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

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

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Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS MLKL, A NEW ACTOR OF UVB-INDUCED APOPTOSIS IN HUMAN DIPLOID DERMAL FIBROBLASTS Article Open access 14 May 2024 CASPASE-2

REGULATES S-PHASE CELL CYCLE EVENTS TO PROTECT FROM DNA DAMAGE ACCUMULATION INDEPENDENT OF APOPTOSIS Article 30 October 2021 THE E3 LIGASE UBR2 REGULATES CELL DEATH UNDER CASPASE DEFICIENCY

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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. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * 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 Authors * Qin He View author publications You can also search for this author inPubMed Google Scholar * Ying Huang View

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CORRESPONDING AUTHOR Correspondence to M Saeed Sheikh. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 14 August

2003 * Revised: 11 September 2003 * Published: 01 December 2003 * Issue Date: 12 February 2004 * DOI: https://doi.org/10.1038/sj.onc.1207212 SHARE THIS ARTICLE Anyone you share the following

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SharedIt content-sharing initiative KEYWORDS * caspase-2 * ultraviolet radiation * Bax deficiency * colon cancer cells