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

108 Citations (Scopus)

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

Fingerprint

Death Domain Receptor Signaling Adaptor Proteins
Caspase 8
Transcription
RNA Polymerase I
Pol1 Transcription Initiation Complex Proteins
Histones
Nuclear Localization Signals
Proteins
HEK293 Cells
Apoptosis
Sequence Homology
DNA
Cytoplasm
Death Effector Domain

Keywords

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

ASJC Scopus subject areas

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

Cite this

Stegh, Alexander H. ; Schickling, Olaf ; Ehret, Andreas ; Scaffidi, Carsten ; Peterhänsel, Christoph ; Hofmann, Thomas G. ; Grummt, Ingrid ; Krammer, Peter H. ; Peter, Marcus E. / DEDD, a novel death effector domain-containing protein, targeted to the nucleolus. In: EMBO Journal. 1998 ; Vol. 17, No. 20. pp. 5974-5986.
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Stegh, AH, Schickling, O, Ehret, A, Scaffidi, C, Peterhänsel, C, Hofmann, TG, Grummt, I, Krammer, PH & Peter, ME 1998, 'DEDD, a novel death effector domain-containing protein, targeted to the nucleolus', EMBO Journal, vol. 17, no. 20, pp. 5974-5986. https://doi.org/10.1093/emboj/17.20.5974

DEDD, a novel death effector domain-containing protein, targeted to the nucleolus. / Stegh, Alexander H.; Schickling, Olaf; Ehret, Andreas; Scaffidi, Carsten; Peterhänsel, Christoph; Hofmann, Thomas G.; Grummt, Ingrid; Krammer, Peter H.; Peter, Marcus E.

In: EMBO Journal, Vol. 17, No. 20, 15.10.1998, p. 5974-5986.

Research output: Contribution to journalArticle

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T1 - DEDD, a novel death effector domain-containing protein, targeted to the nucleolus

AU - Stegh, Alexander H.

AU - Schickling, Olaf

AU - Ehret, Andreas

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AU - Peterhänsel, Christoph

AU - Hofmann, Thomas G.

AU - Grummt, Ingrid

AU - Krammer, Peter H.

AU - Peter, Marcus E.

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N2 - 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.

AB - 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.

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Stegh AH, Schickling O, Ehret A, Scaffidi C, Peterhänsel C, Hofmann TG et al. DEDD, a novel death effector domain-containing protein, targeted to the nucleolus. EMBO Journal. 1998 Oct 15;17(20):5974-5986. https://doi.org/10.1093/emboj/17.20.5974