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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

Authors

  • Roth W
  • Stenner-Liewen F
  • Pawlowski K
  • Godzik A
  • Reed JC

Journal

The Journal of biological chemistry

Publication Data

March 1, 2002

Associated Grants

  • Agency: NCI NIH HHS, Id: CA 69381
  • Agency: NIGMS NIH HHS, Id: GM 60554

Mesh Terms

  • 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