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| Content Provider | PubMed Central |
|---|---|
| Author | Hamid, Kashkar Haefs, Christiane Shin, Hwain Hamilton-dutoit, Stephen J. Salvesen, Guy S. Martin, Krönke Jürgensmeier, Juliane M. |
| Copyright Year | 2003 |
| Abstract | The malignant Hodgkin and Reed-Sternberg cells of Hodgkin's lymphoma (HL) and HL-derived B cell lines were previously shown to be resistant to different apoptotic stimuli. We show here that cytochrome c fails to stimulate caspases-9 and -3 activation in cytosolic extracts of HL-derived B cells, which is due to high level expression of X-linked inhibitor of apoptosis (XIAP). Coimmunoprecipitation studies revealed that XIAP, apoptosis protease-activating factor–1, and caspase-3 are complexed in HL-derived B cell lysates. Even after stimulation with exogenous cytochrome c and dATP, XIAP impairs the proteolytic processing and activation of caspase-3. In cytosolic extracts, inhibition of XIAP by the second mitochondria-derived activator of caspases (Smac)/DIABLO, or immunodepletion of XIAP restores cytochrome c–triggered processing and activation of caspase-3. Smac or a Smac-derived agonistic peptide also sensitized intact HL-derived B cells for the apoptotic action of staurosporine. Finally, Hodgkin and Reed-Sternberg cells of primary tumor HL tissues also constitutively and abundantly express XIAP. The results of this paper suggest that high level XIAP expression is a hallmark of HL, which may play a crucial role in resistance to apoptosis. |
| Related Links | http://dx.doi.org/10.1084/jem.20021279 |
| Ending Page | 347 |
| Page Count | 7 |
| Starting Page | 341 |
| File Format | |
| ISSN | 00221007 |
| e-ISSN | 15409538 |
| Journal | The Journal of Experimental Medicine |
| Issue Number | 2 |
| Volume Number | 198 |
| Language | English |
| Publisher | The Rockefeller University Press |
| Publisher Date | 2003-07-21 |
| Access Restriction | Open |
| Rights Holder | The Rockefeller University Press |
| Subject Keyword | Immunology Immunology and Allergy Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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