| Autor: |
Makin GW; Cancer Research Campaign Cellular and Molecular Pharmacology Group, School of Biological Sciences, University of Manchester, Manchester M13 9PT, UK., Corfe BM, Griffiths GJ, Thistlethwaite A, Hickman JA, Dive C |
| Jazyk: |
angličtina |
| Zdroj: |
The EMBO journal [EMBO J] 2001 Nov 15; Vol. 20 (22), pp. 6306-15. |
| DOI: |
10.1093/emboj/20.22.6306 |
| Abstrakt: |
Sequential steps in the activation of the pro-apoptotic protein Bax are described for cells with different sensitivity to cytotoxins. SH-EP1 and SH-SY5Y human neuroblastoma cells, derived from a single precursor cell line, differed in their sensitivity to taxol but showed the same sensitivity to cisplatin. Both drugs, in both cell lines, induced exposure of a constitutively occluded N-terminal epitope of Bax. This was reversible and occurred before the translocation of cytosolic Bax to mitochondria. The N-terminal change in Bax, its subsequent movement to mitochondria and its dimerization/complex formation were insufficient for commitment to death, occurring in the same proportion of cells that either maintained (SH-SY5Y) or lost (SH-EP1) clonogenic survival after taxol treatment. Suppression of taxol-induced apoptosis occurred upstream of cytochrome c release from mitochondria in SH-SY5Y cells. The data suggest that a further drug damage-induced event occurs after Bax dimerization/complex formation but prior to cytochrome c release. This event was absent in the taxol-resistant cells. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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