One of the most fundamental challenges in biology is to understand how cells process and integrate information from different signaling pathways into coordinated physiological responses. Importantly, cellular signaling needs to ensure the proper coordination of metabolism with growth and cell division, in response to environmental or hormonal cues. Yet, we currently only have a poor and mostly phenomenological understanding of how metabolism and the cell division cycle are linked.
In the model organism budding yeast we have recently shown that hundreds of metabolites oscillate during the cell cycle. This is partially driven by Cdk1, the main cell cycle kinase in yeast. We are currently using phosphoproteomics, in vivo biochemistry and live cell imaging to further understand the global coordination of metabolism and proliferation. We find that many metabolic regulators such as proteins of the PKA- and PP1-pathways are phospho-regulated during the cell cycle. This may explain how CDK and other cell cycle kinases indirectly control metabolism to support cell cycle progression. In turn, we find evidence that metabolic regulators like nutrient sensing pathways impinge on cell cycle progression and can delay or arrest any cell cycle phase. In summary, our data suggests that metabolic and cell cycle regulation are much more tightly and directly coordinated than previously appreciated.