Growth control of the eukaryote cell: a systems biology study in yeast.
Growth control of the eukaryote cell: a systems biology study in yeast.
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DOI：
10.1186/jbiol54
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发表时间：
2007
影响因子：
--
通讯作者：
Oliver, Stephen G
中科院分区：
文献类型：
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作者：
Castrillo, Juan I;Zeef, Leo A;Hoyle, David C;Zhang, Nianshu;Hayes, Andrew;Gardner, David Cj;Cornell, Michael J;Petty, June;Hakes, Luke;Wardleworth, Leanne;Rash, Bharat;Brown, Marie;Dunn, Warwick B;Broadhurst, David;O'Donoghue, Kerry;Hester, Svenja S;Dunkley, Tom Pj;Hart, Sarah R;Swainston, Neil;Li, Peter;Gaskell, Simon J;Paton, Norman W;Lilley, Kathryn S;Kell, Douglas B;Oliver, Stephen G
细胞生长是许多关键的细胞和发育过程的基础，但对细胞生长调控的研究有限。在确定的受控条件下，转录、蛋白质组和代谢水平的全面研究目前还缺乏。代谢控制分析正被用于真核细胞的系统生物学研究。通过恒温培养，我们测量了通量(生长速率)的变化对酿酒酵母转录组、蛋白质组、内代谢组和外代谢组的影响。每个功能基因组水平都显示出与生长速度相关的明显趋势，并区分碳充足和碳有限的条件。随着生长速度的增加，持续和显着上调的基因通常是必需的，并编码进化上保守的已知功能的蛋白质，参与许多蛋白质-蛋白质相互作用。相比之下，随着生长速度的提高，更多的未知基因和更少的必需基因被下调；它们的蛋白质产物很少相互作用。在正生长速率控制下，很大一部分酵母基因与包括人类在内的其他真核生物共享同源基因。值得注意的是，编码TOR复合体(真核细胞生长的主要控制器)组成部分的基因的转录不受生长速度调节。此外，综合研究揭示了转录后调控的程度和重要性，在酶合成水平上代谢通量的控制模式，以及特定的酶反应在细胞生长过程中控制代谢通量的相关性。这项工作构成了对真核细胞生长速度控制的第一个全面的系统生物学研究。这些结果对深入研究细胞生长、体内代谢通量的调节以进行全面代谢工程以及设计真核细胞基因组规模的系统生物学模型具有直接意义。
Cell growth underlies many key cellular and developmental processes, yet a limited number of studies have been carried out on cell-growth regulation. Comprehensive studies at the transcriptional, proteomic and metabolic levels under defined controlled conditions are currently lacking. Metabolic control analysis is being exploited in a systems biology study of the eukaryotic cell. Using chemostat culture, we have measured the impact of changes in flux (growth rate) on the transcriptome, proteome, endometabolome and exometabolome of the yeast Saccharomyces cerevisiae. Each functional genomic level shows clear growth-rate-associated trends and discriminates between carbon-sufficient and carbon-limited conditions. Genes consistently and significantly upregulated with increasing growth rate are frequently essential and encode evolutionarily conserved proteins of known function that participate in many protein-protein interactions. In contrast, more unknown, and fewer essential, genes are downregulated with increasing growth rate; their protein products rarely interact with one another. A large proportion of yeast genes under positive growth-rate control share orthologs with other eukaryotes, including humans. Significantly, transcription of genes encoding components of the TOR complex (a major controller of eukaryotic cell growth) is not subject to growth-rate regulation. Moreover, integrative studies reveal the extent and importance of post-transcriptional control, patterns of control of metabolic fluxes at the level of enzyme synthesis, and the relevance of specific enzymatic reactions in the control of metabolic fluxes during cell growth. This work constitutes a first comprehensive systems biology study on growth-rate control in the eukaryotic cell. The results have direct implications for advanced studies on cell growth, in vivo regulation of metabolic fluxes for comprehensive metabolic engineering, and for the design of genome-scale systems biology models of the eukaryotic cell.