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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Li, Ting Xu, Xuemin Cui, Mei-zhen Zeng, Linlin Fu, Xueqi Gao, Wei |
| Description | Author Affiliation: Li T ( Department of Biomedical and Diagnostic Sciences, University of Tennessee, Knoxville, TN 37996, USA.) |
| Abstract | Presenilin-associated protein (PSAP) has been identified as a mitochondrial proapoptotic protein. However, the mechanism by which PSAP induces apoptosis remains unknown. To this end, we have established an inducible expression system. Using this system, we have examined the roles of B-cell lymphoma 2 (Bcl-2) family proteins, cytochrome c, Smac (Smac/Diablo, second mitochondria-derived activator of caspases/direct IAP binding protein with low PI), and Apaf-1 (apoptotic protease-activating factor) in PSAP-induced apoptosis. Our results demonstrate that knockdown of Apaf-1 abolished PSAP-induced caspase activation and poly(ADP ribose) polymerase (PARP) cleavage, indicating that the apoptosome formation triggered by cytochrome c is crucial for PSAP-induced apoptosis. Our data also demonstrate that knockdown of Smac abolished PSAP-induced caspase activation and PARP cleavage, indicating that, in addition to Apaf-1 or apoptosome formation, Smac is also essential for PSAP-induced apoptosis. However, interestingly, our data demonstrate that overexpression of Bcl-2 and Bcl-xL did not protect cells from PSAP-induced apoptosis, and that knockdown of Bid, Bax, and Bak had no effect on PSAP-induced cytochrome c and Smac release, indicating that PSAP-induced apoptosis is not regulated by Bcl-2 family proteins. These results strongly suggest that PSAP evokes mitochondrial apoptotic cascades via a novel mechanism that is not regulated by Bcl-2 family proteins, but that both the formation of cytochrome c-Apaf-1 apoptosome and the presence of Smac are absolutely required for PSAP-induced apoptosis. |
| ISSN | 00063002 |
| Journal | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer |
| Issue Number | 3 |
| Volume Number | 1832 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2013-03-01 |
| Publisher Place | Netherlands |
| Access Restriction | Open |
| Subject Keyword | Apoptosis Physiology Apoptotic Protease-Activating Factor 1 Metabolism Intracellular Signaling Peptides And Proteins Membrane Proteins Mitochondrial Proteins Signal Transduction Drug Effects Genetics Blotting, Western Caspase 8 Caspase 9 Cytochromes c Flow Cytometry HEK293 Cells Mitochondria Models, Biological Oligopeptides Pharmacology Proto-Oncogene Proteins C-bcl-2 RNA Interference Time Factors Transfection Bcl-2-Associated X Protein Bcl-X Protein Research Support, N.I.H., Extramural Biochemistry |
| Content Type | Text |
| Resource Type | Article |
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