Browsing by Author "Csikasz-Nagy, Attila"
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- Cell cycle regulation by feed-forward loops coupling transcription and phosphorylationCsikasz-Nagy, Attila; Kapuy, Orsolya; Toth, Attila; Pal, Csaba; Jensen, Lars Juhl; Uhlmann, Frank; Tyson, John J.; Novak, Bela (Nature Publishing Group, 2009-01-01)The eukaryotic cell cycle requires precise temporal coordination of the activities of hundreds of ‘executor’ proteins (EPs) involved in cell growth and division. Cyclin-dependent protein kinases (Cdks) play central roles in regulating the production, activation, inactivation and destruction of these EPs. From genome-scale data sets of budding yeast, we identify 126 EPs that are regulated by Cdk1 both through direct phosphorylation of the EP and through phosphorylation of the transcription factors that control expression of the EP, so that each of these EPs is regulated by a feed-forward loop (FFL) from Cdk1. By mathematical modelling, we show that such FFLs can activate EPs at different phases of the cell cycle depending of the effective signs (+ or -) of the regulatory steps of the FFL.We provide several case studies of EPs that are controlled by FFLs exactly as our models predict. The signal-transduction properties of FFLs allow one (or a few) Cdk signal(s) to drive a host of cell cycle responses in correct temporal sequence.
- The critical size is set at a single-cell level by growth rate to attain homeostasis and adaptationFerrezuelo, Francisco; Colomina, Neus; Palmisano, Alida; Gari, Eloi; Gallego, Carme; Csikasz-Nagy, Attila; Aldea, Marti (Springer Nature, 2012-08)Budding yeast cells are assumed to trigger Start and enter the cell cycle only after they attain a critical size set by external conditions. However, arguing against deterministic models of cell size control, cell volume at Start displays great individual variability even under constant conditions. Here we show that cell size at Start is robustly set at a single-cell level by the volume growth rate in G1, which explains the observed variability. We find that this growth-rate-dependent sizer is intimately hardwired into the Start network and the Ydj1 chaperone is key for setting cell size as a function of the individual growth rate. Mathematical modelling and experimental data indicate that a growth-rate-dependent sizer is sufficient to ensure size homeostasis and, as a remarkable advantage over a rigid sizer mechanism, it reduces noise in G1 length and provides an immediate solution for size adaptation to external conditions at a population level.
- Time-keeping and decision-making in living cells: Part ITyson, John J.; Csikasz-Nagy, Attila; Gonze, Didier; Kim, Jae Kyoung; Santos, Silvia; Wolf, Jana (Royal Society, 2022-04-15)To survive and reproduce, a cell must process information from its environment and its own internal state and respond accordingly, in terms of metabolic activity, gene expression, movement, growth, division and differentiation. These signal-response decisions are made by complex networks of interacting genes and proteins, which function as biochemical switches and clocks, and other recognizable information-processing circuitry. This theme issue of Interface Focus (in two parts) brings together articles on time-keeping and decision-making in living cells-work that uses precise mathematical modelling of underlying molecular regulatory networks to understand important features of cell physiology. Part I focuses on time-keeping: mechanisms and dynamics of biological oscillators and modes of synchronization and entrainment of oscillators, with special attention to circadian clocks.
- Time-keeping and decision-making in living cells: Part IITyson, John J.; Csikasz-Nagy, Attila; Gonze, Didier; Kim, Jae Kyoung; Santos, Silvia; Wolf, Jana (Royal Society, 2022-06-10)