The course of etoposide-induced apoptosis in Jurkat cells lacking p53 and Bax
Article first published online: 17 MAR 2006
Copyright © 2006 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 208, Issue 1, pages 55–63, July 2006
How to Cite
Karpinich, N. O., Tafani, M., Schneider, T., Russo, M. A. and Farber, J. L. (2006), The course of etoposide-induced apoptosis in Jurkat cells lacking p53 and Bax. J. Cell. Physiol., 208: 55–63. doi: 10.1002/jcp.20638
- Issue published online: 21 APR 2006
- Article first published online: 17 MAR 2006
- Manuscript Accepted: 31 JAN 2006
- Manuscript Received: 7 SEP 2005
- National Institutes of Health. Grant Number: DK 38305
Jurkat T-lymphocytes lack p53 and Bax but contain p73 and Bid and are killed by etoposide (ETO). With ETO c-abl is phosphorylated and phosphorylated p73 increased. Translocation of full-length Bid to mitochondria follows, with induction of the mitochondrial permeability transition (MPT) and release of cytochrome c into the cytosol. Pronounced swelling of mitochondria was evident ultrastructurally, and the MPT inhibitor cyclosporin A prevented the release of cytochrome c. Overexpression of Bcl-2 prevented the translocation of Bid, the release of cytochrome c, and cell death. The pan-caspase inhibitor ZVAD-FMK prevented the cell killing, but not the initial release of cytochrome c. An accumulation of tBid occurred at later times in association with Bid degradation. A sequence is proposed that couples DNA damage to Bid translocation via activation of c-abl and p73. Bid translocation induces the MPT, the event that causes release of cytochrome c, activation of caspases, and cell death. © 2006 Wiley-Liss, Inc.