Death effector domain-containing proteins DEDD and FLAME-3 form nuclear complexes with the TFIIIC102 subunit of human transcription factor IIIC

Cell Death Differ. 2002 Apr;9(4):439-47. doi: 10.1038/sj.cdd.4401038.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Nucleus / metabolism*
  • Cells, Cultured
  • Cloning, Molecular
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Death Domain Receptor Signaling Adaptor Proteins
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Macromolecular Substances
  • Mice
  • Molecular Sequence Data
  • NF-kappa B / antagonists & inhibitors
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Sequence Analysis
  • Sequence Analysis, Protein
  • Transcription Factors, TFIII / genetics
  • Transcription Factors, TFIII / metabolism*
  • Transfection

Substances

  • Carrier Proteins
  • DEDD protein, human
  • DEDD2 protein, human
  • DNA-Binding Proteins
  • Death Domain Receptor Signaling Adaptor Proteins
  • Dedd protein, mouse
  • GTF3C3 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Macromolecular Substances
  • NF-kappa B
  • Nuclear Proteins
  • Transcription Factors, TFIII
  • transcription factor TFIIIC

Associated data

  • GENBANK/AF457575
  • GENBANK/AF457576
  • GENBANK/AF465407