Cell cycle and death control: long live Forkheads

Trends Biochem Sci. 2002 Jul;27(7):352-60. doi: 10.1016/s0968-0004(02)02113-8.


The FOXO family of Forkhead transcription factors, FKHR (FOXO1), FKHR-L1 (FOXO3a) and AFX (FOXO4), are regulated by the phosphoinositide-3-kinase-protein-kinase-B (PI3K-PKB/c-Akt) pathway. Direct phosphorylation by PKB results in cytoplasmic retention and inactivation, inhibiting the expression of FOXO-regulated genes, which control the cell cycle, cell death, cell metabolism and oxidative stress. This pathway appears to be well conserved throughout evolution. In the nematode Caenorhabditis elegans, it affects lifespan and controls dauer formation. Recent discoveries about FOXO regulation by PI3K-PKB signalling suggest that the PI3K-PKB-FOXO pathway might participate in similar processes in higher eukaryotes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Caenorhabditis elegans / physiology
  • Cell Cycle / physiology*
  • Cell Death / physiology*
  • Cell Transformation, Neoplastic
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation
  • Humans
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Signal Transduction / physiology*
  • Transcription Factors / metabolism*


  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Transcription Factors
  • Phosphatidylinositol 3-Kinases
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt