Coupling TOR to the Cell Cycle by the Greatwall-Endosulfine-PP2A-B55 Pathway

Biomolecules. 2017 Aug 4;7(3):59. doi: 10.3390/biom7030059.


Cell growth and division are two processes tightly coupled in proliferating cells. While Target of Rapamycin (TOR) is the master regulator of growth, the cell cycle is dictated by the activity of the cyclin-dependent kinases (CDKs). A long-standing question in cell biology is how these processes may be connected. Recent work has highlighted that regulating the phosphatases that revert CDK phosphorylations is as important as regulating the CDKs for cell cycle progression. At mitosis, maintaining a low level of protein phosphatase 2A (PP2A)-B55 activity is essential for CDK substrates to achieve the correct level of phosphorylation. The conserved Greatwall-Endosulfine pathway has been shown to be required for PP2A-B55 inhibition at mitosis in yeasts and multicellular organisms. Interestingly, in yeasts, the Greatwall-Endosulfine pathway is negatively regulated by TOR Complex 1 (TORC1). Moreover, Greatwall-Endosulfine activation upon TORC1 inhibition has been shown to regulate the progression of the cell cycle at different points: the G1 phase in budding yeast, the G2/M transition and the differentiation response in fission yeast, and the entry into quiescence in both budding and fission yeasts. In this review, we discuss the recent findings on how the Greatwall-Endosulfine pathway may provide a connection between cell growth and the cell cycle machinery.

Keywords: Endosulfine; Greatwall; PP2A-B55; TOR; cell cycle; cell growth.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Cycle
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Mechanistic Target of Rapamycin Complex 1 / metabolism
  • Mechanistic Target of Rapamycin Complex 2 / metabolism
  • Microtubule-Associated Proteins / metabolism*
  • Peptides / metabolism*
  • Protein Phosphatase 2 / metabolism*
  • Saccharomycetales / metabolism
  • Schizosaccharomyces / growth & development
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / metabolism


  • Intercellular Signaling Peptides and Proteins
  • Microtubule-Associated Proteins
  • Peptides
  • Schizosaccharomyces pombe Proteins
  • endosulfine
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2
  • Protein Phosphatase 2