Ectopic overexpression of second mitochondria-derived activator of caspases (Smac/DIABLO) or cotreatment with N-terminus of Smac/DIABLO peptide potentiates epothilone B derivative–(BMS 247550) and Apo-2L/TRAIL–induced apoptosis
| Autor: | Ramadevi Nimmanapalli, Shanthi R. Paranawithana, Carlos Fumero, Sylvie Wittman, Hong Gang Wang, Purva Bali, Kapil N. Bhalla, Erica O'Bryan, David Griffin, Fei Guo |
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| Rok vydání: | 2002 |
| Předmět: |
Immunology
Antineoplastic Agents Apoptosis Transfection Caspase 8 Inhibitor of apoptosis Biochemistry Jurkat cells Mitochondrial Proteins TNF-Related Apoptosis-Inducing Ligand Jurkat Cells Survivin Humans Caspase Membrane Glycoproteins biology Caspase 3 Tumor Necrosis Factor-alpha Antimicrotubule agent Intracellular Signaling Peptides and Proteins Drug Synergism Cell Biology Hematology Molecular biology Caspase 9 Peptide Fragments XIAP Thiazoles Epothilones Caspases biology.protein Epoxy Compounds Macrolides biological phenomena cell phenomena and immunity Apoptosis Regulatory Proteins Carrier Proteins BH3 Interacting Domain Death Agonist Protein |
| Zdroj: | Blood. 99:3419-3426 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v99.9.3419 |
| Popis: | Second mitochondria-derived activator of caspases (Smac)/DIABLO is a mitochondrial protein that is released into the cytosol along with cytochrome c (cyt c) during the execution of the intrinsic pathway of apoptosis. Smac/DIABLO promotes apoptosis by neutralizing the inhibitory effect of the inhibitor of apoptosis (IAP) family of proteins on the processing and activities of the effector caspases. Present studies demonstrate that, upon engagement of the mitochondrial pathway of apoptosis, epothilone (Epo) B derivative BMS 247550, a novel nontaxane antimicrotubule agent, as well as the death ligand Apo-2L/TRAIL (tumor necrosis factor-α–related apoptosis-inducing ligand) induce the mitochondrial release and cytosolic accumulation of Smac/DIABLO, along with cyt c, in human acute leukemia Jurkat T cells. While it had no activity alone, ectopic overexpression of Smac/DIABLO or treatment with the N-terminus heptapeptide (Smac-7) or tetrapeptide (Smac-4) of Smac/DIABLO significantly increased Epo B– or Apo-2L/TRAIL–induced processing and PARP cleavage activity of caspase-3. This produced a significant increase in apoptosis of Jurkat cells (P |
| Databáze: | OpenAIRE |
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