Zschoernig Barbara, Mahlknecht Ulrich
Saarland University Medical Center, Department of Internal Medicine, Division of Immunotherapy and Gene Therapy, José Carreras Center for Immunotherapy and Gene Therapy, Kirrberger Strasse, Building 40, D-66421 Homburg/Saar, Germany.
Biochem Biophys Res Commun. 2008 Nov 14;376(2):251-5. doi: 10.1016/j.bbrc.2008.08.137. Epub 2008 Sep 5.
Earlier analyses on the sirtuin family of histone deacetylases and its well-known member SIRT1 had their primary focus mostly on the identification of cellular targets exploring molecular mechanisms and functional networks in the control of metabolic homeostasis, differentiation, apoptosis and cell survival. However, only little is known about the regulation of SIRT1 itself, so far. Presently, SIRT1 is gaining increasing importance in the development of innovative treatment strategies for cancer, neurodegenerative disorders and metabolic disease. Based on differences in their catalytic activities, SIRT1 and the sirtuins in general, are insensitive to the classical class I and II HDAC inhibitors which are increasingly becoming part of treatment regimens for solid tumors and hematological malignancies. In this review we outline recent research advances on the regulation of SIRT1 which may provide the basis for the development of therapeutic inhibitors with improved specificity.
早期对组蛋白去乙酰化酶的沉默调节蛋白家族及其著名成员SIRT1的分析主要集中在确定细胞靶点，探索控制代谢稳态、分化、凋亡和细胞存活的分子机制和功能网络。然而，到目前为止，关于SIRT1自身的调节知之甚少。目前，SIRT1在癌症、神经退行性疾病和代谢疾病创新治疗策略的开发中越来越重要。基于其催化活性的差异，SIRT1以及一般的沉默调节蛋白对经典的I类和II类HDAC抑制剂不敏感，而这些抑制剂正日益成为实体瘤和血液系统恶性肿瘤治疗方案的一部分。在本综述中，我们概述了SIRT1调节方面的最新研究进展，这可能为开发具有更高特异性的治疗抑制剂提供基础。
