FOXO transcription factors: key regulators of cellular quality control

Trends Biochem Sci. 2014 Apr;39(4):159-69. doi: 10.1016/j.tibs.2014.02.003. Epub 2014 Mar 13.


FOXO transcription factors are conserved regulators of longevity downstream of insulin signaling. These transcription factors integrate signals emanating from nutrient deprivation and stress stimuli to coordinate programs of genes involved in cellular metabolism and resistance to oxidative stress. Here, we discuss emerging evidence for a pivotal role of FOXO factors in promoting the expression of genes involved in autophagy and the ubiquitin-proteasome system--two cell clearance processes that are essential for maintaining organelle and protein homeostasis (proteostasis). The ability of FOXO to maintain cellular quality control appears to be critical in processes and pathologies where damaged proteins and organelles accumulate, including aging and neurodegenerative diseases.

Keywords: FOXO transcription factors; aging; cellular quality control; proteostasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aging / metabolism
  • Aging / pathology
  • Animals
  • Autophagy
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • Proteasome Endopeptidase Complex
  • Proteolysis*
  • Ubiquitin
  • Ubiquitin-Protein Ligases / metabolism


  • Forkhead Transcription Factors
  • Ubiquitin
  • Ubiquitin-Protein Ligases
  • Proteasome Endopeptidase Complex