Oncogene. 2003 Jan 16;22(2):291-7.

DEDD and DEDD2 associate with caspase-8/10 and signal cell death.External

Alcivar, A., Hu, S., Tang, J., Yang, X.,
--- - Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
An apoptotic signal triggered by cell surface death receptors is disseminated to intracellular compartments through protein-protein interactions mediated by conserved domains such as the death effector domain (DED). A unique family of single DED-containing proteins, including DEDD and DEDD2, is targeted to the nucleolus. However, the role of DEDD/DEDD2 in apoptosis remains less understood. Here we show that DEDD and DEDD2 are highly conserved in diverse species, and that they are potent inducers of apoptosis in various cell types. Deletion analysis indicates that both the N-terminal DED domain and the C-terminal region of DEDD2 can induce apoptosis. The cell death activity of this family appears to be related to their nuclear localization. DEDD and DEDD2 bind to two tandem DED-containing caspases, caspase -8 and -10, that are engaged by death receptors. Consistent with the nuclear localization of this family, caspase-8 translocates to the nucleus during CD95-induced apoptosis. DEDD and DEDD2 also readily associate with themselves and with each other. These results suggest that DEDD and DEDD2 may be important mediators for death receptors and that they may target caspases to the nucleus.
PMID: 12527898External
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 DEDD Link DEDD2 GST fusion protein pull-down Not specified Not specified In vitro translation Not specified 1-115 E.coli 12527898
(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 Caspase10 Link DEDD2 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Full length 12527898
DED Caspase8 Link DEDD2 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Full length 12527898
DED Caspase8 Link DEDD2 Co-immunoprecipitation HEK293 Not specified Not specified Not specified 1-115 12527898
DED DEDD Link DEDD Co-immunoprecipitation HEK293 Not specified Not specified Not specified Not specified 12527898
DED DEDD Link DEDD2 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Full length 12527898
DED DEDD Link DEDD2 Co-immunoprecipitation HEK293 Not specified Not specified Not specified 1-115 12527898
DED DEDD Link DEDD2 Co-immunoprecipitation HEK293 Not specified Full length Not specified Full length 12527898
DED DEDD Link DEDD2 Co-immunoprecipitation HEK293 Not specified Full length Not specified 1-115 12527898
DED DEDD2 Link DEDD2 Co-immunoprecipitation HEK293 Not specified Full length Not specified Full length 12527898
DED DEDD2 Link DEDD2 Co-immunoprecipitation HEK293 Not specified Full length Not specified 1-115 12527898
(Link: click this icon to show interactions only between the two corresponding DDs)