CDK1, the Other 'Master Regulator' of Autophagy

Trends Cell Biol. 2021 Feb;31(2):95-107. doi: 10.1016/j.tcb.2020.11.001. Epub 2020 Nov 30.

Abstract

Autophagy and cap-dependent mRNA translation are tightly regulated by the mechanistic target of rapamycin complex 1 (mTORC1) signalling complex in response to nutrient availability. However, the regulation of these processes, and mTORC1 itself, is different during mitosis, and this has remained an area of significant controversy; for example, studies have argued that autophagy is either repressed or highly active during mitosis. Recent studies have shown that autophagy initiation is repressed, and cap-dependent mRNA translation is maintained during mitosis despite mTORC1 activity being repressed. This is achieved in large part by a switch from mTORC1- to cyclin-dependent kinase 1 (CDK1)-mediated regulation. Here, we review the history and recent advances and seek to present a unifying model to inform the future study of autophagy and mTORC1 during mitosis.

Keywords: CDK1; autophagy; mTORC1; mitosis; translation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Autophagy / physiology*
  • CDC2 Protein Kinase / metabolism*
  • Cell Line
  • Cell Line, Tumor
  • Humans
  • Mechanistic Target of Rapamycin Complex 1 / metabolism*
  • Mitosis / physiology*
  • Phosphorylation / physiology
  • Protein Biosynthesis
  • Signal Transduction / physiology

Substances

  • Mechanistic Target of Rapamycin Complex 1
  • CDC2 Protein Kinase
  • CDK1 protein, human