德國(guó)馬普生物化學(xué)研究所和丹麥哥本哈根大學(xué)的研究人員發(fā)現(xiàn),，人體蛋白質(zhì)化學(xué)組分中的醋酸根對(duì)人體細(xì)胞的變化有很大影響，不管是細(xì)胞分裂,，還是DNA遺傳,，或是細(xì)胞老化過(guò)程，醋酸根都起著分子開(kāi)關(guān)的作用,。這一發(fā)現(xiàn)將對(duì)開(kāi)發(fā)治療癌癥,、老年癡呆癥和帕金森氏病藥物有重要意義，該項(xiàng)研究成果已被刊登在最新一期的美國(guó)《科學(xué)》雜志上,。
研究人員發(fā)現(xiàn),，蛋白質(zhì)分子與醋酸根的結(jié)合，可以控制蛋白質(zhì)特定功能的開(kāi)啟或關(guān)閉,，而通過(guò)特定化學(xué)酶的乙?；饔茫姿岣梢耘c蛋白質(zhì)分子分開(kāi),，這一可逆過(guò)程對(duì)細(xì)胞的許多變化起著決定性的作用,。德國(guó)馬普生物化學(xué)所的研究人員利用他們自己開(kāi)發(fā)的新技術(shù)，首次對(duì)蛋白質(zhì)與醋酸根的結(jié)合,，及整個(gè)蛋白質(zhì)分子開(kāi)關(guān)的過(guò)程狀態(tài)進(jìn)行了檢測(cè),，在約1800個(gè)蛋白質(zhì)中總共發(fā)現(xiàn)超過(guò)3600個(gè)分子開(kāi)關(guān)節(jié)點(diǎn),，并發(fā)現(xiàn)蛋白質(zhì)乙酰化的能力遠(yuǎn)遠(yuǎn)超過(guò)迄今的想象,。
研究人員過(guò)去認(rèn)為,，蛋白質(zhì)的乙酰化對(duì)細(xì)胞核的基因調(diào)節(jié)只起到一定的作用,，而最新的研究結(jié)果顯示：所有的細(xì)胞變化過(guò)程都與此有關(guān),，例如細(xì)胞分裂、DNA信息的遺傳或DNA的修補(bǔ),。沒(méi)有乙?；?xì)胞就喪失功能,。使蛋白質(zhì)乙?；氖歉鞣N酶，例如Cdc28,，這種酶對(duì)酵母細(xì)胞的分裂是必須的,，沒(méi)有這種酶的參與，乙酰開(kāi)關(guān)就無(wú)法工作,，酵母細(xì)胞就會(huì)死亡,。
蛋白質(zhì)調(diào)節(jié)功能的缺損是導(dǎo)致許多疾病的根源，因此,，利用蛋白質(zhì)乙?；黹_(kāi)發(fā)新藥具有重要的意義，特別是治療癌癥的藥物,。丹麥哥本哈根大學(xué)的研究人員認(rèn)為另一重要的應(yīng)用領(lǐng)域是治療老年性疾病,，如老年癡呆癥和帕金森氏病。雖然蛋白質(zhì)乙?；谏锖团R床醫(yī)學(xué)上有重要意義,，但研究人員對(duì)活細(xì)胞的乙酰化過(guò)程還了解甚少,，借助于這項(xiàng)最新的研究成果,，研究人員可以對(duì)乙酰開(kāi)關(guān)的功效有更全面的認(rèn)識(shí)，并將極大地促進(jìn)相關(guān)新藥的開(kāi)發(fā),。（生物谷Bioon.com）
生物谷推薦原始出處：
Science 14 August 2009:DOI: 10.1126/science.1175371
Lysine Acetylation Targets Protein Complexes and Co-Regulates Major Cellular Functions
Chunaram Choudhary,1,2 Chanchal Kumar,1 Florian Gnad,1 Michael L. Nielsen,1,2 Michael Rehman,3 Tobias C. Walther,3 Jesper V. Olsen,1,2 Matthias Mann1,2,*
Lysine acetylation is a reversible posttranslational modification of proteins and plays a key role in regulating gene expression. Technological limitations have so far prevented a global analysis of lysine acetylation’s cellular roles. We used high-resolution mass spectrometry to identify 3600 lysine acetylation sites on 1750 proteins and quantified acetylation changes in response to the deacetylase inhibitors suberoylanilide hydroxamic acid and MS-275. Lysine acetylation preferentially targets large macromolecular complexes involved in diverse cellular processes, such as chromatin remodeling, cell cycle, splicing, nuclear transport, and actin nucleation. Acetylation impaired phosphorylation-dependent interactions of 14-3-3 and regulated the yeast cyclin-dependent kinase Cdc28. Our data demonstrate that the regulatory scope of lysine acetylation is broad and comparable with that of other major posttranslational modifications.
1 Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Martinsried, Germany.
2 The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
3 Organelle Architecture and Dynamics, Max Planck Institute for Biochemistry, 82152 Martinsried, Germany.
