2019年1月28日，Cell系列子刊《MolecularCell》在线发表了题为Pacer is a mediator of mTORC1 andGSK3-TIP60 signaling in regulation of autophagosome maturation and lipidmetabolism 的研究论文。 该文主要是由浙江大学基础医学院及浙大附属第二医院孙启明课题组完成，程侠卫博士（课题组博后）是论文的第一作者，孙启明研究员是该论文通讯作者。该课题受到科技部重大研发计划、国家自然科学基金和浙江省自然科学基金资助。作为合作者，北京生命科学研究所沈志荣研究员、李琳和陈涉研究员，浙江大学基础医学院刘伟教授和刘婷研究员以及浙江大学附属第二医院龚渭华教授为这个工作的完成提供了大力支持。 自噬是基于溶酶体的胞内降解途径，对维持细胞的稳态维持有重要作用。自噬参与生物体发育、免疫反应、代谢调节、细胞凋亡和衰老等多种过程。 mTORC1 和GSK3在早期自噬过程中发挥着关键作用，但如何调节自噬的步骤仍然知之甚少。这里阐释了mTORC1和GSK3-TIP60信号通路共调节自噬体通过自噬调节器Pacer成熟，作者的最近研究证实了这一点。小鼠肝细胞特异性Pacer敲除后导致受损自噬、糖原和脂质积累和肝纤维化。在营养丰富的条件下, mTORC1磷酸化Pacer的丝氨酸位点，从而失去活性；然而当营养不足时，Pacer的去磷酸化后，被TIP60分子乙酰化，促进了HOPS的招募以便更好发挥功能，从而使自噬溶酶体形成。这项工作不仅发现Pacer作为肝脏自噬和体内肝脏稳态的调节因子，同时也揭示了参与调控后期自噬和脂质代谢的信号通路机制。 其中质谱结果是由Aims质谱协助完成，找到结果中Pacer的磷酸化位点及其乙酰化位点： 经过3年的磨练捶打，Aims质谱服务商已经为上百科研实验室提供相关质谱服务，并且保质保量有口皆碑，质谱并不高端，就是您发文章锦上添花的工具，欢迎朋友前来咨询相关业务。 原文链接 AIMS---蛋白质谱服务商，提供快速便捷的 LC-MS/MS 蛋白定性/定量检测。
动物、植物管控生老病死有两把小锁，最小的（含一个 C 原子）叫甲基化，次小的（碳链含两个 C ）为乙酰化。生物体内一般都有娘胎里带来的金钥匙打开这两把小锁。 然而当碳链延长到含三个 C 的时候，小锁往往就长成了没有钥匙的镣铐，因为生物体内没有合适的酶将其解开，再加上这些生物镣铐造成的“共轭 = 交联 = 成环”自发生化反应除了两头上锁还来个中间反锁（ Amadori 重排）。这些个碳链含三个 C 以至更长一些的小分子锁（如含三个 C 的有：甲基乙二醛、丙二醛、丙烯醛、羟基丙酮醛）往往就成了生物体内的毒药，或者是抑制生命活力（如单胺神经递质）的劫匪！ 生物体从此积累应激灾变，甚至病变衰老。这个规律俺在科学网 N 年前就介绍过，这也是氧应激和糖应激衰老机理的核心机制（衰老生化机理的本质）。
大伯曾经问我：“我自从锻炼身体以后，感觉跟以前不同，是否锻炼可以改变我的基因？”这个问题让我迟疑了几秒钟。我勉强回答：“应该不会改变您的基因，但可以改变您的基因的状态。” 确实，人体内的绝大部分细胞的 DNA 序列是不会变的，但基因的表达水平会随着时间和环境因素的变化而变化。而调节这种变化的一个主要的途径是对包裹 DNA 的染色体的状态进行修饰，这些修饰包括 DNA 甲基化以及组蛋白的磷酸化、甲基化、乙酰化、泛素化等等。 一个人运动了以后，身体内的细胞肯定会接受到不同的刺激，这些刺激可以诱导以上所说的这些修饰。这是一个复杂的动态过程。 当然，代谢和染色体的修饰也有直接的联系。这种联系与乙酰辅酶 A 有关，因为乙酰辅酶 A 与细胞的合成和能量代谢有密切关系，另外，它也是蛋白乙酰化修饰的原料。
http://www.gopubmed.org/web/gopubmed/1?WEB0n4sl5oi4rmxuI1cI2mI0 2,012 documents semantically analyzed top author statistics 1 2 3 Top Years Publications 2009 228 2008 228 2007 215 2005 163 2006 159 2004 141 2003 97 2002 95 2001 64 2010 62 2000 57 1999 38 1998 33 1993 26 1995 24 1989 22 1996 21 1986 21 1990 20 1985 20 1 2 3 1 2 3 Top Countries Publications USA 895 United Kingdom 139 Japan 120 Germany 82 France 65 Italy 62 Canada 58 China 46 South Korea 29 Spain 29 India 24 Austria 21 Switzerland 20 Netherlands 18 Sweden 17 Australia 17 Taiwan 16 Belgium 13 Israel 13 Norway 12 1 2 3 1 2 3 ... 19 Top Cities Publications New York 63 Philadelphia 49 Boston 47 Bethesda 38 Houston 36 Cambridge 33 London 32 Los Angeles 31 Baltimore 29 Birmingham 23 San Francisco 21 Madison 21 Kyoto 20 Cambridge, USA 20 Tokyo 19 Rome 18 Columbus 18 Seoul 17 Montreal 17 Atlanta 16 1 2 3 ... 19 1 2 3 ... 23 Top Journals Publications J Biol Chem 240 Mol Cell Biol 121 Biochemistry-us 68 Mol Cell 59 P Natl Acad Sci Usa 55 Biochim Biophys Acta 44 Nature 30 Cancer Res 30 J Mol Biol 28 Embo J 28 Biochem J 28 Oncogene 27 Nucleic Acids Res 27 Cell 27 Science 27 Biochem Bioph Res Co 25 Eur J Biochem 22 Cell Cycle 21 Febs Lett 18 Anal Biochem 18 1 2 3 ... 23 1 2 3 ... 449 Top Terms Publications Acetylation 1,979 Lysine 1,855 cytolysis 1,547 Histones 1,318 Proteins 1,045 Animals 949 Humans 901 Genes 834 histone acetylation 801 Chromatin 743 chromatin 684 DNA 534 Methylation 527 histone h3 505 Acetyltransferases 492 methylation 467 Histone Deacetylases 444 Histone Acetyltransferases 437 Amino Acid Sequence 435 Protein Processing, Post-Translational 390 1 2 3 ... 449 1 2 3 ... 413 Top Authors Publications Allis C 36 Turner B 31 Grunstein M 17 Marmorstein R 13 Pestell R 13 Berger S 12 Erdjument-Bromage H 11 Tempst P 11 Parthun M 11 Perham R 11 Bosshard H 11 O'Neill L 10 Straehl B 10 Belyaev N 10 Allfrey V 10 Seto E 9 Cole P 9 Zhou M 9 Workman J 9 Kouzarides T 9 最新研究报道 http://news.sciencenet.cn/htmlnews/2010/2/228483.shtm 《科学》聚焦中国生物医学新成果 研究在一个全新的层面上呈现出广阔前景 美国当地时间2月19日，最新出版的《科学》杂志，罕见地同时发表两篇复旦大学生物医学研究院的最新成果。其中关于蛋白质向能量转化过程中乙酰化修饰的重要发现，对肝病、肿瘤等代谢疾病的药物研发提供了开拓性的思路，生物医学研究在一个全新的层面上呈现出广阔的前景。 2月19日，该项目的课题组负责人介绍了此项研究在药物研发等方面的意义。两篇分别题为《代谢酶的乙酰化协调碳源的利用和代谢流》和《蛋白赖氨酸的乙酰化调控》的文章，分别研究了乙酰化对蛋白质进行修饰以及对代谢通路进行调控的问题。 据介绍，人体好比一个战场，细胞就是士兵，维持着人体的基本功能；赤手空拳的蛋白质被乙酰武装起来后，才可以变成为人体作战的士兵。嫁接上一个乙酰基分子，修饰后的蛋白质就可以对细胞内的各类通路进行精确调节与控制。 乙酰调控蛋白质活性变化，使其中活跃、不活跃的部分相互平衡。而当平衡出现问题，就会导致代谢疾病。据了解，人类疾病中与代谢相关的占80%，包括肝病、肿瘤等。如果研制出一种药物能使乙酰改邪归正，对细胞进行正确调控，将成为一种全新的治疗方案。 教科书中关于代谢调控内容将有可能被改写，乙酰化修饰的概念将可能成为代谢调控新内容，相关负责人赵世民介绍说，细胞蛋白、代谢酶等大量非细胞核蛋白的乙酰化修饰，都是在研究中首次得到确认。 《科学》杂志以如此大的篇幅聚焦一个科研成果，实为罕见，充分显示了该研究的开拓性意义。《科学》的评论文章称：了解赖氨酸乙酰化是如何调控，以及改变蛋白质乙酰化对特定细胞通路的影响，对人类疾病的意义不言而喻。 更多阅读 《科学》杂志发表《蛋白赖氨酸的乙酰化调控》论文摘要（英文） 《科学》杂志发表《代谢酶的乙酰化协调碳源的利用和代谢流》论文摘要（英文） http://www.sciencemag.org/cgi/content/abstract/327/5968/1000 Science 19 February 2010: Vol. 327. no. 5968, pp. 1000 - 1004 DOI: 10.1126/science.1179689 Prev | Table of Contents | Next Reports Regulation of Cellular Metabolism by Protein Lysine Acetylation Shimin Zhao, 1 ,2 Wei Xu, 1 ,2 ,* Wenqing Jiang, 1 ,2 ,* Wei Yu, 1 ,2 Yan Lin, 2 Tengfei Zhang, 1 ,2 Jun Yao, 3 Li Zhou, 4 Yaxue Zeng, 4 Hong Li, 5 Yixue Li, 6 Jiong Shi, 6 Wenlin An, 7 Susan M. Hancock, 7 Fuchu He, 3 Lunxiu Qin, 5 Jason Chin, 7 Pengyuan Yang, 3 Xian Chen, 3 ,4 Qunying Lei, 1 ,2 ,8 Yue Xiong, 1 ,2 ,4 , Kun-Liang Guan 1 ,2 ,8 ,9 , Protein lysine acetylation has emerged as a key posttranslational modification in cellular regulation, in particular through the modification of histones and nuclear transcription regulators. We show that lysine acetylation is a prevalent modification in enzymes that catalyze intermediate metabolism. Virtually every enzyme in glycolysis, gluconeogenesis, the tricarboxylic acid (TCA) cycle, the urea cycle, fatty acid metabolism, and glycogen metabolism was found to be acetylated in human liver tissue. The concentration of metabolic fuels, such as glucose, amino acids, and fatty acids, influenced the acetylation status of metabolic enzymes. Acetylation activated enoylcoenzyme A hydratase/3-hydroxyacylcoenzyme A dehydrogenase in fatty acid oxidation and malate dehydrogenase in the TCA cycle, inhibited argininosuccinate lyase in the urea cycle, and destabilized phosphoenolpyruvate carboxykinase in gluconeogenesis. Our study reveals that acetylation plays a major role in metabolic regulation. 1 School of Life Sciences, Fudan University, Shanghai 20032, China. 2 Molecular and Cell Biology Lab, Fudan University, Shanghai 20032, China. 3 Center of Proteomics, Institute of Biomedical Sciences, Fudan University, Shanghai 20032, China. 4 Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA. 5 Affiliated Zhongshan Hospital, Fudan University, Shanghai 20032, China. 6 Bioinformatics Center, Key Lab of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. 7 Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 OQH, UK. 8 Department of Biological Chemistry, Fudan University, Shanghai 20032, China. 9 Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA. Science 19 February 2010: Vol. 327. no. 5968, pp. 1004 - 1007 DOI: 10.1126/science.1179687 Prev | Table of Contents | Next Reports Acetylation of Metabolic Enzymes Coordinates Carbon Source Utilization and Metabolic Flux Qijun Wang, 1 Yakun Zhang, 2 Chen Yang, 3 Hui Xiong, 1 ,2 Yan Lin, 4 Jun Yao, 4 Hong Li, 3 Lu Xie, 3 Wei Zhao, 3 Yufeng Yao, 5 Zhi-Bin Ning, 3 Rong Zeng, 3 Yue Xiong, 4 ,6 Kun-Liang Guan, 4 ,7 Shimin Zhao, 1 ,4 ,* Guo-Ping Zhao 1 ,2 ,3 ,8 ,* Lysine acetylation regulates many eukaryotic cellular processes, but its function in prokaryotes is largely unknown. We demonstrated that central metabolism enzymes in Salmonella were acetylated extensively and differentially in response to different carbon sources, concomitantly with changes in cell growth and metabolic flux. The relative activities of key enzymes controlling the direction of glycolysis versus gluconeogenesis and the branching between citrate cycle and glyoxylate bypass were all regulated by acetylation. This modulation is mainly controlled by a pair of lysine acetyltransferase and deacetylase, whose expressions are coordinated with growth status. Reversible acetylation of metabolic enzymes ensure that cells respond environmental changes via promptly sensing cellular energy status and flexibly altering reaction rates or directions. It represents a metabolic regulatory mechanism conserved from bacteria to mammals. 1 State Key Laboratory of Genetic Engineering, Department of Microbiology, School of Life Sciences and Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China. 2 MOST-Shanghai Laboratory of Disease and Health Genomics, Chinese National Human Genome Center at Shanghai, Shanghai 201203, China. 3 Key Laboratory of Synthetic Biology, Bioinformatics Center and Laboratory of Systems Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China. 4 Molecular Cell Biology Laboratory, Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China. 5 Laboratory of Human Bacterial Pathogenesis, Department of Medical Microbiology and Parasitology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. 6 Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. 7 Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA. 8 Department of Microbiology and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China. * To whom correspondence should be addressed. E-mail: zhaosm@fudan.edu.cn
标签: 乙酰化
