Abstract
The CD95 signaling pathway comprises proteins that contain one or two death effector domains (DED), such as FADD/Mort1 or caspase-8. Here we describe a novel 37 kDa protein, DEDD, that contains an N-terminal DED. DEDD is highly conserved between human and mouse (98.7% identity) and is ubiquitously expressed, Overexpression of DEDD in 293T cells induced weak apoptosis, mainly through its DED by which it interacts with FADD and caspase-8. Endogenous DEDD was found in the cytoplasm and translocated into the nucleus upon stimulation of CD95. Immunocytological studies revealed that overexpressed DEDD directly translocated into the nucleus, where it co-localizes in the nucleolus with UBF, a basal factor required for RNA polymerase I transcription. Consistent with its nuclear localization, DEDD contains two nuclear localization signals and the C-terminal part shares sequence homology with histones. Recombinant DEDD binds to both DNA and reconstituted mononucleosomes and inhibits transcription in a reconstituted in vitro system. The results suggest that DEDD is a final target of a chain of events by which the CD95-induced apoptotic signal is transferred into the nucleolus to shut off cellular biosynthetic activities.
Original language | English (US) |
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Pages (from-to) | 5974-5986 |
Number of pages | 13 |
Journal | EMBO Journal |
Volume | 17 |
Issue number | 20 |
DOIs | |
State | Published - Oct 15 1998 |
Keywords
- Apoptosis
- Death effector domain (DED)
- Mononucleosome
- Nucleolus
- Transcription inhibition
ASJC Scopus subject areas
- General Immunology and Microbiology
- General Biochemistry, Genetics and Molecular Biology
- Molecular Biology
- General Neuroscience