Death effector domain-containing proteins DEDD and FLAME-3 form nuclear complexes with the TFIIIC102 subunit of human transcription factor IIIC.
Death effector domain-containing proteins are involved in important cellular processes such as death-receptor induced apoptosis, NF-kappaB activation and ERK activation. Here we report the identification of a novel nuclear DED-containing protein, FLAME-3. FLAME-3 shares significant sequence (46.6% identical) and structural homology to another DED-containing protein, DEDD. FLAME-3 interacts with DEDD ... and c-FLIP (FLAME-1) but not with the other DED-containing proteins FADD, caspase-8 or caspase-10. FLAME-3 translocates to, and sequesters c-FLIP in the nucleus upon overexpression in human cell lines. Using the yeast two-hybrid system to identify DEDD-interacting proteins, the TFIIIC102 subunit of human transcription factor TFIIIC was identified as a DEDD- and FLAME-3-specific interacting protein. Co-expression of either DEDD or FLAME-3 with hTFIIIC102 in MCF-7 cells induces the translocation from the cytoplasm and sequestration of hTFIIIC102 in the nucleus, indicating that DEDD and FLAME-3 form strong heterocomplexes with hTFIIIC102 and might be important regulators of the activity of the hTFIIIC transcriptional complex. Consistent with this, overexpression of DEDD or FLAME-3 in 293 cells inhibited the expression of a luciferase-reporter gene under the control of the NF-kappaB promoter. Our data provide the first direct evidence for the involvement of DED-containing proteins in the regulation of components of the general transcription machinery in the nucleus.
Mesh Terms:
Amino Acid Sequence, Animals, Carrier Proteins, Cell Nucleus, Cells, Cultured, Cloning, Molecular, DNA-Binding Proteins, Death Domain Receptor Signaling Adaptor Proteins, Humans, Intracellular Signaling Peptides and Proteins, Macromolecular Substances, Mice, Molecular Sequence Data, NF-kappa B, Nuclear Proteins, Protein Structure, Tertiary, Sequence Alignment, Sequence Analysis, Sequence Analysis, Protein, Transcription Factors, TFIII, Transfection
Amino Acid Sequence, Animals, Carrier Proteins, Cell Nucleus, Cells, Cultured, Cloning, Molecular, DNA-Binding Proteins, Death Domain Receptor Signaling Adaptor Proteins, Humans, Intracellular Signaling Peptides and Proteins, Macromolecular Substances, Mice, Molecular Sequence Data, NF-kappa B, Nuclear Proteins, Protein Structure, Tertiary, Sequence Alignment, Sequence Analysis, Sequence Analysis, Protein, Transcription Factors, TFIII, Transfection
Cell Death Differ.
Date: Apr. 01, 2002
PubMed ID: 11965497
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