Requirement for the CD95 receptor-ligand pathway in c-Myc-induced apoptosis.
Induction of apoptosis by oncogenes like c-myc may be important in restraining the emergence of neoplasia. However, the mechanism by which c-myc induces apoptosis is unknown. CD95 (also termed Fas or APO-1) is a cell surface transmembrane receptor of the tumor necrosis factor receptor family that activates an intrinsic apoptotic suicide program in cells upon binding either its ligand CD95L or antibody. c-myc-induced apoptosis was shown to require interaction on the cell surface between CD95 and its ligand. c-Myc acts downstream of the CD95 receptor by sensitizing cells to the CD95 death signal. Moreover, IGF-I signaling and Bcl-2 suppress c-myc-induced apoptosis by also acting downstream of CD95. These findings link two apoptotic pathways previously thought to be independent and establish the dependency of Myc on CD95 signaling for its killing activity.
Hueber
A O
AO
Imperial Cancer Research Fund (ICRF) Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Zörnig
M
M
Lyon
D
D
Suda
T
T
Nagata
S
S
Evan
G I
GI
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D019898:Autocrine Communication; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D005786:Gene Expression Regulation; D016259:Genes, myc; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000494:pharmacology / Q000502:physiology; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D051381:Rats; D019014:fas Receptor / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C505534:Fadd protein, mouse; C505535:Fadd protein, rat; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; C505658:Fasl protein, mouse; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D019014:fas Receptor; D007334:Insulin-Like Growth Factor I