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Updated: Aug 30, 2025

Modeling Age-Associated Neurodegenerative Diseases in Caenorhabditis elegans
Published on: August 15, 2020
Caenorhabditis elegans NHR-14/HNF4α regulates DNA damage-induced apoptosis through cooperating with cep-1/p53
Lei Sang1, Rui Dong1, Rui Liu2
1Center for Life Sciences, School of Life Sciences, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming, China.
Background:
Nuclear hormone receptors are involved in transcriptional regulation and many important cellular processes including development and metabolism. However, its role in DNA damage-induced apoptosis remains elusive.
Methods:
Synchronized young adult animals were irradiated with different doses of gamma-Ray, and then put back to culture at 20 °C. Germline cell apoptosis was scored at different time point.
Results:
Deletion of nhr-14 led to decreased DNA damage-induced germline apoptosis, but not the physiological programmed cell death. We also demonstrate that nhr-14 functions downstream of the DNA damage checkpoint pathway. Moreover, we show that nhr-14 regulates egl-1 and ced-13 transcription upon DNA damage. Mechanistically, NHR-14 forms a complex with CEP-1/p53 and binds directly to the egl-1 promoter to promote egl-1 transcription..
Conclusions:
Our results indicate that NHR-14/HNF4α cooperates with CEP-1/p53 to regulate DNA damage-induced apoptosis. Video abstract.
Insights
Nuclear hormone receptor NHR-14 is crucial for DNA damage-induced apoptosis by partnering with CEP-1/p53 to regulate gene transcription. This finding clarifies the role of nuclear hormone receptors in cellular stress responses.
Area of Science:
- Molecular Biology
- Cellular Biology
- Genetics
Background:
- Nuclear hormone receptors regulate key cellular processes like development and metabolism.
- The specific role of nuclear hormone receptors in DNA damage-induced apoptosis was previously unclear.
Purpose of the Study:
- To investigate the role of nuclear hormone receptors in DNA damage-induced apoptosis.
- To elucidate the molecular mechanisms underlying this process.
Main Methods:
- Irradiation of young adult animals with varying doses of gamma-ray.
- Culturing irradiated animals at 20°C and scoring germline cell apoptosis at different time points.
Main Results:
- Deletion of nhr-14 significantly reduced DNA damage-induced germline apoptosis, but not physiological programmed cell death.
- NHR-14 functions downstream of the DNA damage checkpoint pathway.
- NHR-14 directly binds to the egl-1 promoter, forming a complex with CEP-1/p53 to promote egl-1 transcription.
Conclusions:
- NHR-14 cooperates with CEP-1/p53 to regulate DNA damage-induced apoptosis.
- This study identifies a novel role for NHR-14 in the cellular response to DNA damage.
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The Extrinsic Apoptotic Pathway

