SIRT5, functions in cellular metabolism with a multiple enzymatic activities
SIRT5, functions in cellular metabolism with a multiple enzymatic activities
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DOI：
10.1007/s11427-015-4902-8
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发表时间：
2015-07
期刊：
影响因子：
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通讯作者：
Xin Yang;Boya Liu;Wei-Guo Zhu;Jianyuan Luo
中科院分区：
文献类型：
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作者：
Xin Yang;Boya Liu;Wei-Guo Zhu;Jianyuan Luo
哺乳动物Sirtuins是酵母Saccharomyces cerevisiae Sir 2（沉默信息调节因子2）的同源物，其在染色质沉默中起作用，以通过催化组蛋白脱乙酰化来防止基因组不稳定性和老化[1]。Sirtuin家族有7个成员（SIRT 1-SIRT 7）。它们都含有进化上保守的酶结构域，即依赖于烟酰胺腺嘌呤二核苷酸（NAD）的组蛋白脱乙酰基酶，该酶靶向多种组蛋白或非组蛋白发挥生物学功能。每种Sirtuins都具有独特的功能和细胞定位。SIRT 1、6和7定位于细胞核，SIRT 2定位于细胞质，而SIRT 3、4和5定位于线粒体[2]。SIRT 5是Sirtuin家族中的独特成员，因为它含有多种酶活性。它最初被报道为NAD依赖性组蛋白脱乙酰酶[3]，最近发现SIRT 5还含有NAD依赖性蛋白赖氨酸脱丙二酸酶和脱琥珀酰酶活性[4];以及赖氨酸戊二酸酶活性[5]。SIRT 5的多种酶活性表明SIRT 5是一种在细胞代谢调控中具有多种功能的蛋白质。在这里，我们将讨论SIRT 5的多种酶活性如何调节细胞代谢。
Mammalian Sirtuins are the homologs of yeast Saccharomyces cerevisiae Sir2 (silent information regulator 2), which functions in chromatin silencing to prevent genomic instability and aging by catalyzing the histone deacetylation [1]. There are seven members in Sirtuin family (SIRT1-SIRT7). They all contain evolutionary conserved enzymatic domain which is nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase that targets a wide variety of histone or non-histone proteins for biological functions. Each of the Sirtuins has distinctive functions and cellular localization. SIRT1, 6 & 7 are localized in nucleus, and SIRT2 is localized at cytoplasm while SIRT3, 4 & 5 are localized in mitochondria [2]. SIRT5 is a unique member among the Sirtuin family because it contains multiple enzymatic activities. It was initially reported as a NAD-dependent histone deacetylase [3], More recently, SIRT5 has been found that it also contains a NAD-dependent protein lysine demalonylase and desuccinylase activities [4]; and lysine glutarylase activity [5]. The multiple enzymatic activities of SIRT5 indicate that SIRT5 is a multiple functional proteins in its regulation of cellular metabolism. Here, we will discuss how multiple enzymatic activities of SIRT5 in regulation of cellular metabolism.