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Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress

Abstract

The ability to respond to perturbations in endoplasmic reticulum (ER) function is a fundamentally important property of all cells, but ER stress can also lead to apoptosis. In settings of chronic ER stress, the associated apoptosis may contribute to pathophysiological processes involved in a number of prevalent diseases, including neurodegenerative diseases, diabetes, atherosclerosis and renal disease. The molecular mechanisms linking ER stress to apoptosis are the topic of this review, with emphases on relevance to pathophysiology and integration and complementation among the various apoptotic pathways induced by ER stress.

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Figure 1: Prolonged activation of IRE1 may promote apoptosis.
Figure 2: Pathways through which prolonged activation of CHOP may promote apoptosis.
Figure 3: Examples of integration among the UPR apoptosis pathways.
Figure 4: Examples of therapeutic strategies to prevent cell death in the setting of pathologic, prolonged ER stress.

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Acknowledgements

I.T. and D.R. gratefully acknowledge current and past members of their laboratories who contributed to the studies described herein. This work was supported by National Institutes of Health Grants HL087123, HL075662, and HL054591 to I.T. and by a Wellcome Trust Principal Research Fellowship to D.R.

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Correspondence to Ira Tabas.

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Tabas, I., Ron, D. Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Biol 13, 184–190 (2011). https://doi.org/10.1038/ncb0311-184

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