Cyclin-Dependent Kinase Co-Ordinates Carbohydrate Metabolism and Cell Cycle in S. cerevisiae

Abstract

Summary Cyclin Dependent Kinases (CDKs) control cell division in eukaryotes by phosphorylating proteins involved in division. But successful proliferation requires co-ordination between division, and cellular growth in mass. Previous proteomic studies suggested that metabolic proteins, as well as cell division proteins, could potentially be substrates of cyclin dependent kinases. Here we focus on two metabolic enzymes of the yeast S. cerevisiae, neutral trehalase (Nth1) and glycogen phosphorylase (Gph1) and show that their activities are likely directly controlled by CDK activity, thus allowing co-ordinate regulation of carbohydrate metabolism with cell division processes. In this case, co-ordinate regulation may optimize the decision to undertake a final cell division as nutrients are being exhausted. Co-regulation of cell division processes and metabolic processes by CDK activity may be a general phenomenon important for co-ordinating the cell cycle with growth.

Advances and challenges in logical modeling of cell cycle regulation: perspective for multi-scale, integrative yeast cell models

“…2016; Zhao et al. 2016) and in mammalian cells (Lim and Kaldis 2013; Kaplon, van Dam and Peeper 2015). Building a new cell is dependent on a number of metabolic and biosynthetic reactions which impact on cellular growth, e.g.…”

“…2016; Zhao et al. 2016). Since in vitro experiments suggested a Clb2/Cdk1-mediated phosphorylation of the trehalase Nth1, an activatory effect of Clb2 on Nth1 was simulated, as shown in Fig.…”

Coupling of the cell cycle and metabolism in yeast cell-cycle-related oscillations via resource criticality and checkpoint gating

“…For instance, Zhao, Chen, Carey, and Futcher (2016) and Ewald, Kuehne, Zamboni, and Skotheim (2016) note that the CDC and metabolism have many regulatory genes in common. Additionally, understanding yeast oscillations and regulation of metabolism is important in the efficient management of bioprocesses (Beuse, Kopmann, Diekmann, & Thoma, 1999;Uchiyama, Morimoto, Yokoyama, & Shioya, 1996).…”

“…Detailed biochemical models of the growth and division processes within a single fission yeast's cell cycle, including checkpoint controls, were considered in Novak, Csikasz-Nagy, Gyorffy, Chen, and Tyson (1998). Recently, Zhao et al (2016) and Ewald et al (2016) observed that the use of internal carbohydrates is regulated by CDK activity. CDKs have long been known to be primary regulatory agents in the cell cycle.…”

What is the main mechanism of the origin of phosphorylation sites? Still an open question

“…It is a very intriguing and sound, intuitively plausible hypothesis that provides good insights into the evolution of phosphorylation sites and was approved by many researchers in the following years (Nishino et al, 2013;Fleurie et al, 2014;Rocha et al, 2014;Chang et al, 2016;Seaman et al, 2016;Zhao et al, 2016). However, there are still some issues that need to be clarified further.…”