Ruggero Davide
School of Medicine and Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California 94158, USA.
Cancer Res. 2009 Dec 1;69(23):8839-43. doi: 10.1158/0008-5472.CAN-09-1970. Epub 2009 Nov 24.
Deregulation in different steps of translational control is an emerging mechanism for cancer formation. One example of an oncogene with a direct role in control of translation is the Myc transcription factor. Myc directly increases protein synthesis rates by controlling the expression of multiple components of the protein synthetic machinery, including ribosomal proteins and initiation factors of translation, Pol III and rDNA. However, the contribution of Myc-dependent increases in protein synthesis toward the multistep process leading to cancer has remained unknown. Recent evidence strongly suggests that Myc oncogenic signaling may monopolize the translational machinery to elicit cooperative effects on cell growth, cell cycle progression, and genome instability as a mechanism for cancer initiation. Moreover, new genetic tools to restore aberrant increases in protein synthesis control are now available, which should enable the dissection of important mechanisms in cancer that rely on the translational machinery.
翻译控制不同步骤中的失调是癌症形成的一种新兴机制。在翻译控制中具有直接作用的一个癌基因实例是Myc转录因子。Myc通过控制蛋白质合成机制的多个组分的表达,包括核糖体蛋白、翻译起始因子、Pol III和rDNA,直接提高蛋白质合成速率。然而,Myc依赖性的蛋白质合成增加对导致癌症的多步骤过程的贡献仍不清楚。最近的证据有力地表明,Myc致癌信号可能垄断翻译机制,以引发对细胞生长、细胞周期进程和基因组不稳定的协同作用,作为癌症起始的一种机制。此外,现在有了恢复蛋白质合成控制异常增加的新遗传工具,这应该能够剖析癌症中依赖翻译机制的重要机制。