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Endoplasmic reticulum stress stimulates p53 expression through NF-κB activation
Wan-Chi Lin1, Yu-Chi Chuang, Yung-Sheng Chang
1Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
Plos One
|August 4, 2012
Summary
Endoplasmic reticulum (ER) stress induces apoptosis via NF-κB signaling pathways, increasing p53 expression. This pathway is crucial for cancer chemotherapy efficacy, highlighting its role in ER stress-induced cell death.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Endoplasmic reticulum (ER) stress is a key factor in disease development and a target for cancer chemotherapy.
- While p53 is known to regulate ER stress-induced apoptosis, its upstream regulators remain unclear.
Purpose of the Study:
- To elucidate the regulatory mechanisms of p53 expression during ER stress.
- To investigate the role of NF-κB signaling in ER stress-induced apoptosis.
Main Methods:
- Utilized MCF-7 and Hela cells treated with ER stress inducers (Tunicamycin, Brefeldin A).
- Assessed p53 and NF-κB (p65) expression, nuclear localization, activity, and phosphorylation.
- Employed NF-κB inhibitor (Bay 11-7082) and p53 siRNA to study pathway inhibition.
Main Results:
- ER stress inducers increased p53 expression, nuclear localization, and phosphorylation at serine 15.
- NF-κB signaling pathway activation and nuclear translocation were observed during ER stress.
- Inhibition of NF-κB or p53 significantly reduced ER stress-induced apoptosis.
Conclusions:
- NF-κB activation and subsequent p53 induction are essential for ER stress-induced cell death.
- This pathway is critical for the therapeutic efficacy of cancer drugs that induce ER stress.
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