Nutritional Control of Cell Size by the Greatwall-Endosulfine-PP2A·B55 Pathway

Curr Biol. 2016 Feb 8;26(3):319-30. doi: 10.1016/j.cub.2015.12.035. Epub 2016 Jan 14.


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.

Keywords: B55; Igo1; PP2A; Ppk18; S. pombe; TOR; cell cycle; cell size; endosulfine; greatwall.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / metabolism
  • Cell Cycle*
  • Intercellular Signaling Peptides and Proteins
  • Mechanistic Target of Rapamycin Complex 1
  • Multiprotein Complexes / metabolism
  • Nutritional Physiological Phenomena*
  • Peptides / metabolism
  • Schizosaccharomyces / physiology*
  • Schizosaccharomyces pombe Proteins / metabolism
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism


  • Cell Cycle Proteins
  • Intercellular Signaling Peptides and Proteins
  • Multiprotein Complexes
  • Peptides
  • Schizosaccharomyces pombe Proteins
  • endosulfine
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases