Abstract
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.
Highlights
The eukaryotic cell cycle is one of the most important and evolutionary conserved processes of cells [1,2]
We investigate by graph theoretical network analysis approaches the protein-protein interaction network of fission yeast, and present a new network measure, linkerity, that predicts the ability of certain proteins to function as bridges between diverse cellular processes
In depth literature analysis confirms that several proteins identified as linkers of cell polarity regulation are associated with cell cycle and/ or cell division control
Summary
The eukaryotic cell cycle is one of the most important and evolutionary conserved processes of cells [1,2]. The cell cycle integrates signals from multiple pathways to control tissue growth and homeostasis in multicellular organisms, as well as reproduction and proliferation in single cell organisms [3]. The cell cycle regulates and is regulated by other key processes such as DNA replication, cytokinesis and cell growth [4,5,6,7,8,9]. Because of the well-characterized interactions between the cell cycle and other processes in the fission yeast Schizosaccharomyces pombe, we focus our analysis on this organism, where these processes have not yet been investigated yet by protein interaction network analysis methods
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