Role of Forkhead Box O (FOXO) transcription factor in aging and diseases

Gene. 2018 Mar 30:648:97-105. doi: 10.1016/j.gene.2018.01.051. Epub 2018 Feb 4.

Abstract

Fork head box O (FOXO) transcription factor is a key player in an evolutionarily conserved pathway. The mammalian FOXO family consists of FOXO1, 3, 4 and 6, are highly similar in their structure, function and regulation. To maintain optimum body function, the organisms have developed complex mechanisms for homeostasis. Importantly, it is well known that when these mechanisms dysregulate it results in the development of age-related disease. FOXO proteins are involved in a diverse cellular function and also have clinical significance including cell cycle arrest, cell differentiation, tumour suppression, DNA repair, longevity, diabetic complications, immunity, wound healing, regulation of metabolism and thus treatment of several types of diseases. By the combinations of post-translational modifications FOXO's serve as a 'molecular code' to sense external stimuli and recruit it as to specific regions of the genome and provide an integrated cellular response to changing physiological conditions. Akt/Protein kinase B a signaling pathway as a main regulator of FOXO to perform a diverse function in organisms. The present review summarizes the molecular and clinical aspects of FOXO transcription factor. And also elaborate the interaction of FOXO with the nucleosome remodelling complex to target genes, which is essential to cellular homeostasis.

Keywords: Age related disease; Aging; Akt; FOXO; Forkhead box.

Publication types

  • Review

MeSH terms

  • Aging / genetics*
  • Aging / metabolism
  • Animals
  • Cell Physiological Phenomena / genetics
  • Disease / genetics*
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation*
  • Humans
  • Longevity / genetics
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Signal Transduction / genetics

Substances

  • Forkhead Transcription Factors
  • Protein Isoforms