Identification and characterization of DEDD2, a death effector domain-containing protein.
A novel Death Effector Domain-containing protein was identified, DEDD2, which is closest in amino acid sequence homology to death effector domain-containing DNA-binding protein, DEDD. DEDD2 mRNA is expressed widely in adult human tissues with highest levels in liver, kidney, and peripheral blood leukocytes. DEDD2 interacts with FLIP, but not with Fas-associated death domain (FADD) or caspase-8. Overexpression of DEDD2 induces moderate apoptosis and results in substantial sensitization to apoptosis induced by Fas (CD95/APO-1), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, Apo2L), or FADD. In contrast, Bax- or staurosporine-mediated cell death is not affected by expression of DEDD2. Fluorescence microscopy showed that overexpressed DEDD2 translocates to the nucleus, which is dependent on the presence of a bipartite nuclear localization signal in the DEDD2 protein. Mutagenesis studies revealed that the translocation of the DED of DEDD2 to the nucleus is essential for its pro-apoptotic activity. These findings suggest that DEDD2 is involved in the regulation of nuclear events mediated by the extrinsic apoptosis pathway.
Pubmed ID: 11741985 RIS Download
Active Transport, Cell Nucleus | Amino Acid Sequence | Animals | Antigens, CD95 | Apoptosis | Arabidopsis Proteins | Blotting, Northern | CASP8 and FADD-Like Apoptosis Regulating Protein | COS Cells | Carrier Proteins | Caspase 8 | Caspase 9 | Caspases | Cell Line | Cell Nucleus | Cloning, Molecular | Cytosol | DNA | DNA, Complementary | DNA-Binding Proteins | Death Domain Receptor Signaling Adaptor Proteins | Expressed Sequence Tags | Fatty Acid Desaturases | Humans | Intracellular Signaling Peptides and Proteins | Microscopy, Fluorescence | Molecular Sequence Data | Nuclear Proteins | Plasmids | Precipitin Tests | Protein Binding | Proto-Oncogene Proteins | Proto-Oncogene Proteins c-bcl-2 | RNA, Messenger | Reverse Transcriptase Polymerase Chain Reaction | Sequence Homology, Amino Acid | Time Factors | Tissue Distribution | bcl-2-Associated X Protein