FOXOs: signalling integrators for homeostasis maintenance

  title={FOXOs: signalling integrators for homeostasis maintenance},
  author={Astrid Eijkelenboom and Boudewijn M. T. Burgering},
  journal={Nature Reviews Molecular Cell Biology},
Forkhead box O (FOXO) transcription factors are involved in the regulation of the cell cycle, apoptosis and metabolism. In model organisms, FOXO activity also affects stem cell maintenance and lifespan as well as age-related diseases, such as cancer and diabetes. Multiple upstream pathways regulate FOXO activity through post-translational modifications and nuclear–cytoplasmic shuttling of both FOXO and its regulators. The diversity of this upstream regulation and the downstream effects of FOXOs… 
Introduction to FOXO Biology.
  • W. Link
  • Biology
    Methods in molecular biology
  • 2019
D deregulation of FOXO proteins has been shown to play an essential role in metabolic disorders, human longevity, and the suppression of tumors, providing a wealth of possibilities for restoring FOXO activity pharmaceutically.
Posttranscriptional regulation of FOXO expression: microRNAs and beyond
A brief overview on post‐transcriptional regulation of FOXO synthesis by microRNAs (miRNAs) and by RNA‐binding regulatory proteins, human antigen R (HuR) and quaking (QKI) is given.
FoxO transcription factors in cancer metabolism.
FOXO transcription factor family in cancer and metastasis
An understanding of how signalling networks integrate with the FOXO transcription factors to modulate their developmental, metabolic and tumour-suppressive functions in normal tissues and in cancer will offer a new perspective on tumorigenesis and metastasis, and open up therapeutic opportunities for malignant diseases.
Multifaceted functions of the forkhead box transcription factors FoxO1 and FoxO3 in skin.
Foxo transcription factors in T cell biology and tumor immunity.
Critical physiological and pathological functions of Forkhead Box O tumor suppressors
A better understanding of the structure and critical functions of FOXO transcription factors and tumor suppressors may contribute to the development of novel therapies for cancer and other diseases.
FOXO transcription factors in antioxidant defense
An overview is provided on the contribution of FOXO target genes to cellular antioxidative strategies, and on the impact of thiol homeostasis and thiol modification on FOXO activity.
FOXO transcription factors at the interface of metabolism and cancer
There is emerging evidence that deregulation of FOXO factors might account for the association between insulin resistance‐related metabolic disorders and cancer.


Stressing the role of FoxO proteins in lifespan and disease
This work has shown that a shared yet opposing regulatory network between FoxO and p53 may underlie a 'trade-off' between disease and lifespan.
The extending network of FOXO transcriptional target genes.
The functional consequences of FOXO activation are described based on the current knowledge of transcriptional targets and may provide clues to the molecular mechanisms controlling cell fate decisions.
The FoxO code
The FoxO family of Forkhead transcription factors plays an important role in longevity and tumor suppression by upregulating target genes involved in stress resistance, metabolism, cell cycle arrest and apoptosis and an intriguing possibility is that FoxO PTMs may act as a ‘molecular FoxO code’ read by selective protein partners to rapidly regulate gene-expression programs.
Stress-Dependent Regulation of FOXO Transcription Factors by the SIRT1 Deacetylase
One way in which members of the Sir2 family of proteins may increase organismal longevity is by tipping FOXO-dependent responses away from apoptosis and toward stress resistance.
FOXO3a regulates reactive oxygen metabolism by inhibiting mitochondrial gene expression
Analysis of the transcriptional programme induced in response to Forkhead-box protein O3a (FOXO3a) activation suggests that FOXO factors regulate mitochondrial activity through inhibition of c-Myc function and alter the hypoxia response.
FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP
It is shown that FOXO becomes monoubiquitinated in response to increased cellular oxidative stress, resulting in its re-localization to the nucleus and an increase in its transcriptional activity.
O-GlcNAc Regulates FoxO Activation in Response to Glucose*
It is shown that O-GlcNAc on hepatic FoxO1 is increased in diabetes, resulting in the paradoxically increased expression of gluconeogenic genes while concomitantly inducing expression of genes encoding enzymes that detoxify reactive oxygen species.
Highly specialized role of Forkhead box O transcription factors in the immune system.
This review will focus on the recent advances made in the understanding of the many ways that Foxo factors regulate the immune system, including a discussion of how the specialized versus redundant functions of Foxo transcription factors impact immune system homeostasis.