Interaction of Fas(Apo-1/CD95) with proteins implicated in the ubiquitination pathway.
Fas(Apo-1/CD95), a receptor belonging to the tumor necrosis factor receptor family, induces apoptosis when triggered by Fas ligand. Upon its activation, the cytoplasmic domain of Fas binds several proteins which transmit the death signal. We used the yeast two-hybrid screen to isolate Fas-associated proteins. Here we report that the ubiquitin-conjugating enzyme UBC9 binds to Fas at the interface between the death domain and the membrane-proximal region of Fas. This interaction is also seen in vivo. UBC9 transiently expressed in HeLa cells bound to the co-expressed cytoplasmic segment of Fas. FAF1, a Fas-associated protein that potentiates apoptosis (Chu et al. (1996) Proc. Natl. Acad. Sci. USA 92, 11894-11898), was found to contain sequences similar to ubiquitin. These results suggest that proteins related to the ubiquitination pathway may modulate the Fas signaling pathway.
Becker
K
K
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Schneider
P
P
Hofmann
K
K
Mattmann
C
C
Tschopp
J
J
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008025:Ligases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D017385:Sequence Homology; D015398:Signal Transduction; D014162:Transfection; D044763:Ubiquitin-Conjugating Enzymes; D014452:Ubiquitins / Q000737:chemistry / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C490780:FAF1 protein, human; C097186:Faf1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D014452:Ubiquitins; D019014:fas Receptor; D044763:Ubiquitin-Conjugating Enzymes; D008025:Ligases; D000098843:Ubiquitin-Conjugating Enzyme UBC9