Bistable switches as integrators and actuators during cell cycle progression

FEBS Lett. 2019 Oct;593(20):2805-2816. doi: 10.1002/1873-3468.13628. Epub 2019 Oct 16.

Abstract

Progression through the cell cycle is driven by bistable switches-specialized molecular circuits that govern transitions from one cellular state to another. Although the mechanics of bistable switches are relatively well understood, it is less clear how cells integrate multiple sources of molecular information to engage these switches. Here, we describe how bistable switches act as hubs of information processing and examine how variability, competition, and inheritance of molecular signals determine the timing of the Rb-E2F bistable switch that controls cell cycle entry. Bistable switches confer both robustness and plasticity to cell cycle progression, ensuring that cell cycle events are performed completely and in the correct order, while still allowing flexibility to cope with ongoing stress and changing environmental conditions.

Keywords: DNA damage; bistability; cell cycle; cell signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Cell Cycle / drug effects
  • Cell Cycle / genetics*
  • Cell Cycle Checkpoints / drug effects
  • Cell Cycle Checkpoints / genetics*
  • Cyclin-Dependent Kinases / genetics*
  • Cyclin-Dependent Kinases / metabolism
  • DNA Damage / drug effects
  • DNA Repair* / drug effects
  • DNA Replication / drug effects
  • E2F Transcription Factors / genetics*
  • E2F Transcription Factors / metabolism
  • Eukaryotic Cells / cytology
  • Eukaryotic Cells / drug effects
  • Eukaryotic Cells / metabolism
  • Gene Expression Regulation
  • Humans
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Mitogens / pharmacology
  • Retinoblastoma Protein / genetics*
  • Retinoblastoma Protein / metabolism
  • Signal Transduction

Substances

  • E2F Transcription Factors
  • Intercellular Signaling Peptides and Proteins
  • Mitogens
  • Retinoblastoma Protein
  • Cyclin-Dependent Kinases