368-1175; Fax: 216-368-1166; response to corticosteroid treatment have not been identified. E-mail:
[email protected] Recent findings have shed light on events in the cell death pathway downstream from gene regulation, including the Received 20.7.01; revised 7.9.01; accepted 3.10.01 caspases responsible for the execution phase of cell death, Edited by G Nunez the unexpected involvement of the multicatalytic proteasome in the death process, the suppression of prosurvival transcrip- tion factors (e.g., AP-1, c-myc,NF-kB), and crosstalk between Abstract T cell receptor and cytokine signaling pathways. Moreover, Glucocorticosteroid hormones induce apoptosis in lympho- evidence that mitochondrial dysfunction lies downstream of cytes.