DEDD, a novel death effector domain-containing protein, targeted to the nucleolus

Alexander H. Stegh, Olaf Schickling, Andreas Ehret, Carsten Scaffidi, Christoph Peterhänsel, Thomas G. Hofmann, Ingrid Grummt, Peter H. Krammer, Marcus E. Peter*

*Corresponding author for this work

Research output: Contribution to journalArticle

109 Scopus citations

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 languageEnglish (US)
Pages (from-to)5974-5986
Number of pages13
JournalEMBO Journal
Volume17
Issue number20
DOIs
StatePublished - Oct 15 1998

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Keywords

  • Apoptosis
  • Death effector domain (DED)
  • Mononucleosome
  • Nucleolus
  • Transcription inhibition

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Stegh, A. H., Schickling, O., Ehret, A., Scaffidi, C., Peterhänsel, C., Hofmann, T. G., Grummt, I., Krammer, P. H., & Peter, M. E. (1998). DEDD, a novel death effector domain-containing protein, targeted to the nucleolus. EMBO Journal, 17(20), 5974-5986. https://doi.org/10.1093/emboj/17.20.5974