Mol Cell:SIRT5介导的蛋白琥珀酰修饰通路研究获突破

2013-12-21 黄辛 中国科学报

近日,中科院上海药物所化学蛋白质组学研究中心与美国芝加哥大学、密歇根大学在一项合作研 究中,首次在哺乳动物细胞中对去乙酰化调控酶Sirt5调控的琥珀酰底物进行了系统的蛋白质组学研究,在779个蛋白上鉴定出2500多个琥珀酰位点,并研究揭示了蛋白琥珀酰修饰具有广泛调节细胞代谢的作用,同时也提示此修饰可能影响其他重要细胞生物学功能。相关研究成果日前发表于最新一期的《分子细胞》 杂志。 &nbsp

近日,中科院上海药物所化学蛋白质组学研究中心与美国芝加哥大学、密歇根大学在一项合作研 究中,首次在哺乳动物细胞中对去乙酰化调控酶Sirt5调控的琥珀酰底物进行了系统的蛋白质组学研究,在779个蛋白上鉴定出2500多个琥珀酰位点,并研究揭示了蛋白琥珀酰修饰具有广泛调节细胞代谢的作用,同时也提示此修饰可能影响其他重要细胞生物学功能。相关研究成果日前发表于最新一期的《分子细胞》 杂志。
 
据介绍,蛋白翻译后修饰对蛋白质的结构和功能起着关键作用,是细胞精细调节生理活动的关键之一。因而,蛋白翻译后修饰通路研究是目前新药研发的重要热点之一。
 
    研究人员通过综合运用生物质谱、生物化学和生物信息学方法,证明琥珀酰化广泛存在于线粒体能量代谢调控酶中,参与调控包括三羧酸循环、氨基酸代谢以及脂肪酸代谢在内的多个代谢信号通路。同时,研究人员也发现琥珀酰化存在于细胞浆和细胞核蛋白中,并揭示了琥珀酰化能抑制丙酮酸脱氢酶和琥珀酸脱氢酶复合物活性。

原始出处:

Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y.SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways. Mol Cell. 2013 Jun 27;50(6):919-30.

相关文献:

Rardin MJ, He W, Nishida Y, Newman JC, Carrico C, Danielson SR, Guo A, Gut P, Sahu AK, Li B, Uppala R, Fitch M, Riiff T, Zhu L, Zhou J, Mulhern D, Stevens RD, Ilkayeva OR, Newgard CB, Jacobson MP, Hellerstein M, Goetzman ES, Gibson BW, Verdin E.SIRT5 Regulates the Mitochondrial Lysine Succinylome and Metabolic Networks.Cell Metab. 2013 Dec 3;18(6):920-33.


Liu B, Che W, Zheng C, Liu W, Wen J, Fu H, Tang K, Zhang J, Xu Y.SIRT5: a safeguard against oxidative stress-induced apoptosis in cardiomyocytes.Cell Physiol Biochem. 2013;32(4):1050-9.

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    2014-02-07 维他命
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