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261.
Lin YY Kiihl S Suhail Y Liu SY Chou YH Kuang Z Lu JY Khor CN Lin CL Bader JS Irizarry R Boeke JD 《Nature》2012,482(7384):251-255
First identified as histone-modifying proteins, lysine acetyltransferases (KATs) and deacetylases (KDACs) antagonize each other through modification of the side chains of lysine residues in histone proteins. Acetylation of many non-histone proteins involved in chromatin, metabolism or cytoskeleton regulation were further identified in eukaryotic organisms, but the corresponding enzymes and substrate-specific functions of the modifications are unclear. Moreover, mechanisms underlying functional specificity of individual KDACs remain enigmatic, and the substrate spectra of each KDAC lack comprehensive definition. Here we dissect the functional specificity of 12 critical human KDACs using a genome-wide synthetic lethality screen in cultured human cells. The genetic interaction profiles revealed enzyme-substrate relationships between individual KDACs and many important substrates governing a wide array of biological processes including metabolism, development and cell cycle progression. We further confirmed that acetylation and deacetylation of the catalytic subunit of the adenosine monophosphate-activated protein kinase (AMPK), a critical cellular energy-sensing protein kinase complex, is controlled by the opposing catalytic activities of HDAC1 and p300. Deacetylation of AMPK enhances physical interaction with the upstream kinase LKB1, leading to AMPK phosphorylation and activation, and resulting in lipid breakdown in human liver cells. These findings provide new insights into previously underappreciated metabolic regulatory roles of HDAC1 in coordinating nutrient availability and cellular responses upstream of AMPK, and demonstrate the importance of high-throughput genetic interaction profiling to elucidate functional specificity and critical substrates of individual human KDACs potentially valuable for therapeutic applications. 相似文献
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在假设ITAM两步磷酸化的基础上,建立理论模型,定性讨论了ZAP-70在ITAM活化中的作用.结果表明:TCR与MHC-pep抗原多肽的亲和力是影响免疫应答的一个重要参数,但ZAP-70对ITAM活化事件的正反馈调节会使得TCR对特异性抗原识别的敏锐性降低,当这种调节达到一定程度时,免疫应答将不再依赖抗原的特异性.进一步讨论了半活化状态的ZAP-70的作用,运用此模型还解释了ITAM的活化过程存在一个ITAM/ZAP-70的浓度阈值问题. 相似文献
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The complex [closo-3,3-(PPh_3)_2-3-H-3,1,2-RhC_2B_9H_(11)]has a rich derivative chemistrythat is currently under active investigation.The resultant compound shows an increasing stabilitythat is often associated with metallocarboranes.This paper deals with the novel and the produc-tion area of carborane complexes of transition metals.The paper indicates that some reactions can easily proceed and the resulting compound hassome new properties and uses.K[18-crown-6][closo-3-Ph_3P-3-CH_2Ph-3-Br-3,1,2-RhC_2B_9H_(11)]can be synthesized by the reaction of K[18-crown-6][(Ph_3P)_2RhC_2B_9H_(11)]withbromo-toluene under the condition of dry benzene.IR and ~1H,~(11)B,~(31)p nuclear magnetic reso-nance and elemental analysis comfirm the structure for this species with one carborane groupbonded to the central metal. 相似文献
266.
By analyzing U and Th isotopic compositions of 41 samples in two stalagmites from Hulu Cave, Nanjing, we first discovered that variations of 238U and d 234U0 along the stalagmite growth-sequence (covering a period from 75 to 18 kaBP) are in high similarity to summer insolation curve at 33°N and d 18O-based climate record of the studied stalagmites. The concentration of 238U is mainly controlled by content of organic matter in the soil above the cave. This mechanism can be used to explain our result that 238U curve of stalagmites is in phase with fluctuation of the d 18O record of the same stalagmites and summer insolation at cave locality. However, 238U concentration curve vs. age is, in amplitude, inconsistent with the climatic curves, possibly due to complex processes of soil-water-rock interaction. d 234U0 indicates pedogenic intensity of soil profile above the cave and sensitively reflects alternations of pedogenesis and aeolian accumulation processes of Xiashu loess in Nanjing. Consequently, uranium concentration and its isotope ratio in stalagmites may provide a new proxy for climate change. 相似文献
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本文通过论述部分运动竞赛项目,在比赛中教练员与场内运动员及运动员之间的相互沟通的形式和方法,运用实例分析,说明手语指挥在运动竞赛中的可行性及其作用。 相似文献
269.
Tectonic affinity of Paleozoic stratigraphic slices along the northern margin in Dabie Orogen, central China: evidence from Pb isotope of rocks 总被引:5,自引:0,他引:5
Metavolcanic and metasedimentary rocks from the Paleozoic tectono-stratigraphic units along the northern margin in the Dabie orogen show that there are two types of Pb isotopic compositions, which have some affined regularity with tectonic subdivision. Compared with the main tectonic units of the Qinling orogen, the Dingyuan Formation should be the part of the South Qinling orogenic belt or the northern margin of the Yangtze craton, characterized by less radiogenic Pb isotopic composition, and the Guishan Formation, Nanwan Formation-Foziling Group and the Carboniferous should be the part of the North Qinling orogenic belt which is extended to the east, characterized by more radiogenic Pb isotopic composition. These facts combined with the distribution of the geological units suggest that the Paleozoic subduction zone between the Yangtze and North China cratons should be located in the north boundary of the Nanwan Formation-Foziling Group or somewhere that is covered by the Nanwan Formation-Foziling Group now. From the Pb isotopic evidence and suggestion presented here, one aspect of the constraint is provided for determining the position of the Triassic collision suture between the two cratons. 相似文献
270.
The violaxanthin de-epoxidase gene was cloned from rice (Oryza sauva subsp japonica). The full length of the cDNA is 1887 bp, encoding a 446-amino acids protein with the transit peptide of 98 amino acids. The
bacterial expression vector pET-Rvde was constructed and the expression quantity of the exogenous protein increased with the
induction time by 0.4 mmol/L IPTG. Its molecular weight was similar with that of the native VDE. Western blotting indicated
that the expressed protein has immunological reaction with the VDE polyclonal antibody. The absorbance spectrum together with
xanthophyll pigments quantification by HPLC demonstrated that the expressed VDE has its enzyme activity, which can de-epoxidate
violaxanthin into antheraxanthin and zeaxanthin in vitro. 相似文献