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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A phylogenetically conserved NAD~+-dependent protein deacetylase activity in the Sir2 protein family
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A phylogenetically conserved NAD~+-dependent protein deacetylase activity in the Sir2 protein family

机译：Sir2蛋白家族中系统发育的NAD〜+依赖性蛋白脱乙酰酶活性

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摘要

The yeast Sir2 protein. required for transcriptional silencing. has an NAD~+-dependent histone deacetylase (HDA) activity. Yeast extracts contain a NAD~+-dependent HDA activity that is elimi- nated in a yeast strain from which SIR2 and its, four homologs have been deleted. This HDA activity is also displayed by purified yeast Sir2p and homologous Archaeal, eubacterial, and human proteins, and depends completely on NAD~+ in all species tested. The yeast NPT1 gene, encoding an important NAD~+ synthesis enzyme, is required for rDNA and telomeric silencing and con- tributes to silencing of the HM loci. Null mutants in this gene have significantly reduced intracellular NAD~+ concentrations and have phenotypes similar to sir2 null mutants. Surprisingly, yeast from which all five SIR2 homologs have been deleted have relatively normal bulk histone acetylation levels. The evolution- ary conservation of this regulated activity suggests that the Sir2 protein family represents a set of effector proteins in an evo- lutionarily conserved signal transduction pathway that monitors cellular energy and redox states.
机译：酵母Sir2蛋白。转录沉默所需。具有NAD〜+依赖的组蛋白脱乙酰基酶（HDA）活性。酵母提取物中含有NAD〜+依赖性的HDA活性，在酵母菌株中已被消除，SIR2及其四个同源物已被删除。纯化的酵母Sir2p以及同源的古细菌，真细菌和人类蛋白质也显示出这种HDA活性，并且在所有测试物种中完全依赖于NAD〜+。酵母NPT1基因编码重要的NAD〜+合成酶，是rDNA和端粒沉默所需的，并有助于HM基因座的沉默。该基因中的无效突变体具有明显降低的细胞内NAD +浓度，并且具有与sir2无效突变体相似的表型。令人惊讶地，从中删除了所有五个SIR2同源物的酵母具有相对正常的整体组蛋白乙酰化水平。这种调节活性的进化保守性表明，Sir2蛋白家族在监测细胞能量和氧化还原状态的进化保守信号转导途径中代表了一组效应蛋白。

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