TITLE

Regulation of apoptosis by endoplasmic reticulum pathways

AUTHOR(S)
Breckenridge, David G.; Germaine, Marc; Mathai, Jaigi P.; Nguyen, Mai; Shore, Gordon C.
PUB. DATE
November 2003
SOURCE
Oncogene;11/24/2003 Review, Vol. 22 Issue 53, p8608
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Apoptotic programmed cell death pathways are activated by a diverse array of cell extrinsic and intrinsic signals, most of which are ultimately coupled to the activation of effector caspases. In many instances, this involves an obligate propagation through mitochondria, causing egress of critical proapoptotic regulators to the cytosol. Central to the regulation of the mitochondrial checkpoint is a complex three-way interplay between members of the BCL-2 family, which are comprised of an antiapoptotic subgroup including BCL-2 itself, and the proapoptotic BAX,BAK and BH3-domain-only subgroups. Constituents of all three of these BCL-2 classes, however, also converge on the endoplasmic reticulum (ER), an organelle whose critical contributions to apoptosis is only now becoming apparent. In addition to propagating death-inducing stress signals itself, the ER also contributes in a fundamental way to Fas-mediated apoptosis and to p53-dependent pathways resulting from DNA damage and oncogene expression. Mobilization of ER calcium stores can initiate the activation of cytoplasmic death pathways as well as sensitize mitochondria to direct proapoptotic stimuli. Additionally, the existence of BCL-2-regulated initiator procaspase activation complexes at the ER membrane has also been described. Here, we review the potential underlying mechanisms involved in these events and discuss pathways for ER-mitochondrial crosstalk pertinent to a number of cell death stimuli.Oncogene (2003) 22, 8608-8618. doi:10.1038/sj.onc.1207108
ACCESSION #
11524589

 

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