Jeong Seung Min, Haigis Marcia C
Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
Institute for Aging and Metabolic Diseases, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
Mol Cells. 2015 Sep;38(9):750-8. doi: 10.14348/molcells.2015.0167. Epub 2015 Sep 18.
Genomic instability and altered metabolism are key features of most cancers. Recent studies suggest that metabolic reprogramming is part of a systematic response to cellular DNA damage. Thus, defining the molecules that fine-tune metabolism in response to DNA damage will enhance our understanding of molecular mechanisms of tumorigenesis and have profound implications for the development of strategies for cancer therapy. Sirtuins have been established as critical regulators in cellular homeostasis and physiology. Here, we review the emerging data revealing a pivotal function of sirtuins in genome maintenance and cell metabolism, and highlight current advances about the phenotypic consequences of defects in these critical regulators in tumorigenesis. While many questions should be addressed about the regulation and context-dependent functions of sirtuins, it appears clear that sirtuins may provide a promising, exciting new avenue for cancer therapy.
基因组不稳定和代谢改变是大多数癌症的关键特征。最近的研究表明，代谢重编程是细胞对DNA损伤的系统性反应的一部分。因此，确定响应DNA损伤而微调代谢的分子将增进我们对肿瘤发生分子机制的理解，并对癌症治疗策略的开发具有深远意义。沉默调节蛋白已被确立为细胞内稳态和生理学的关键调节因子。在此，我们综述了新出现的数据，这些数据揭示了沉默调节蛋白在基因组维持和细胞代谢中的关键作用，并强调了这些关键调节因子缺陷在肿瘤发生中的表型后果的当前进展。虽然关于沉默调节蛋白的调节及其上下文依赖性功能仍有许多问题有待解决，但很明显，沉默调节蛋白可能为癌症治疗提供一条有前景、令人兴奋的新途径。
