Cell Death Differ. 2002 Apr;9(4):439-47.

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

Zhan, Y., Hegde, R., Srinivasula, S. M., Fernandes-Alnemri, T., Alnemri, E. S.,
--- - Center for Apoptosis Research, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA.
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.
PMID: 11965497External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vitro interaction
  DD1 DD2 Reference
Family DD1 DD2 Method Species Region Expression Species Region Expression
DED Caspase8 Link DEDD GST fusion protein pull-down Not specified 1-201 In vitro translation Not specified Full length E.coli 11965497
DED Caspase8 Link DEDD2 GST fusion protein pull-down Not specified 1-201 In vitro translation Not specified Full length E.coli 11965497
DED DEDD Link DEDD GST fusion protein pull-down Not specified Full length E.coli Not specified Full length In vitro translation 11965497
DED DEDD Link DEDD2 GST fusion protein pull-down Not specified Full length E.coli Not specified Full length In vitro translation 11965497
DED DEDD Link DEDD2 GST fusion protein pull-down Not specified Full length In vitro translation Not specified Full length E.coli 11965497
DED DEDD Link FLIP GST fusion protein pull-down Not specified Full length E.coli Human Full length In vitro translation 11965497
DED DEDD2 Link DEDD2 GST fusion protein pull-down Not specified Full length E.coli Not specified Full length In vitro translation 11965497
DED DEDD2 Link FLIP GST fusion protein pull-down Not specified Full length E.coli Human Full length In vitro translation 11965497
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
DED Caspase8 Link DEDD2 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Full length 11965497
DED DEDD Link DEDD2 Co-immunoprecipitation HEK293 Not specified Full length Not specified Full length 11965497
DED DEDD2 Link FLIP Co-Immunofluorescence staining MCF-7 Not specified Full length Not specified Not specified 11965497
DED DEDD2 Link FLIP Co-immunoprecipitation HEK293 Not specified Full length Human Full length 11965497
(Link: click this icon to show interactions only between the two corresponding DDs)