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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
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.
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.
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