The endoplasmic reticulum in apoptosis and autophagy: role of the BCL-2 protein family.

Abstract:

:Apoptosis is essential for normal development and maintenance of homeostasis, and disruption of apoptotic pathways is associated with multiple disease states, including cancer. Although initially identified as central regulators of apoptosis at the level of mitochondria, an important role for BCL-2 proteins at the endoplasmic reticulum is now well established. Signaling pathways emanating from the endoplasmic reticulum (ER) are involved in apoptosis initiated by stimuli as diverse as ER stress, oncogene expression, death receptor (DR) ligation and oxidative stress, and the BCL-2 family is almost invariably implicated in the regulation of these pathways. This also includes Ca(2+)-mediated cross talk between ER and mitochondria during apoptosis, which contributes to the mitochondrial dynamics that support the core mitochondrial apoptosis pathway. In addition to the regulation of apoptosis, BCL-2 proteins at the ER also regulate autophagy, a survival pathway that limits metabolic stress, genomic instability and tumorigenesis. In cases where apoptosis is inhibited, however, prolonged autophagy can lead to cell death. This review provides an overview of ER-associated apoptotic and autophagic signaling pathways, with particular emphasis on the BCL-2 family proteins.

journal_name

Oncogene

journal_title

Oncogene

authors

Heath-Engel HM,Chang NC,Shore GC

doi

10.1038/onc.2008.309

subject

Has Abstract

pub_date

2008-10-27 00:00:00

pages

6419-33

issue

50

eissn

0950-9232

issn

1476-5594

pii

onc2008309

journal_volume

27

pub_type

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