DuHadaway J B, Sakamuro D, Ewert D L, Prendergast G C
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Cancer Res. 2001 Apr 1;61(7):3151-6.
The Bin1 gene encodes a c-Myc-interacting adapter protein with tumor suppressor and cell death properties. In this study, we offer evidence that Bin1 participates in a mechanism through which c-Myc activates programmed cell death in transformed primary chick or rat cells. Antisense or dominant inhibitory Bin1 genes did not affect the ability of c-Myc to drive proliferation or transformation, but they did reduce the susceptibility of cells to c-Myc-induced apoptosis. Protein-protein interaction was implicated, suggesting that Bin1 mediates a death or death sensitization signal from c-Myc. Our findings offer direct support for the "dual signal" model of Myc apoptotic function, based on interactions with a binding protein. Loss of Bin1 in human tumors may promote malignant progression in part by helping to stanch the death penalty associated with c-Myc activation.
Bin1基因编码一种具有肿瘤抑制和细胞死亡特性的与c-Myc相互作用的衔接蛋白。在本研究中，我们提供证据表明Bin1参与了一种机制，通过该机制c-Myc在转化的原代鸡或大鼠细胞中激活程序性细胞死亡。反义或显性抑制性Bin1基因不影响c-Myc驱动增殖或转化的能力，但它们确实降低了细胞对c-Myc诱导的凋亡的敏感性。这暗示了蛋白质-蛋白质相互作用，表明Bin1介导来自c-Myc的死亡或死亡致敏信号。我们的发现为基于与结合蛋白相互作用的Myc凋亡功能的“双信号”模型提供了直接支持。人类肿瘤中Bin1的缺失可能部分通过帮助阻止与c-Myc激活相关的死亡惩罚来促进恶性进展。
