Hueber A O, Zörnig M, Lyon D, Suda T, Nagata S, Evan G I
Imperial Cancer Research Fund (ICRF) Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Science. 1997 Nov 14;278(5341):1305-9. doi: 10.1126/science.278.5341.1305.
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.
像c-myc这样的癌基因诱导细胞凋亡可能在抑制肿瘤形成过程中起重要作用。然而，c-myc诱导细胞凋亡的机制尚不清楚。CD95（也称为Fas或APO-1）是肿瘤坏死因子受体家族的一种细胞表面跨膜受体，当其与配体CD95L或抗体结合时，可激活细胞内的固有凋亡自杀程序。研究表明，c-myc诱导的细胞凋亡需要CD95与其配体在细胞表面相互作用。c-Myc通过使细胞对CD95死亡信号敏感而在CD95受体的下游发挥作用。此外，IGF-I信号传导和Bcl-2也通过在CD95下游发挥作用来抑制c-myc诱导的细胞凋亡。这些发现将两条先前被认为是独立的凋亡途径联系起来，并确立了Myc的杀伤活性对CD95信号传导的依赖性。
