A novel protein that interacts with the death domain of Fas/APO1 contains a sequence motif related to the death domain.
Signaling for cell death by Fas/APO1 occurs via a distinct region in its intracellular domain. This region contains a conserved sequence motif, the death domain motif, that is also found in the intracellular domains of the p55 tumor necrosis factor receptor and the low affinity nerve growth factor receptor, as well as in the regulatory domain of the ankyrins. A novel protein that specifically binds to the death domain of Fas/APO1 but not to Fas/APO1 molecules with a loss of function point mutation occurring in lprcg mice was cloned by a two-hybrid screen of a HeLa cells' cDNA library. The cloned protein itself contains a death domain motif, and this region binds to the death domain of Fas/APO1, while the region upstream to the death domain prompts self-association of the protein. Induced expression of the protein results in ligand-independent triggering of cytotoxicity, suggesting that it is involved in cell death induction by Fas/APO1.
Boldin
M P
MP
Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot, Israel.
Varfolomeev
E E
EE
Pancer
Z
Z
Mett
I L
IL
Camonis
J H
JH
Wallach
D
D
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D018076:DNA, Complementary; D053200:Fas-Associated Death Domain Protein; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011506:Proteins / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D019014:fas Receptor
D048868:Adaptor Proteins, Signal Transducing; D000954:Antigens, Surface; D002352:Carrier Proteins; D018076:DNA, Complementary; C505533:FADD protein, human; C505534:Fadd protein, mouse; D053200:Fas-Associated Death Domain Protein; D011506:Proteins; D019014:fas Receptor