Fiorentino Francesco, Carafa Vincenzo, Favale Gregorio, Altucci Lucia, Mai Antonello, Rotili Dante
Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK.
Department of Precision Medicine, Università degli Studi della Campania "L. Vanvitelli", 80138 Naples, Italy.
Cancers (Basel). 2021 Mar 8;13(5):1156. doi: 10.3390/cancers13051156.
Sirtuin 6 (SIRT6) is a NAD-dependent nuclear deacylase and mono-ADP-ribosylase with a wide spectrum of substrates. Through its pleiotropic activities, SIRT6 modulates either directly or indirectly key processes linked to cell fate determination and oncogenesis such as DNA damage repair, metabolic homeostasis, and apoptosis. SIRT6 regulates the expression and activity of both pro-apoptotic (e.g., Bax) and anti-apoptotic factors (e.g., Bcl-2, survivin) in a context-depending manner. Mounting evidence points towards a double-faced involvement of SIRT6 in tumor onset and progression since the block or induction of apoptosis lead to opposite outcomes in cancer. Here, we discuss the features and roles of SIRT6 in the regulation of cell death and cancer, also focusing on recently discovered small molecule modulators that can be used as chemical probes to shed further light on SIRT6 cancer biology and proposed as potential new generation anticancer therapeutics.
沉默调节蛋白6（SIRT6）是一种依赖烟酰胺腺嘌呤二核苷酸（NAD）的核去乙酰化酶和单ADP核糖基化酶，具有广泛的底物。通过其多效性活动，SIRT6直接或间接调节与细胞命运决定和肿瘤发生相关的关键过程，如DNA损伤修复、代谢稳态和细胞凋亡。SIRT6以上下文依赖的方式调节促凋亡因子（如Bax）和抗凋亡因子（如Bcl-2、生存素）的表达和活性。越来越多的证据表明，SIRT6在肿瘤发生和进展中具有两面性作用，因为细胞凋亡的阻断或诱导在癌症中会导致相反的结果。在这里，我们讨论SIRT6在细胞死亡调节和癌症中的特征和作用，还将重点关注最近发现的小分子调节剂，这些调节剂可用作化学探针，以进一步阐明SIRT6的癌症生物学，并被提议作为潜在的新一代抗癌治疗药物。
