Proteomics
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Each phase of eukaryotic cell cycle is tightly controlled by multicomponent regulatory networks based on complex relationships of protein phosphorylation. In order to better understand the relationships between kinases and their substrate proteins during the progression of cell cycle, we analyzed phosphoproteome of HeLa cells during G1, S, and G2/M phases of cell cycle using our developed quantitative phosphoproteomic approaches. A total of 4776 high-confidence phosphorylation sites (phosphosites) in 1177 proteins were identified. ⋯ Further analyses showed that approximately half of the examined two phosphosite combinations were correlatively regulated, regardless of whether the kinase groups were same or not. In general, the majority of proteins containing correlated phosphosites had solely co-regulated or counter-regulated phosphosites, and co-regulation was significantly more frequent than counter-regulation, suggesting that the former may be more important for regulating the cell cycle. In conclusion, our findings provide new insights into the complex regulatory mechanisms of protein phosphorylation networks during eukaryotic cell cycle.