生物谷報(bào)道:日本科學(xué)家近日研究發(fā)現(xiàn),當(dāng)細(xì)胞中能量減少時(shí),,一種名為eNoSC的蛋白質(zhì)聯(lián)合體能夠減慢蛋白質(zhì)的生產(chǎn),。這對(duì)于細(xì)胞存活具有關(guān)鍵作用,缺乏這一聯(lián)合體組分的缺能細(xì)胞會(huì)快速自我破壞,。相關(guān)論文發(fā)表在《細(xì)胞》(Cell)雜志上,。
蛋白質(zhì)由核糖體建造,之前的研究表明,,核糖體RNA(rRNA)基因的表達(dá)部分是由組蛋白的化學(xué)變化調(diào)節(jié)的,。
在最新的研究中,日本筑波大學(xué)的Junn Yanagisawa和同事鑒別出了eNoSC,,正是它造成了這些化學(xué)變化,。
eNoSC包含三種蛋白,其中之一為SIRT1,。研究人員認(rèn)為,,SIRT1在細(xì)胞應(yīng)付能量減少過程中發(fā)揮了作用。eNoSC減少了葡萄糖缺乏細(xì)胞中rRNA的生產(chǎn),,為能量缺乏時(shí)減慢蛋白質(zhì)生產(chǎn)提供了新方式,。
更進(jìn)一步,研究人員發(fā)現(xiàn),,當(dāng)eNoSC三種蛋白中任意一種的生產(chǎn)被抑制時(shí),,葡萄糖缺乏的細(xì)胞會(huì)更快地死亡。
美國(guó)麻省大學(xué)醫(yī)學(xué)院的Janet Stein認(rèn)為,,這一發(fā)現(xiàn)“幫助我們更深入地理解能量限制怎樣調(diào)節(jié)核糖體基因表達(dá),。”不過他同時(shí)表示,此次研究是在癌細(xì)胞中進(jìn)行的,,而癌細(xì)胞本身就具有特別高的能量需求,,接下來的工作應(yīng)該是在非癌細(xì)胞中重復(fù)這一實(shí)驗(yàn)。
Yanigasawa說,,他和同事目前正在比較非癌細(xì)胞和癌細(xì)胞對(duì)能量減少的反應(yīng),。他說:“此類研究將為新型的癌癥治療策略提供基礎(chǔ),。”(科學(xué)網(wǎng) 梅進(jìn)/編譯)
生物谷推薦原始出處:
Cell, Vol 133, 627-639, 16 May 2008
Article
Epigenetic Control of rDNA Loci in Response to Intracellular Energy Status
Akiko Murayama,1,2,5,6 Kazuji Ohmori,1,6 Akiko Fujimura,1 Hiroshi Minami,4 Kayoko Yasuzawa-Tanaka,1 Takao Kuroda,1 Shohei Oie,1 Hiroaki Daitoku,2 Mitsuru Okuwaki,3 Kyosuke Nagata,3 Akiyoshi Fukamizu,2 Keiji Kimura,1 Toshiyuki Shimizu,4 and Junn Yanagisawa1,
1 Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan
2 Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan
3 Graduate School of Comprehensive Human Sciences and Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan
4 International Graduate School of Arts and Sciences, Yokohama City University, Yokohama, Kanagawa 230-0045, Japan
5 PRESTO, JST, 4-1-8 Honcho Kawaguchi, Saitama, Japan
Corresponding author
Junn Yanagisawa
[email protected]
Intracellular energy balance is important for cell survival. In eukaryotic cells, the most energy-consuming process is ribosome biosynthesis, which adapts to changes in intracellular energy status. However, the mechanism that links energy status and ribosome biosynthesis is largely unknown. Here, we describe eNoSC, a protein complex that senses energy status and controls rRNA transcription. eNoSC contains Nucleomethylin, which binds histone H3 dimethylated Lys9 in the rDNA locus, in a complex with SIRT1 and SUV39H1. Both SIRT1 and SUV39H1 are required for energy-dependent transcriptional repression, suggesting that a change in the NAD+/NADH ratio induced by reduction of energy status could activate SIRT1, leading to deacetylation of histone H3 and dimethylation at Lys9 by SUV39H1, thus establishing silent chromatin in the rDNA locus. Furthermore, eNoSC promotes restoration of energy balance by limiting rRNA transcription, thus protecting cells from energy deprivation-dependent apoptosis. These findings provide key insight into the mechanisms of energy homeostasis in cells.