Abstract |
Smac/DIABLO, a proapoptotic protein released from mitochondrial intermembrane space during apoptosis, promotes caspases activation by IAPs neutralization. The kinetics and molecular mechanism of Smac/DIABLO release from mitochondria has remained obscure. Present study is focused on the role of Bid in the control of Bax-GFP and Smac/DIABLO-GFP kinetics in breast cancer MCF-7 cells stimulated to apoptosis with camptothecin ( CPT). Minute kinetics of proteins was examined by homeostatic confocal microscopy. The release of Smac/DIABLO-GFP from mitochondria comprised two phases: initial-rapid, lasting 20-30 min and subsequent 30 min-plateau phase, followed by the decrease of Smac/DIABLO-related fluorescence due to cell destruction. The kinetics of Bax-GFP aggregation on mitochondria coincided in time with Smac/DIABLO-GFP release from these organelles. Bid knock down and Bcl-2 overexpression delayed Bax-GFP aggregation and completely inhibited Smac/DIABLO-GFP release from mitochondria. Knock down of caspase 8 (activator of Bid) delayed both Bax-GFP aggregation and Smac/DIABLO-GFP release in CPT-treated cells. In conclusion, Bid protein is crucial for the control of the release of Smac/DIABLO from mitochondria in breast cancer MCF-7 stimulated to apoptosis with CPT.
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Authors | M Górka, M Lamparska-Przybysz, T Motyl |
Journal | Cellular and molecular biology (Noisy-le-Grand, France)
(Cell Mol Biol (Noisy-le-grand))
Vol. 52 Suppl
Pg. OL915-22
(Jan 21 2007)
ISSN: 1165-158X [Electronic] France |
PMID | 17666167
(Publication Type: Journal Article)
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Chemical References |
- Apoptosis Regulatory Proteins
- BH3 Interacting Domain Death Agonist Protein
- DIABLO protein, human
- Enzyme Inhibitors
- Intracellular Signaling Peptides and Proteins
- Mitochondrial Proteins
- bcl-2-Associated X Protein
- Green Fluorescent Proteins
- Caspase 8
- Camptothecin
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Topics |
- Apoptosis
(drug effects)
- Apoptosis Regulatory Proteins
- BH3 Interacting Domain Death Agonist Protein
(genetics, metabolism)
- Breast Neoplasms
(metabolism, pathology)
- Camptothecin
(pharmacology)
- Caspase 8
(metabolism)
- Cell Line, Tumor
- Enzyme Inhibitors
(pharmacology)
- Female
- Green Fluorescent Proteins
(metabolism)
- Humans
- Intracellular Signaling Peptides and Proteins
(antagonists & inhibitors, metabolism)
- Kinetics
- Mitochondrial Proteins
(antagonists & inhibitors, metabolism)
- bcl-2-Associated X Protein
(metabolism)
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