Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 55-63 |
| Number of pages | 9 |
| Journal | Journal of Cellular Physiology |
| Volume | 208 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jul 2006 |
Fingerprint
ASJC Scopus subject areas
- Cell Biology
- Clinical Biochemistry
- Physiology
Cite this
The course of etoposide-induced apoptosis in jurkat cells lacking p53 and Bax. / Karpinich, Natalie O.; Tafani, Marco; Schneider, Timothy; Russo, Matteo A.; Farber, John L.
In: Journal of Cellular Physiology, Vol. 208, No. 1, 07.2006, p. 55-63.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The course of etoposide-induced apoptosis in jurkat cells lacking p53 and Bax
AU - Karpinich, Natalie O.
AU - Tafani, Marco
AU - Schneider, Timothy
AU - Russo, Matteo A.
AU - Farber, John L.
PY - 2006/7
Y1 - 2006/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33744933705&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33744933705&partnerID=8YFLogxK
U2 - 10.1002/jcp.20638
DO - 10.1002/jcp.20638
M3 - Article
C2 - 16547931
AN - SCOPUS:33744933705
VL - 208
SP - 55
EP - 63
JO - Journal of cellular and comparative physiology
JF - Journal of cellular and comparative physiology
SN - 0021-9541
IS - 1
ER -