Mechanistic insights and implications of FOXO-SNAI interplay

Bioessays. 2022 Sep;44(9):e2200070. doi: 10.1002/bies.202200070. Epub 2022 Jul 13.

Abstract

Autophagy promotes both health and disease, depending on tissue types and genetic contexts, yet the regulatory mechanism remain incompletely understood. Our recent publication has uncovered a coherent FOXO-SNAI feed-forward loop in autophagy, which is evolutionarily conserved from Drosophila to human. In addition, it's revealed that DNA binding plays a critical role in intracellular localization of nucleocytoplasmic shuttling proteins. Based on these findings, herein we further integrate mechanistic insights of FOXO-SNAI regulatory interplay in autophagy and unravel the potential link of FOXO-induced autophagy with SNAI in diseases. Besides, the generality of DNA-retention mechanism on transcription factor nuclear localization is illustrated with wide-ranging discussion, and more functions potentially regulated by FOXO-SNAI feedforward loop are provided. Elucidation of these unsolved paradigms will expand the understanding of FOXO-SNAI interplay and facilitate the development of new therapeutics targeting FOXO-SNAI axis in diseases.

Keywords: DNA binding; FOXO; SNAI; autophagy; disease; feed-forward loop.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy*
  • Forkhead Transcription Factors* / genetics
  • Gene Expression Regulation
  • Humans

Substances

  • Forkhead Transcription Factors