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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Schickling, Olaf Oshima, Robert G. Stegh, Alexander H. Dinsdale, David Peter, Marcus E. Cohen, Gerald M. Lee, Justine C. |
| Description | Author Affiliation: Lee JC ( The Ben May Institute for Cancer Research, University of Chicago, 924 E 57th Street, Chicago, IL 60637, USA.) |
| Abstract | Apoptosis depends critically on regulated cytoskeletal reorganization events in a cell. We demonstrate that death effector domain containing DNA binding protein (DEDD), a highly conserved and ubiquitous death effector domain containing protein, exists predominantly as mono- or diubiquitinated, and that diubiquitinated DEDD interacts with both the K8/18 intermediate filament network and pro–caspase-3. Early in apoptosis, both cytosolic DEDD and its close homologue DEDD2 formed filaments that colocalized with and depended on K8/18 and active caspase-3. Subsequently, these filamentous structures collapsed into intracellular inclusions that migrated into cytoplasmic blebs and contained DEDD, DEDD2, active caspase-3, and caspase-3–cleaved K18 late in apoptosis. Biochemical studies further confirmed that DEDD coimmunoprecipitated with both K18 and pro–caspase-3, and kinetic analyses placed apoptotic DEDD staining prior to caspase-3 activation and K18 cleavage. In addition, both caspase-3 activation and K18 cleavage was inhibited by expression of DEDDΔNLS1-3, a cytosolic form of DEDD that cannot be ubiquitinated. Finally, siRNA mediated DEDD knockdown cells exhibited inhibition of staurosporine-induced DNA degradation. Our data suggest that DEDD represents a novel scaffold protein that directs the effector caspase-3 to certain substrates facilitating their ordered degradation during apoptosis. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 6 |
| Volume Number | 158 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 2002-09-16 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Apoptosis DNA-Binding Proteins Physiology Intermediate Filaments Metabolism Intracellular Signaling Peptides And Proteins Animals Apoptosis Regulatory Proteins Carrier Proteins Caspase 3 Caspases DNA Death Domain Receptor Signaling Adaptor Proteins Enzyme Inhibitors Pharmacology Enzyme Precursors HeLa Cells Inclusion Bodies Chemistry Ultrastructure Jurkat Cells Keratins Kinetics Membrane Glycoproteins Mice Mice, Inbred C3H Mice, Inbred C57BL Nuclear Proteins RNA, Small Interfering RNA, Untranslated Staurosporine TNF-Related Apoptosis-Inducing Ligand Tumor Cells, Cultured Tumor Necrosis Factor-alpha Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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