Identification and characterization of DEDDL, a human-specific isoform of DEDD.
Death effector domain (DED) containing molecules are usually involved in the intracellular apoptosis cascade as executioners or regulators. One of these molecules, DEDD, was identified as a final target of the CD95 signaling pathway by which it would be transferred into the nucleolus to inhibit RNA polymerase I-dependent transcription. Here we describe a longer isoform of DEDD, DEDDL, produced by alternatively splicing, as an immune cell-specific DED-containing molecule. It is only expressed in human T lymphocytes and dendritic cells (DCs), and the mRNA expression in DCs was elevated upon inductive maturation. In cell lines MCF-7 and Jurkat, the overexpression of DEDDL could induce apoptosis more potently than that of DEDD. That DEDDL could bind FADD and cFLIP more potently than DEDD in vivo was revealed by cotransfection and immunoprecipitation. This may explain why DEDDL is a more potent apoptosis inducer, because DED-containing proteins usually induce apoptosis through DED binding. Finally, why DEDD and DEDDL are unstable in the overexpression and other studies may be explained by the finding that they are potential substrates of active caspases.
Huang
Xin
X
Institute of Immunology, Second Military Medical University, Shanghai, 200433, PR China. xhuang@lifespan.org
Zhang
Minghui
M
Tang
Hua
H
Ruo
Chunfang
C
Cao
Xuetao
X
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D017209:Apoptosis; D001483:Base Sequence; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism*; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D019169:Jurkat Cells / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000378:metabolism*; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; C116096:DEDD protein, human; D004268:DNA-Binding Proteins; D053418:Death Domain Receptor Signaling Adaptor Proteins; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D020033:Protein Isoforms; D012333:RNA, Messenger; C434062:TNIP2 protein, human; D020169:Caspases