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PMID:11741985

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Citation

Roth, W, Stenner-Liewen, F, Pawlowski, K, Godzik, A and Reed, JC (2002) Identification and characterization of DEDD2, a death effector domain-containing protein. J. Biol. Chem. 277:7501-8

Abstract

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.

Links

PubMed Online version:10.1074/jbc.M110749200

Keywords

Active Transport, Cell Nucleus; Amino Acid Sequence; Animals; Antigens, CD95/metabolism; Apoptosis; Arabidopsis Proteins; Blotting, Northern; CASP8 and FADD-Like Apoptosis Regulating Protein; COS Cells; Carrier Proteins/biosynthesis; Carrier Proteins/chemistry; Carrier Proteins/metabolism; Caspase 8; Caspase 9; Caspases/metabolism; Cell Line; Cell Nucleus/metabolism; Cloning, Molecular; Cytosol/metabolism; DNA/metabolism; DNA, Complementary/metabolism; DNA-Binding Proteins/chemistry; Death Domain Receptor Signaling Adaptor Proteins; Expressed Sequence Tags; Fatty Acid Desaturases/metabolism; Humans; Intracellular Signaling Peptides and Proteins; Microscopy, Fluorescence; Molecular Sequence Data; Nuclear Proteins/biosynthesis; Nuclear Proteins/chemistry; Plasmids/metabolism; Precipitin Tests; Protein Binding; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-bcl-2; RNA, Messenger/metabolism; Reverse Transcriptase Polymerase Chain Reaction; Sequence Homology, Amino Acid; Time Factors; Tissue Distribution; bcl-2-Associated X Protein

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:CFLAR

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8WXF8

F

Seeded From UniProt

complete

HUMAN:DEDD2

enables

GO:0030159: signaling receptor complex adaptor activity

ECO:0000303: author statement without traceable support used in manual assertion

F

Seeded From UniProt

complete

HUMAN:DEDD2

located_in

GO:0005730: nucleolus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:DEDD2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O15519

F

Seeded From UniProt

complete

HUMAN:DEDD2

GO:0006915: apoptotic process

ECO:0000316:

P

Fig 4 shows that DEDD2 is able to induce apoptosis

Missing: with/from
CACAO 5249

HUMAN:DEDD2

part_of

GO:0005730: nucleolus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:DEDD2

involved_in

GO:0006396: RNA processing

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

HUMAN:DEDD2

involved_in

GO:0008625: extrinsic apoptotic signaling pathway via death domain receptors

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:DEDD2

involved_in

GO:0019725: cellular homeostasis

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

HUMAN:DEDD2

involved_in

GO:0016075: rRNA catabolic process

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

HUMAN:DEDD2

enables

GO:0030159: receptor signaling complex adaptor activity

ECO:0000303: author statement without traceable support used in manual assertion

F

Seeded From UniProt

complete

HUMAN:DEDD2

involved_in

GO:0030262: apoptotic nuclear changes

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:DEDD2

involved_in

GO:0035556: intracellular signal transduction

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

HUMAN:DEDD2

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

HUMAN:DEDD2

involved_in

GO:2001238: positive regulation of extrinsic apoptotic signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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