Document Detail

Smac-mediated sensitization of human B-lymphoma cells to staurosporine- and lactacystin-triggered apoptosis is apoptosome-dependent.
MedLine Citation:
PMID:  17377587     Owner:  NLM     Status:  MEDLINE    
Second mitochondrial activator of caspase (Smac)-derived peptides have previously been shown to facilitate apoptosis of various types of cancer cells. However, it remains unclear whether the effects of such Smac agonists are dependent on apoptotic protease-activating factor-1 (Apaf-1), a key component of the apoptosome. Here, we explored the role of Apaf-1 through overexpression of this protein in the B-lymphoma cell line Raji that is defective for cytosolic Apaf-1 expression. Enforced expression of Apaf-1 rendered Raji cells sensitive to staurosporine as well as to the proteasome inhibitor, lactacystin. Importantly, co-treatment with Smac peptides resulted in a threefold higher degree of apoptosis in Apaf-1-expressing Raji cells, but not in mock-transfected cells. Smac peptides also potentiated apoptosis of the DG-75 cell line following liberation of endogenous Apaf-1 from the plasma membrane, but were ineffective when added alone. Furthermore, we observed high levels of expression in several B-lymphoma cell lines of cellular inhibitor of apoptosis protein-2 (cIAP2), and immunodepletion of cIAP2 (a target of Smac) was found to sensitize Apaf-1-overexpressing Raji cells to cytochrome c-dependent caspase activation. Collectively, these results demonstrate the importance of Apaf-1 in Smac-mediated potentiation of apoptosis of B-lymphoma-derived cells.
Y Sun; A Ottosson; S Pervaiz; B Fadeel
Related Documents :
10651307 - Resistance to apoptosis induced by microenvironmental stresses is correlated with metas...
11441067 - Chromatin-independent binding of serum amyloid p component to apoptotic cells.
15806977 - Effects of tea constituents on cell cycle progression of human leukemia u937 cells.
11728307 - An epithelial cell destined for apoptosis signals its neighbors to extrude it by an act...
15783087 - Characteristic of two mouse bcr-abl-transformed cell lines: i. general properties of th...
25031317 - Tissue-engineered endometrial model for the study of cell-cell interactions.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-03-22
Journal Detail:
Title:  Leukemia     Volume:  21     ISSN:  0887-6924     ISO Abbreviation:  Leukemia     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-04-25     Completed Date:  2007-06-04     Revised Date:  2013-03-04    
Medline Journal Info:
Nlm Unique ID:  8704895     Medline TA:  Leukemia     Country:  England    
Other Details:
Languages:  eng     Pagination:  1035-43     Citation Subset:  IM    
Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Acetylcysteine / analogs & derivatives*,  pharmacology
Apoptosis / drug effects*
Apoptosomes / physiology*
Apoptotic Protease-Activating Factor 1 / physiology
Caspases / metabolism
Cell Line, Tumor
Inhibitor of Apoptosis Proteins / analysis
Intracellular Signaling Peptides and Proteins / physiology*
Lymphoma, B-Cell / drug therapy,  pathology*
Membrane Microdomains / physiology
Mitochondrial Proteins / physiology*
Staurosporine / pharmacology*
Reg. No./Substance:
0/APAF1 protein, human; 0/Apoptosomes; 0/Apoptotic Protease-Activating Factor 1; 0/BIRC3 protein, human; 0/DIABLO protein, human; 0/Inhibitor of Apoptosis Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/Mitochondrial Proteins; 133343-34-7/lactacystin; 616-91-1/Acetylcysteine; 62996-74-1/Staurosporine; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Thalidomide in newly diagnosed multiple myeloma: influence of thalidomide treatment on peripheral bl...
Next Document:  The quality of molecular response to chemotherapy is predictive for the outcome of AML1-ETO-positive...