| Autor: |
McGrath LB; UCD School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland, margaret.mcgee@ucd.ie., Onnis V, Campiani G, Williams DC, Zisterer DM, Mc Gee MM |
| Jazyk: |
angličtina |
| Zdroj: |
Apoptosis : an international journal on programmed cell death [Apoptosis] 2006 Sep; Vol. 11 (9), pp. 1473-87. |
| DOI: |
10.1007/s10495-006-8968-4 |
| Abstrakt: |
We have previously reported that the pro-apoptotic pyrrolobenzoxazepine, PBOX-6, induces apoptosis in chronic myelogenous leukaemia (CML) cells which is accompanied by oligonucleosomal DNA fragmentation. In this study we show that PBOX-6-induced oligonucleosomal DNA fragmentation occurs in the absence of caspase and CAD activation in CML cells. Dissection of the signalling pathway has revealed that induction of apoptosis requires the upstream activation of a trypsin-like serine protease that promotes the phosphorylation and inactivation of anti-apoptotic Bcl-2. In addition, in this system chymotrypsin-like serine proteases are dispensable for high molecular weight DNA fragmentation, however are required for the activation of a relatively small manganese-dependent acidic endonuclease that is responsible for oligonucleosomal fragmentation of DNA. Furthermore, we demonstrate mitochondrial involvement during PBOX-6-induced apoptosis and suggest the existence of unidentified mitochondrial effectors of apoptosis. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
Full text from SpringerLink