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Sci. STKE, 28 August 2001
Vol. 2001, Issue 97, p. tw5
[DOI: 10.1126/stke.2001.97.tw5]

EDITORS' CHOICE

Apoptosis Abl to Kill in Mitochondria

The c-Abl tyrosine kinase functions in multiple locations within the cell to promote apoptosis in response to various stress stimuli. In the nucleus, c-Abl contributes to apoptotic signals in response to genotoxic stress or DNA damage, and in the cytoplasm, activation of c-Abl occurs in response to oxidative stress. Now Ito et al. present evidence that c-Abl also has a role in the control of cell death by the "unfolded protein response" in the endoplasmic reticulum (ER). They show by confocal microscopy, electron microscopy, and subcellular fractionation that c-Abl is localized to the ER in Rat1 fibroblasts. Furthermore, when ER stress was induced by treatment of cells with the calcium ionophore A23187 or with brefeldin A (which blocks transport of proteins from the ER to the Golgi), the amount of c-Abl in the ER decreased, and activated c-Abl accumulated in the mitochondria. In mouse embryo fibroblasts lacking c-Abl, A23187 and brefeldin A failed to cause release of cytochrome c from the mitochondria or apoptosis. Stable transfection of such cells with c-Abl restored the apoptotic response to ER stress. The results indicate that accumulation of excess proteins or unfolded proteins in the ER causes translocation of c-Abl from the ER to the mitochondria, where the activated kinase causes release of cytochrome c and consequent apoptosis.

Y. Ito, P. Pandey, N. Mishra, S. Kumar, N. Narula, S. Kharbanda, S. Saxena, D. Kufe, Targeting of the c-Abl tyrosine kinase to mitochondria in endoplasmic reticulum stress-induced apoptosis. Mol. Cell. Biol. 21, 6233-6242 (2001). [Abstract] [Full Text]

Citation: Abl to Kill in Mitochondria. Sci. STKE 2001, tw5 (2001).


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