The multifaceted role of cell cycle regulators in the coordination of growth and metabolism

FEBS J. 2021 Jun;288(12):3813-3833. doi: 10.1111/febs.15586. Epub 2020 Oct 25.

Abstract

Adapting to changes in nutrient availability and environmental conditions is a fundamental property of cells. This adaptation requires a multi-directional coordination between metabolism, growth, and the cell cycle regulators (consisting of the family of cyclin-dependent kinases (CDKs), their regulatory subunits known as cyclins, CDK inhibitors, the retinoblastoma family members, and the E2F transcription factors). Deciphering the mechanisms accountable for this coordination is crucial for understanding various patho-physiological processes. While it is well established that metabolism and growth affect cell division, this review will focus on recent observations that demonstrate how cell cycle regulators coordinate metabolism, cell cycle progression, and growth. We will discuss how the cell cycle regulators directly regulate metabolic enzymes and pathways and summarize their involvement in the endolysosomal pathway and in the functions and dynamics of mitochondria.

Keywords: cell cycle regulators; cell growth; endolysosomes; metabolism; mitochondria.

Publication types

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

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Cell Cycle / drug effects
  • Cell Cycle / genetics*
  • Cells, Cultured
  • Cyclin-Dependent Kinase Inhibitor Proteins / genetics*
  • Cyclin-Dependent Kinase Inhibitor Proteins / metabolism
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Cyclin-Dependent Kinases / genetics*
  • Cyclin-Dependent Kinases / metabolism
  • Cyclins / genetics*
  • Cyclins / metabolism
  • E2F Transcription Factors / genetics
  • E2F Transcription Factors / metabolism
  • Endosomes / drug effects
  • Endosomes / metabolism
  • Gene Expression Regulation
  • Humans
  • Lysosomes / drug effects
  • Lysosomes / metabolism
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Nutritive Value / physiology*
  • Protein Kinase Inhibitors / pharmacology
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism
  • Signal Transduction

Substances

  • Cyclin-Dependent Kinase Inhibitor Proteins
  • Cyclins
  • E2F Transcription Factors
  • Protein Kinase Inhibitors
  • Retinoblastoma Protein
  • Cyclin-Dependent Kinases