Laboratoire d'Immunobiologie, Institut de Biologie et Médecine Moléculaires, Université Libre de Bruxelles, Gosselies, Belgium.
Biochem Pharmacol. 2011 Mar 1;81(5):569-76. doi: 10.1016/j.bcp.2010.12.010. Epub 2010 Dec 22.
Lysine acetylation/deacetylation has been recognized as an important posttranslational modification regulating numerous cellular processes. Sirtuins represent novel players in these complex regulatory circuits. These NAD-dependent lysine-deacetylases have attracted much interest based on their role in the regulation of lifespan in lower organisms, and their capacity to interfere with cell growth, proliferation and survival in response to stress. Their absolute requirement for NAD suggests that these enzymes may represent an important molecular link between metabolism and several human disorders such as diabetes and cancer. More recently, the identification of several transcription factors known to play a role in the immune system as sirtuin substrates has suggested that this family of enzymes may also play an important role in the regulation of inflammation, a pathological situation with clear links to metabolism and aging in humans. We review herein the possible links between nuclear sirtuins and the regulation of an immune response, and discuss the possible strategies that may lead to the development of novel therapeutic approaches to treat inflammation by targeting sirtuin activity.
赖氨酸乙酰化/去乙酰化已被认为是调节许多细胞过程的一种重要的翻译后修饰。Sirtuins 是这些复杂调节回路中的新型参与者。这些依赖 NAD 的赖氨酸去乙酰化酶因其在低等生物寿命调节中的作用以及在应激反应中干扰细胞生长、增殖和存活的能力而引起了广泛关注。它们对 NAD 的绝对需求表明，这些酶可能是代谢与糖尿病和癌症等几种人类疾病之间的重要分子联系。最近，鉴定出几种已知在免疫系统中作为 Sirtuins 底物发挥作用的转录因子表明，该酶家族也可能在炎症的调节中发挥重要作用，炎症是一种与人类代谢和衰老有明确联系的病理情况。本文综述了核 Sirtuins 与免疫反应调节之间的可能联系，并讨论了可能的策略，这些策略可能通过靶向 Sirtuins 活性来开发治疗炎症的新的治疗方法。
