title: Nutritional Control of Cell Size by the Greatwall-Endosulfine-PP2A·B55 Pathway.
abstract: Proliferating cells adjust their cell size depending on the nutritional environment. Cells are large in rich media and small in poor media. This physiological response has been demonstrated in both unicellular and multicellular organisms. Here we show that the greatwall-endosulfine (Ppk18-Igo1 in fission yeast) pathway couples the nutritional environment to the cell-cycle machinery by regulating the activity of PP2A·B55. In the presence of nutrients, greatwall (Ppk18) protein kinase is inhibited by TORC1 and PP2A·B55 is active. High levels of PP2A·B55 prevent the activation of mitotic Cdk1·Cyclin B, and cells increase in size in G2 before they undergo mitosis. When nutrients are limiting, TORC1 activity falls off, and the activation of greatwall (Ppk18) leads to the phosphorylation of endosulfine (Igo1) and inhibition of PP2A·B55, which in turn allows full activation of Cdk1·CyclinB and entry into mitosis with a smaller cell size. Given the conservation of this pathway, it is reasonable to assume that this mechanism operates in higher eukaryotes, as well.
authors.affiliation: Instituto de Biología Funcional y Genómica, CSIC/University of Salamanca, 37007 Salamanca, Spain.
authors.forename: Nathalia
authors.initials: N
authors.lastname: Chica
authors.affiliation: Instituto de Biología Funcional y Genómica, CSIC/University of Salamanca, 37007 Salamanca, Spain.
authors.forename: Ana Elisa
authors.initials: AE
authors.lastname: Rozalén
authors.affiliation: Instituto de Biología Funcional y Genómica, CSIC/University of Salamanca, 37007 Salamanca, Spain.
authors.forename: Livia
authors.initials: L
authors.lastname: Pérez-Hidalgo
authors.affiliation: Instituto de Biología Funcional y Genómica, CSIC/University of Salamanca, 37007 Salamanca, Spain.
authors.forename: Angela
authors.initials: A
authors.lastname: Rubio
authors.affiliation: Oxford Centre for Integrative Systems Biology, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Bela
authors.initials: B
authors.lastname: Novak
authors.affiliation: Instituto de Biología Funcional y Genómica, CSIC/University of Salamanca, 37007 Salamanca, Spain. Electronic address: smo@usal.es.
authors.forename: Sergio
authors.initials: S
authors.lastname: Moreno
mesh_terms: D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism; D009747:Nutritional Physiological Phenomena; D010455:Peptides / Q000378:metabolism; D012568:Schizosaccharomyces / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D036341:Intercellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D010455:Peptides; D029702:Schizosaccharomyces pombe Proteins; C075663:endosulfine; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: B55; Igo1; PP2A; Ppk18; S. pombe; TOR; cell cycle; cell size; endosulfine; greatwall