Nuclear and cytoplasmic shuttling of TRADD induces apoptosis via different mechanisms Journal Article
| Authors: | Morgan, M.; Thorburn, J.; Pandolfi, P. P.; Thorburn, A. |
| Article Title: | Nuclear and cytoplasmic shuttling of TRADD induces apoptosis via different mechanisms |
| Abstract: | The adapter protein tumor necrosis factor receptor (TNFR)1-associated death domain (TRADD) plays an essential role in recruiting signaling molecules to the TNFRI receptor complex at the cell membrane. Here we show that TRADD contains a nuclear export and import sequence that allow shuttling between the nucleus and the cytoplasm. In the absence of export, TRADD is found within nuclear structures that are associated with promyelocytic leukemia protein (PML) nuclear bodies. In these structures, the TRADD death domain (TRADD-DD) can activate an apoptosis pathway that is mechanistically distinct from its action at the membrane-bound TNFR1 complex. Apoptosis by nuclear TRADD-DD is promyelocytic leukemia protein dependent, involves p53, and is inhibited by Bcl-xL but not by caspase inhibitors or dominant negative FADD (FADD-DN). Conversely, apoptosis induced by TRADD in the cytoplasm is resistant to Bcl-xL, but sensitive to caspase inhibitors and FADD-DN. These data indicate that nucleocytoplasmic shuttling of TRADD leads to the activation of distinct apoptosis mechanisms that connect the death receptor apparatus to nuclear events. |
| Keywords: | signal transduction; controlled study; unclassified drug; human cell; proteins; animals; mice; mice, knockout; apoptosis; cell protein; tumor cells, cultured; caspase inhibitor; protein bcl xl; protein p53; amino acid sequence; molecular sequence data; sequence alignment; cell membrane; promyelocytic leukemia; tumor suppressor protein p53; cytoplasm; cell nucleus; protein structure; p53; receptors, tumor necrosis factor; leptomycin b; adaptor protein; pml; cell nucleus inclusion body; fatty acids, unsaturated; tumor necrosis factor receptor-associated peptides and proteins; humans; human; female; priority journal; article; tradd; protein tradd; tnf receptor-associated death domain protein; tnf receptor-associated factor 1 |
| Journal Title: | Journal of Cell Biology |
| Volume: | 157 |
| Issue: | 6 |
| ISSN: | 0021-9525 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2002-06-10 |
| Start Page: | 975 |
| End Page: | 984 |
| Language: | English |
| DOI: | 10.1083/jcb.200204039 |
| PUBMED: | 12045187 |
| PROVIDER: | scopus |
| PMCID: | PMC2174032 |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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