會(huì)員.png)
QQ交談
您所在位置：請(qǐng)輸入產(chǎn)品關(guān)鍵字：
郵編：200431
聯(lián)系人：王小姐
電話：021-56640936
傳真：021-33250231
手機(jī)：13122441390 15900755943
留言：發(fā)送留言
個(gè)性化：www.shifengsj.com
網(wǎng)址：www.shfeng-edu.com
商鋪：http://www.zjmenchuan.com/st236594/
上海士鋒生物關(guān)于長(zhǎng)壽基因的介紹
點(diǎn)擊次數(shù)：1079 發(fā)布時(shí)間：2013-6-18
據(jù)悉，科學(xué)界先前已找到與人類老化相關(guān)的基因，但卻不知這些基因如何與體內(nèi)其它物質(zhì)產(chǎn)生作用，近日中國(guó)臺(tái)灣大學(xué)（臺(tái)大）與美國(guó)約翰霍普金斯醫(yī)學(xué)院合作，證實(shí)有2種蛋白質(zhì)可調(diào)控AMPK（俗稱長(zhǎng)壽基因），研究成果對(duì)揭開了部分老化謎團(tuán)以及開發(fā)癌癥新藥帶來(lái)曙光。相關(guān)論文刊登于*生物醫(yī)學(xué)期刊《Nature》（自然）上。
該研究*作者林育誼說(shuō)，過(guò)去世界學(xué)術(shù)界僅知人體內(nèi)有2大類共數(shù)10種蛋白質(zhì)與細(xì)胞老化相關(guān)，一類是“乙酰基轉(zhuǎn)移酶”，另一類是“去乙酰酶”，人年輕時(shí)，2類蛋白質(zhì)維持能量均衡，當(dāng)年紀(jì)漸大，去乙酰酶較活化，使能量不均，進(jìn)而罹患與老化有關(guān)病癥如癌癥、高血壓等。要治療上述疾病，需要先弄清這2大類蛋白質(zhì)與其它基因的交互作用。
此次研究人員通過(guò)改良的脫氧核糖核酸干擾技術(shù)，對(duì)已知與老化相關(guān)的AMPK基因做交互作用篩檢，才發(fā)現(xiàn)有2種蛋白質(zhì)：HDAC1、p300與AMPK相關(guān)。當(dāng)HDAC1活化，AMPK會(huì)受抑制，p300則有相反作用。
這是找到可調(diào)控AMPK的蛋白質(zhì)，對(duì)解開使人老化的“去乙酰化”原因踏出一大步。該團(tuán)隊(duì)目前正在對(duì)肝癌、腸癌、甲狀腺癌等抗癌藥物進(jìn)行分析，以利研發(fā)與老化有關(guān)的癌癥治療藥物。
Functional dissection of lysine deacetylases reveals that HDAC1 and p300 regulate AMPK
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 proteins1. Acetylation of many non-histone proteins involved in chromatin, metabolism or cytoskeleton regulation were further identified in eukaryotic organisms2, 3, 4, 5, 6, but the corresponding enzymes and substrate-specific functions of the modifications are unclear. Moreover, mechanisms underlying functional specificity of individual KDACs7 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 screen8, 9, 10, 11, 12, 13 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