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The NF-κB Nucleolar Stress Response Pathway.

Hazel C Thoms1, Lesley A Stark1

  • 1The Stark Lab, Edinburgh Cancer Research Centre, Institute of Genetics and Cancer, University of Edinburgh, Crewe Rd. South, Edinburgh EH4 2XU, UK.

Biomedicines
|September 28, 2021
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Summary

The nucleolus responds to cellular stress by activating NF-κB signaling. This pathway, involving p62 and TIF-IA, regulates cell death and is targeted by aspirin in colon cancer.

Keywords:
COMMD1NF-κBNPMRRN3TIF-IAaspirincolon cancernucleolinucleolusnucleophosminp62

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • The nucleolus is vital for cellular homeostasis and stress response.
  • While p53 is a known effector of nucleolar stress, NF-κB is emerging as a key regulator.
  • Understanding NF-κB's role in nucleolar stress is crucial for cancer therapy.

Purpose of the Study:

  • To review the NF-κB nucleolar stress response pathway.
  • To elucidate the mechanisms of NF-κB activation downstream of nucleolar stress.
  • To explore therapeutic targeting of this pathway in colon cancer.

Main Methods:

  • Review of existing literature on nucleolar stress and NF-κB signaling.
  • Discussion of molecular mechanisms including RelA sequestration and TIF-IA degradation.
  • Analysis of aspirin's role in targeting the TIF-IA-NF-κB pathway.

Main Results:

  • NF-κB acts downstream of nucleolar stress to control cell growth and death.
  • Nucleolar sequestration of RelA induces apoptosis, with p62 playing a role.
  • Degradation of TIF-IA activates NF-κB signaling.

Conclusions:

  • The NF-κB pathway is a significant mediator of nucleolar stress responses.
  • Targeting TIF-IA-NF-κB signaling, as with aspirin, can induce apoptosis in colon cancer cells.