DEDD, a novel death effector domain-containing protein, targeted to the nucleolus.
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.
Stegh
A H
AH
Tumor Immunology Program, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Schickling
O
O
Ehret
A
A
Scaffidi
C
C
Peterhänsel
C
C
Hofmann
T G
TG
Grummt
I
I
Krammer
P H
PH
Peter
M E
ME
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D029681:Arabidopsis Proteins; D001483:Base Sequence; D002466:Cell Nucleolus / Q000378:metabolism*; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D053418:Death Domain Receptor Signaling Adaptor Proteins; D044943:Fatty Acid Desaturases / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D008223:Lymphoma; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism*; D010940:Plant Proteins / Q000378:metabolism; D011485:Protein Binding; D014407:Tumor Cells, Cultured
D029681:Arabidopsis Proteins; C116096:DEDD protein, human; D004268:DNA-Binding Proteins; D053418:Death Domain Receptor Signaling Adaptor Proteins; C486432:Dedd protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D010940:Plant Proteins; D044943:Fatty Acid Desaturases; C084083:Fad7 protein, Arabidopsis