Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

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


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).

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882