FoxO transcription factors; Regulation by AKT and 14-3-3 proteins

Biochim Biophys Acta. 2011 Nov;1813(11):1938-45. doi: 10.1016/j.bbamcr.2011.06.002. Epub 2011 Jun 17.

Abstract

The forkhead box O (FoxO) transcription factor family is a key player in an evolutionary conserved pathway downstream of insulin and insulin-like growth factor receptors. The mammalian FoxO family consists of FoxO1, 3, 4 and 6, which share high similarity in their structure, function and regulation. FoxO proteins are involved in diverse cellular and physiological processes including cell proliferation, apoptosis, reactive oxygen species (ROS) response, longevity, cancer and regulation of cell cycle and metabolism. The regulation of FoxO protein function involves an intricate network of posttranslational modifications and protein-protein interactions that provide integrated cellular response to changing physiological conditions and cues. AKT was identified in early genetic and biochemical studies as a main regulator of FoxO function in diverse organisms. Though other FoxO regulatory pathways and mechanisms have been delineated since, AKT remains a key regulator of the pathway. The present review summarizes the current knowledge of FoxO regulation by AKT and 14-3-3 proteins, focusing on its mechanistic and structural aspects and discusses its crosstalk with the other FoxO regulatory mechanisms. This article is part of a Special Issue entitled: PI3K-AKT-FoxO axis in cancer and aging.

Publication types

  • Review

MeSH terms

  • 14-3-3 Proteins / metabolism*
  • Animals
  • Forkhead Box Protein O1
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • Protein Binding
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • Transcription Factors / metabolism

Substances

  • 14-3-3 Proteins
  • FOXO1 protein, human
  • FOXO3 protein, human
  • FOXO4 protein, human
  • FOXO6 protein, human
  • Forkhead Box Protein O1
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors
  • Transcription Factors
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Proto-Oncogene Proteins c-akt