A proteomic screen reveals SCF^Grr1 targets that regulate the glycolytic–gluconeogenic switch

Jennifer A. Benanti et al, Nature Cell Biology. 2007

Speaker：傅孝瑜                 Time: 2008/03/26 13:10~14:00

Commentator：張權發 老師        Place: Room601

Abstract：

Glycolysis and gluconeogenesis are two major carbohydrate metabolism pathways used by cells for effective energy usage. These pathways are regulated reciprocally by intercellular and intracellular signals and they do not take place simultaneously in the same cell to a significant extent. The Saccharomyces cerevisiae protein Grr1 is a nonessential F-box protein which is the substrate recognition component of the Skp1–Cul1–F-box-protein (SCF) E3 ubiquitin ligase with important role in many mammalian functions.⁽¹⁾ It is not only a glucose sensor⁽²⁾ but also a regulator of cell cycle⁽³⁾. In order to understand better how SCF^Grr1 coordinates cell cycle regulation with nutrient availability, the authors developed a proteomic screening method that used high-throughput quantitative microscopy screening comprehensively for substrates of SCF^Grr1. Two of the seven new candidates, Tye7 and Pfk27 were recruited in the glycolytic-gluconeogenic switch model. In this model, Pfk27 is phosphorylatedby the protein kinase Snf1 in the absence of glucose, then degraded by SCF^Grr1. Pfk27 turnover reduces levels of the glycolytic activator/gluconeogenic inhibitor fructose-2,6-bisphosphate. These findings indicate that SCF^Grr1 plays an important role in the glycolytic–gluconeogenic switch mechanism.

References：

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