EMBO J. 1998 Oct 15;17(20):5974-86.

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

Stegh, A. H., Schickling, O., Ehret, A., Scaffidi, C., Peterhansel, C., Hofmann, T. G., Grummt, I., Krammer, P. H., Peter, M. E.,
--- - Tumor Immunology Program, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
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.
PMID: 9774341External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vitro interaction
  DD1 DD2 Reference
Family DD1 DD2 Method Species Region Expression Species Region Expression
DED Caspase8 Link DEDD GST fusion protein pull-down Not specified Full length In vitro translation Human 1-318 In vitro translation 9774341
DED Caspase8 Link DEDD GST fusion protein pull-down Not specified 1-180 In vitro translation Human 1-318 In vitro translation 9774341
DED DEDD Link FADD GST fusion protein pull-down Human 1-318 In vitro translation Not specified Full length In vitro translation 9774341
DED DEDD Link FADD GST fusion protein pull-down Human 1-318 In vitro translation Not specified 1-88 In vitro translation 9774341
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
DED Caspase8 Link DEDD Co-immunoprecipitation HEK293 Not used Human 1-318 9774341
DED DEDD Link FADD Co-immunoprecipitation HEK293 Human 1-318 Not used 9774341
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Functional Role
Family DD1 DD2 Method Death-related Death-unrelated Reference
DED DEDD Link FADD Data not shown Apoptosis 9774341
(Link: click this icon to show interactions only between the two corresponding DDs)