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Caenorhabditis elegans NHR-14/HNF4α regulates DNA damage-induced apoptosis through cooperating with cep-1/p53

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 dos...

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Detalles Bibliográficos
Autores principales: Sang, Lei, Dong, Rui, Liu, Rui, Hao, Qinggang, Bai, Weiyu, Sun, Jianwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9438139/
https://www.ncbi.nlm.nih.gov/pubmed/36050770
http://dx.doi.org/10.1186/s12964-022-00920-5
Descripción
Sumario: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. GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-022-00920-5.