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The contribution of apoptosis-inducing factor, caspase-activated DNase, and inhibitor of caspase-activated DNase to the nuclear phenotype and DNA degradation during apoptosis.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2005 Oct 21; Vol. 280 (42), pp. 35670-83. Date of Electronic Publication: 2005 Jul 27. - Publication Year :
- 2005
-
Abstract
- We have assessed the contribution of apoptosis-inducing factor (AIF) and inhibitor of caspase-activated DNase (ICAD) to the nuclear morphology and DNA degradation pattern in staurosporine-induced apoptosis. Expression of D117E ICAD, a mutant that is resistant to caspase cleavage at residue 117, prevented low molecular weight (LMW) DNA fragmentation, stage II nuclear morphology, and detection of terminal deoxynucleotidyl transferase staining. However, high molecular weight (HMW) DNA fragmentation and stage I nuclear morphology remained unaffected. On the other hand, expression of either D224E or wild type ICAD had no effect on DNA fragmentation or nuclear morphology. In addition, both HMW and LMW DNA degradation required functional executor caspases. Interestingly, silencing of endogenous AIF abolished type I nuclear morphology without any effect on HMW or LMW DNA fragmentation. Together, these results demonstrate that AIF is responsible for stage I nuclear morphology and suggest that HMW DNA degradation is a caspase-activated DNase and AIF-independent process.
- Subjects :
- Apoptosis
Blotting, Western
Cell Line, Tumor
DNA Fragmentation
Deoxyribonucleases chemistry
Dose-Response Relationship, Drug
Enzyme Inhibitors pharmacology
Humans
In Situ Nick-End Labeling
Microscopy, Electron
Microscopy, Fluorescence
Molecular Weight
Mutagenesis
Phenotype
Plasmids metabolism
Staurosporine pharmacology
Transfection
Apoptosis Inducing Factor physiology
Cell Nucleus metabolism
DNA chemistry
Deoxyribonucleases antagonists & inhibitors
Deoxyribonucleases physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 280
- Issue :
- 42
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 16049016
- Full Text :
- https://doi.org/10.1074/jbc.M504015200