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Bax deficiency affects caspase-2 activation during ultraviolet radiation-induced apoptosis

Oncogene volume 23, pages 1321–1325 (2004)Cite this article

Abstract

There has been a considerable debate as to whether caspase-2 is an initiator or effector caspase. Recently, a new model of intrinsic pathway of apoptosis has been proposed, which suggests caspase-2 to be an initiator caspase. For example, ultraviolet radiation (UV) and other DNA damage-inducing agents were shown to first activate caspase-2 and then regulate the mitochondrial and postmitochondrial events. Active caspase-2 was found to engage mitochondria by promoting Bax translocation to the mitochondria. Consequently, Bax was proposed to play a central role in bridging the active caspase-2 with mitochondria by affecting mitochondrial permeability, cytochrome c release into the cytosol and caspase-9 activation. In the present study, we investigated the role of Bax in UV-induced apoptosis and caspase-2 activation. Our results indicate that UV-induced apoptosis and caspase-2 activation were diminished in Bax-deficient cells, suggesting that Bax appears to play an important role in UV-induced apoptosis as well as caspase-2 activation, and that it also appears to reside upstream of caspase-2. Bax deficiency also affected the activation of caspase-3 and -8 and abolished caspase-9 activation during UV-induced apoptosis, suggesting that the absence of caspase-9 activation may affect caspase-2, -3 and -8 activation in Bax-deficient cells. Based on our results, we propose that activation of caspases is not a linear cascade of events, but is rather connected via complex feedback loops.

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Acknowledgements

We thank Dr Bert Vogelstein (Johns Hopkins University, Baltimore, MD), for kindly providing the Bax-proficient and -deficient cells used in this study. This work was supported in part by NIH grants CA89043, CA86945 and a Department of Defense grant DMAD 170010722.

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  1. Department of Pharmacology, State University of New York, Upstate Medical University, 750 E Adams Street, Syracuse, 13210, NY, USA

    Qin He, Ying Huang & M Saeed Sheikh

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  1. Qin He
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  2. Ying Huang
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Correspondence to M Saeed Sheikh.

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He, Q., Huang, Y. & Sheikh, M. Bax deficiency affects caspase-2 activation during ultraviolet radiation-induced apoptosis. Oncogene 23, 1321–1325 (2004). https://doi.org/10.1038/sj.onc.1207212

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