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Sci. Signal., 18 March 2008
Vol. 1, Issue 11, p. ec99
[DOI: 10.1126/stke.111ec99]

EDITORS' CHOICE

Cell Biology Codependents in the Stress Response

Annalisa VanHook

Science Signaling, AAAS, Washington, DC 20005, USA

Exposure to stresses, such as heat shock or toxins, causes protein processing dysfunction in the endoplasmic reticulum (ER). If proper processing cannot be restored, the cell responds by initiating apoptosis. Qi and Mochly-Rosen used a combination of cell culture and in vivo experiments to investigate the role of protein kinase C {delta} (PKC{delta}) and the Abl tyrosine kinase in relaying the apoptotic signal from ER to mitochondria, where apoptosis is initiated. PKC{delta} and Abl, proapoptotic proteins with stress-dependent subcellular localization dynamics, are known to interact under conditions of stress. The authors coimmunoprecipitated Abl and PKC{delta} from ER cell fractions of cells treated with the toxin tunicamycin to induce ER stress and found that PKC{delta} was not activated in stressed cells when Abl transcripts were depleted by RNA interference. Expression and catalytic activity of both PKC{delta} and Abl were required to induce apoptosis, as measured by c-Jun N-terminal kinase (JNK) signaling activation and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay. The subcellular dynamics and functional interaction of PKC{delta} and Abl were also supported by an in vivo rat stroke model. The authors propose a model in which ER stress induces the translocation of PKC{delta} to the ER, where it is activated by Abl. The PKC{delta}-Abl complex transduces the apoptotic signal to mitochondria by activating the JNK cascade. Whether JNK activation occurs in the ER, cytoplasm, or mitochondria is not known, nor is it known whether PKC{delta} and Abl interact directly or whether they are part of a larger complex.

X. Qi, D. Mochly-Rosen, The PKC{delta}-Abl complex communicates ER stress to the mitochondria – an essential step in subsequent apoptosis. J. Cell Sci. 121, 804-813 (2008). [Abstract] [Full Text]

Citation: A. VanHook, Codependents in the Stress Response. Sci. Signal. 1, ec99 (2008).


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