Interaction of caspase-3 and caspase-9 with the intracytoplasmic
domain of DCC. (A) Two-hybrid screening of DCC-IC
revealed interaction with caspase-3. Y190 yeast transformed with a GAL4
DNA binding domain-DCC-IC fusion (DCC) were transformed with
either a mock plasmid containing the GAL4 transcriptional activation
domain AD (DCC + vector) or a similar construct fused to a brain
cDNA library. Cells were then allowed to grow in the absence of
leucine, tryptophan, and histidine and in the presence of 55 mM
3-amino-1,2,4-triazole. The clone corresponding to caspase-3 is shown
(DCC + caspase-3). (B) Coimmunoprecipitations were
performed on 293T cells cotransfected with pcDNA-DNcasp3 (casp.3) or
pcDNA-3 (cont.) and pDCC-CMV-S, pDCC-CMV.D1290N, or pDCC-CMV-S +
pGNET1myc, the netrin-1-encoding plasmid. To obtain a similar
expression of the protein DCC in the different sample, half of the
plasmid pDCC-CMV-S was used when cotransfected with the
netrin-1-expressing vector because the presence of DCC ligand leads to
increased stability of DCC (13). Anti-caspase-3 antibody was used to
immunoprecipitate caspase-3, and binding was revealed by Western blot
by using anti-DCC antibody. (C) Same as in
B except that pcDNA-DNcasp9 and pcDNA-DNcasp6 were used.
In this case, anti-Flag antibody was used to immunoprecipitate
DNcaspase-9 and DNcaspase-6. (D) Immunoprecipitation of
DCC by caspase-9 was performed by using IMR-32 cells. The pull-down was
performed with or without anti-caspase-9 antibody. (E)
Coimmunoprecipitations were performed, respectively, as in
B and C on 293T cotransfected with
pcDNA-DNcasp3 or pcDNA-DNcasp9 in the presence of either
pDCC-CMV-Δ1121–1290 or pDCC-CMV-Δ1290–1447. tot., immunoblots
performed on the lysate before addition of the antibodies allowing the
pull out; IP, immunoblots by using an anti-DCC antibody on samples
derived from the pull-downs. In B–E, dominant negative
mutants of caspases were chosen instead of tagged wild-type because
overexpression of wild-type caspase drove massive 293T cell death.