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Extracellular Signal-Regulated Kinases: One Pathway, Multiple Fates

Xavier Deschênes-Simard1, Mohan Malleshaiah2,3, Gerardo Ferbeyre3,4

  • 1Montreal University Hospital Center (CHUM), Université de Montréal, Montréal, QC H3T 1J4, Canada.

Cancers
|January 11, 2024
PubMed

Insights

The extracellular signal-regulated kinase (ERK) pathway controls cell fate, with balanced activation promoting proliferation and survival. Understanding how ERK strength and duration dictate outcomes like cell death or differentiation is key.

Area of Science:

  • Cell Biology
  • Molecular Signaling
  • Signal Transduction

Background:

  • The Extracellular Signal-Regulated Kinase (ERK) pathway, comprising ERK1 and ERK2, is a critical regulator of cellular processes.
  • ERK signaling influences diverse cell fates including proliferation, differentiation, senescence, and cell death.
  • The precise biochemical mechanisms linking ERK activation dynamics to specific cell fates remain incompletely understood.

Purpose of the Study:

  • To review the multifaceted roles of ERK signaling in determining distinct cellular fates.
  • To explore the influence of ERK activation strength, duration, and context on cell fate outcomes.
  • To highlight the need for deciphering underlying mechanisms involving feedback, localization, protein stability, transcription factors, and chromatin.

Main Methods:

  • Comprehensive literature review of ERK signaling pathways.
  • Analysis of studies investigating the quantitative and contextual aspects of ERK activation.
  • Synthesis of current knowledge on downstream effectors and regulatory mechanisms.

Main Results:

  • ERK activation follows a 'Goldilocks principle,' where both insufficient and excessive activity impair proliferation.
  • Balanced ERK activation is generally associated with enhanced cell proliferation and survival.
  • Cell fate decisions are modulated by signaling feedback loops and the spatial context of ERK activation.

Conclusions:

  • The degree of ERK activation is a critical determinant of cell fate.
  • Understanding ERK's role requires investigating protein stability, downstream transcription factors, and chromatin modifications.
  • Further research into the intricate signaling network is essential for fully elucidating ERK-mediated cell fate determination.
Keywords:
EMTERKapoptosiscell fatecell proliferationcell signalingpluripotencysenescence

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