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1.发明申请METHODS FOR IDENTIFYING AGENTS WHICH ALTER HISTONE PROTEIN ACETYLATION, DECREASE AGING OR INCREASE LIFESPAN 有权用于鉴定肝细胞蛋白质乙酰化，降解衰老或增加生殖激素的药剂的方法公开(公告)号：US20090155834A1
公开(公告)日：2009-06-18
申请号：US12209847
申请日：2008-09-12
CPC分类号： G01N33/66 , A61K38/1709 , C12Q1/48 , G01N2500/00 , Y02A50/473 , A61K2300/00
摘要： Methods of identifying agents which alter the NAD-dependent acetylation status and mono-ADP-ribosylation of nuclear proteins are disclosed. The methods further include identifying agents which alter the life span or aging of a cell or an organism by determining the level of NAD-dependent acetylation and/or ADP ribosylation of a nuclear protein. The invention also relates to a mammalian Sir2 protein which acetylates or deacetylates nuclear proteins in a NAD-dependent manner and has mono-ADP-ribosyltransferase activity. Host cells producing the Sir2 protein and antibodies to the Sir2 protein are also provided.
摘要翻译： 公开了鉴定改变核蛋白的NAD依赖性乙酰化状态和单ADP-核糖基化的试剂的方法。 所述方法还包括通过确定核蛋白的NAD依赖性乙酰化和/或ADP核糖基化的水平来鉴定改变细胞或生物体的寿命或衰老的试剂。 本发明还涉及哺乳动物Sir2蛋白，其以NAD依赖性方式乙酰化或脱乙酰化核蛋白并具有单ADP-核糖基转移酶活性。 还提供了产生Sir2蛋白的宿主细胞和Sir2蛋白的抗体。
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公开(公告)号：US20070099830A1
公开(公告)日：2007-05-03
申请号：US11409170
申请日：2006-04-21
申请人： Leonard Guarente , Marcia Haigis
发明人： Leonard Guarente , Marcia Haigis
CPC分类号： C12N15/1137 , C12N9/80 , C12Q1/48 , G01N2333/91142
摘要： It has been discovered that Sirt4 possesses an ADP-ribosyltransferase activity. Sirt4 is localized to mitochondria, where it binds to and regulates the activity of proteins such as glutamate dehydrogenase. The ADP-ribosyltransferase activity of Sirt4 is important for the regulation of biological functions such as insulin secretion. Methods of screening for compounds that modulate the expression or activity of Sirt4 are provided. Also provided are methods of modulating insulin secretion, treating metabolic disorders, and treating neurodegenerative disorders by modulating the expression or activity of Sirt4.
摘要翻译： 已经发现Sirt4具有ADP-核糖基转移酶活性。 Sirt4被定位于线粒体，其中它结合并调节蛋白质如谷氨酸脱氢酶的活性。 Sirt4的ADP-核糖基转移酶活性对调节生物学功能如胰岛素分泌是重要的。 提供筛选调节Sirt4表达或活性的化合物的方法。 还提供了调节胰岛素分泌，治疗代谢紊乱和通过调节Sirt4的表达或活性来治疗神经变性疾病的方法。
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公开(公告)号：US20100105036A1
公开(公告)日：2010-04-29
申请号：US12408575
申请日：2009-03-20
CPC分类号： C12Q1/68 , C12Q1/44 , G01N2333/4703 , G01N2333/916 , G01N2500/02
摘要： This invention relates to methods of screening compounds that modulate cellular and organismal processes by modification of the activity of SIR2 and/or transcription factors, e.g., p53, particularly methods of screening for compounds that modify lifespan and/or metabolism of a cell or an organism by modulation of the activity of SIR2 and/or transcription factors, e.g., p53, and more particularly to methods of screening for compounds that modulate the activity of Sir2 and/or transcription factors, e.g., p53. In particular, the present invention relates to a method for screening a compound, by providing a test mixture comprising a transcription factor, Sir2, and a Sir2 cofactor with the compound, and evaluating an activity of a component of the test mixture in the presence of the compound. The invention further relates to therapeutic uses of said compounds. The invention further relates to a method of modifying the acetylation status of a transcription factor binding site on histone or DNA by raising local concentrations of Sir2.
摘要翻译： 本发明涉及通过修饰SIR2和/或转录因子活性（例如p53）来筛选调节细胞和生物体过程的化合物的方法，特别是筛选修饰细胞或生物体的寿命和/或代谢的化合物的方法 通过调节SIR2和/或转录因子例如p53的活性，更具体地涉及筛选调节Sir2和/或转录因子例如p53的活性的化合物的方法。 特别地，本发明涉及通过提供包含转录因子Sir2和Sir2辅因子与该化合物的测试混合物来筛选化合物的方法，并且在存在下评价测试混合物的组分的活性 化合物。 本发明还涉及所述化合物的治疗用途。 本发明还涉及通过提高Sir2的局部浓度来改变组蛋白或DNA上的转录因子结合位点的乙酰化状态的方法。
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公开(公告)号：US20060252076A1
公开(公告)日：2006-11-09
申请号：US11404146
申请日：2006-04-13
CPC分类号： C12Q1/68 , C12Q1/44 , G01N2333/4703 , G01N2333/916 , G01N2500/02
摘要： This invention relates to methods of screening compounds that modulate cellular and organismal processes by modification of the activity of SIR2 and/or transcription factors, e.g., p53, particularly methods of screening for compounds that modify lifespan and/or metabolism of a cell or an organism by modulation of the activity of SIR2 and/or transcription factors, e.g., p53, and more particularly to methods of screening for compounds that modulate the activity of Sir2 and/or transcription factors, e.g., p53. In particular, the present invention relates to a method for screening a compound, by providing a test mixture comprising a transcription factor, Sir2, and a Sir2 cofactor with the compound, and evaluating an activity of a component of the test mixture in the presence of the compound. The invention further relates to therapeutic uses of said compounds. The invention further relates to a method of modifying the acetylation status of a transcription factor binding site on histone or DNA by raising local concentrations of Sir2.
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5.发明授权公开(公告)号：US08652797B2
公开(公告)日：2014-02-18
申请号：US12209847
申请日：2008-09-12
CPC分类号： G01N33/66 , A61K38/1709 , C12Q1/48 , G01N2500/00 , Y02A50/473 , A61K2300/00
摘要： Methods of NAD-dependent of at least one lysine residue in an acetylated protein are disclosed. The methods include combining the acetylated protein with an isolated Sir2 protein or fragment that includes a core domain of the Sir2 protein. The Sir2 protein or fragment of the Sir2 protein can include a human Sir2 protein or a fragment of a human Sir2 protein.
摘要翻译： 公开了乙酰化蛋白中至少一个赖氨酸残基的NAD依赖性的方法。 所述方法包括将乙酰化蛋白与包含Sir2蛋白的核心结构域的分离的Sir2蛋白或片段组合。 Sir2蛋白或Sir2蛋白的片段可以包括人Sir2蛋白或人Sir2蛋白的片段。
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公开(公告)号：US20130071378A1
公开(公告)日：2013-03-21
申请号：US13523412
申请日：2012-06-14
IPC分类号： C12Q1/68
CPC分类号： C12Q1/68 , C12Q1/44 , G01N2333/4703 , G01N2333/916 , G01N2500/02
摘要： Methods for screening a compound, by providing a test mixture comprising a transcription factor, Sir2, and a Sir2 cofactor with the compound, and evaluating an activity of a component of the test mixture in the presence of the compound are described.
摘要翻译： 描述了通过向化合物提供包含转录因子Sir2和Sir2辅因子的测试混合物并在化合物存在下评价测试混合物的组分的活性来筛选化合物的方法。
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7.发明申请SIRTUIN BASED METHODS AND COMPOSITIONS FOR TREATING BETA-CATENIN-RELATED CONDITIONS 审中-公开基于SIRTUIN的方法和组合物用于治疗与β-卡培宁相关的病症公开(公告)号：US20110009474A1
公开(公告)日：2011-01-13
申请号：US12595353
申请日：2008-04-14
IPC分类号： A61K31/7088 , A61P35/00 , A61P17/02 , A61P13/12 , A61P19/04 , A61P17/00 , A61P37/00 , C12N5/02 , G01N33/566
CPC分类号： A61K38/50
摘要： Provided herein are methods and compositions relating to sirtuin modulation of Wnt pathway signaling, including the use of sirtuin and sirtuin-modulating agents in the prevention and treatment of cancer and other diseases.
摘要翻译： 本文提供了关于Wnt途径信号传递的沉默调节调节的方法和组合物，包括在预防和治疗癌症和其它疾病中使用沉默调节蛋白和沉默调节蛋白的调节剂。
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公开(公告)号：US07572575B2
公开(公告)日：2009-08-11
申请号：US11404146
申请日：2006-04-13
IPC分类号： C12Q1/00 , G01N33/53 , G01N33/567
CPC分类号： C12Q1/68 , C12Q1/44 , G01N2333/4703 , G01N2333/916 , G01N2500/02
摘要： This invention relates to methods of screening compounds that modulate cellular and organismal processes by modification of the activity of SIR2 and/or transcription factors, e.g., p53, particularly methods of screening for compounds that modify lifespan and/or metabolism of a cell or an organism by modulation of the activity of SIR2 and/or transcription factors, e.g., p53, and more particularly to methods of screening for compounds that modulate the activity of Sir2 and/or transcription factors, e.g., p53. In particular, the present invention relates to a method for screening a compound, by providing a test mixture comprising a transcription factor, Sir2, and a Sir2 cofactor with the compound, and evaluating an activity of a component of the test mixture in the presence of the compound. The invention further relates to therapeutic uses of said compounds. The invention further relates to a method of modifying the acetylation status of a transcription factor binding site on histone or DNA by raising local concentrations of Sir2.
摘要翻译： 本发明涉及通过修饰SIR2和/或转录因子（例如p53）的活性来调节细胞和生物体过程的化合物的方法，特别是筛选修饰细胞或生物体的寿命和/或代谢的化合物的方法 通过调节SIR2和/或转录因子例如p53的活性，更具体地涉及筛选调节Sir2和/或转录因子例如p53的活性的化合物的方法。 特别地，本发明涉及通过提供包含转录因子Sir2和Sir2辅因子与该化合物的测试混合物来筛选化合物的方法，并且在存在下评价测试混合物的组分的活性 化合物。 本发明还涉及所述化合物的治疗用途。 本发明还涉及通过提高Sir2的局部浓度来改变组蛋白或DNA上的转录因子结合位点的乙酰化状态的方法。
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公开(公告)号：US20050009169A1
公开(公告)日：2005-01-13
申请号：US10912434
申请日：2004-08-05
IPC分类号： C07K14/395 , C12Q1/02 , C12Q1/00 , C12N1/20
CPC分类号： C12Q1/025 , C07K14/395 , C12R1/865
摘要： Methods of isolating mutant yeast cells with increased life span, as well as mutant yeast cells isolated by the methods, are disclosed. Also described are methods of identifying agents which increase life span of yeast cells, and methods of isolating genes which affect senescence in organisms.
摘要翻译： 公开了分离增加寿命的突变酵母细胞的方法，以及通过该方法分离的突变酵母细胞。 还描述了鉴定增加酵母细胞寿命的试剂的方法，以及分离影响生物衰老的基因的方法。
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10.发明授权公开(公告)号：US07452664B2
公开(公告)日：2008-11-18
申请号：US09461580
申请日：1999-12-15
CPC分类号： G01N33/66 , A61K38/1709 , C12Q1/48 , G01N2500/00 , Y02A50/473 , A61K2300/00
摘要： Methods of identifying agents which alter the NAD-dependent acetylation status and mono-ADP-ribosylation of nuclear proteins are disclosed. The methods further include identifying agents which alter the life span or aging of a cell or an organism by determining the level of NAD-dependent acetylation and/or ADP ribosylation of a nuclear protein. The invention also relates to a mammalian Sir2 protein which acetylates or deacetylates nuclear proteins in a NAD-dependent manner and has mono-ADP-ribosyltransferase activity. Host cells producing the Sir2 protein and antibodies to the Sir2 protein are also provided.
摘要翻译： 公开了鉴定改变核蛋白的NAD依赖性乙酰化状态和单ADP-核糖基化的试剂的方法。 所述方法还包括通过确定核蛋白的NAD依赖性乙酰化和/或ADP核糖基化的水平来鉴定改变细胞或生物体的寿命或衰老的试剂。 本发明还涉及哺乳动物Sir2蛋白，其以NAD依赖性方式乙酰化或脱乙酰化核蛋白并具有单ADP-核糖基转移酶活性。 还提供了产生Sir2蛋白的宿主细胞和Sir2蛋白的抗体。
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