Current perspective on the regulation of FOXO4 and its role in disease progression

Cell Mol Life Sci. 2020 Feb;77(4):651-663. doi: 10.1007/s00018-019-03297-w. Epub 2019 Sep 16.

Abstract

Forkhead box O4 (FOXO4) is a member of the FOXO family that regulates a number of genes involved in metabolism, cell cycle, apoptosis, and cellular homeostasis via transcriptional activity. It also mediates cell responses to oxidative stress and treatment with antitumor agents. The expression of FOXO4 is repressed by microRNAs in multiple cancer cells, while FOXO4 function is regulated by post-translational modifications and interaction with other proteins. The deregulation of FOXO4 is closely linked to the progression of several types of cancer, senescence, and other diseases. In this review, we present recent findings on the regulation of FOXO4 in physiological and pathological conditions and provide an overview of the complex role of FOXO4 in disease development and response to therapy.

Keywords: Apoptosis; Cancer; Cell proliferation; Drug response; FOXO4.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Cell Cycle Proteins / analysis
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Proliferation
  • Disease Progression
  • Forkhead Transcription Factors / analysis
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Oxidative Stress
  • Protein Interaction Maps
  • Protein Processing, Post-Translational
  • Transcriptional Activation

Substances

  • Cell Cycle Proteins
  • FOXO4 protein, human
  • Forkhead Transcription Factors