Sirtuins and disease: the road ahead.
Sirtuins and disease: the road ahead.
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DOI：
10.3389/fphar.2012.00004
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发表时间：
2012
影响因子：
5.6
通讯作者：
Altucci L
中科院分区：
文献类型：
--
作者：
Carafa V;Nebbioso A;Altucci L
Sirtuins代表了一类有前途的新的保守组蛋白脱乙酰酶，最初在酵母中鉴定。Sirtuin（SirT）家族的活性-由七个成员（SirT 1 -7）组成-是NAD+依赖性的。Sirtuins靶向细胞核、细胞质和线粒体中的多种细胞蛋白，通过乙酰化（SirT 1、2、3和5）或ADP-核糖基化（SirT 4和6）进行翻译后修饰。Sirtuins调节对压力的反应，并确保受损的DNA不会繁殖，从而与突变的积累形成对比。迄今为止，沉默调节蛋白已成为治疗人类病理学如代谢、心血管和神经退行性疾病以及癌症的潜在治疗靶标。SirT 1是这类酶的创始成员，目前是该组中最知名的。SirT 1在各种细胞过程中起作用，使染色质和非组蛋白蛋白脱乙酰化，其在癌症和衰老中的作用已被广泛研究。SirT 1可能通过阻断衰老和凋亡、促进细胞生长和血管生成，在肿瘤的发生和发展以及耐药性中发挥关键作用。最近，对沉默调节蛋白的兴趣日益增长，导致了能够改变沉默调节蛋白活性的小分子的发现和表征。本综述强调了SirT在癌症中的作用和失调机制，重点介绍了SirT调节剂在癌症预防和治疗中的治疗潜力。
Sirtuins represent a promising new class of conserved histone deacetylases, originally identified in yeast. The activity of the sirtuin (SirT) family – made up of seven members (SirT1-7) – is NAD+ dependent. Sirtuins target a wide range of cellular proteins in nucleus, cytoplasm, and mitochondria for post-translational modification by acetylation (SirT1, 2, 3, and 5) or ADP-ribosylation (SirT4 and 6). Sirtuins regulate responses to stress and ensure that damaged DNA is not propagated, thus contrasting the accumulation of mutations. To date, sirtuins have emerged as potential therapeutic targets for treatment of human pathologies such as metabolic, cardiovascular and neurodegenerative diseases, and cancer. SirT1 is the founding member of this class of enzymes and is currently the best known of the group. SirT1 acts in various cellular processes, deacetylating both chromatin and non-histone proteins, and its role in cancer and aging has been extensively studied. SirT1 may play a critical role in tumor initiation and progression as well as drug resistance by blocking senescence and apoptosis, and by promoting cell growth and angiogenesis. Recently, growing interest in sirtuin modulation has led to the discovery and characterization of small molecules able to modify sirtuin activity. The present review highlights SirT mechanism(s) of action and deregulation in cancer, focusing on the therapeutic potential of SirT modulators both in cancer prevention and treatment.
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影响因子：
3.7
作者：
Ouaissi, Mehdi;Sielezneff, Igor;Ouaissi, Ali
通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
Shogren-Knaak, M;Ishii, H;Peterson, CL
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DOI：
10.1073/pnas.261574398
发表时间：
2001-12-18
影响因子：
11.1
作者：
Bedalov, A;Gatbonton, T;Simon, JA
通讯作者：
Simon, JA
影响因子：
5.7
作者：
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通讯作者：
Plotnikov, Alexander N.