Linkers of Cell Polarity and Cell Cycle Regulation in the Fission Yeast Protein Interaction Network

The study of gene and protein interaction networks has improved our understanding of the multiple, systemic levels of regulation found in eukaryotic and prokaryotic organisms. Here we carry out a large-scale analysis of the protein-protein interaction (PPI) network of fission yeast (Schizosaccharomyces pombe) and establish a method to identify ‘linker’ proteins that bridge diverse cellular processes - integrating Gene Ontology and PPI data with network theory measures. We test the method on a highly characterized subset of the genome consisting of proteins controlling the cell cycle, cell polarity and cytokinesis and identify proteins likely to play a key role in controlling the temporal changes in the localization of the polarity machinery. Experimental inspection of one such factor, the polarity-regulating RNB protein Sts5, confirms the prediction that it has a cell cycle dependent regulation. Detailed bibliographic inspection of other predicted ‘linkers’ also confirms the predictive power of the method. As the method is robust to network perturbations and can successfully predict linker proteins, it provides a powerful tool to study the interplay between different cellular processes.

对基因与蛋白质相互作用网络的研究，加深了我们对真核与原核生物中多层系统性调控机制的认知。本研究针对裂殖酵母（Schizosaccharomyces pombe）的蛋白质相互作用（protein-protein interaction, PPI）网络开展大规模分析，并构建了一种可识别连接不同细胞过程的‘衔接蛋白’的方法：该方法将基因本体（Gene Ontology）数据、PPI数据与网络理论度量指标相结合。我们以基因组中一组经过充分注释的子集为测试对象，该子集涵盖调控细胞周期、细胞极性与胞质分裂的蛋白质，借此识别出可能在调控极性调控系统定位的时序变化中发挥关键作用的蛋白质。我们对其中一个候选因子——调控极性的RNB蛋白Sts5进行实验验证，证实其存在细胞周期依赖性调控，与此前的预测相符。对其余预测得到的‘衔接蛋白’开展详细文献调研后，同样验证了本方法的预测能力。鉴于该方法对网络扰动具有鲁棒性且可有效预测衔接蛋白，其为研究不同细胞过程间的串扰关系提供了强有力的工具。