Center for Life Sciences, School of Life Sciences, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming, China.
The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
Cell Commun Signal. 2022 Sep 1;20(1):135. doi: 10.1186/s12964-022-00920-5.
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.
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.
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..
Our results indicate that NHR-14/HNF4α cooperates with CEP-1/p53 to regulate DNA damage-induced apoptosis. Video abstract.
核激素受体参与转录调控和许多重要的细胞过程，包括发育和代谢。然而，它在 DNA 损伤诱导的细胞凋亡中的作用仍不清楚。
用不同剂量的γ射线辐照同步的成年动物，然后在 20°C 下放回培养。在不同时间点对生殖细胞凋亡进行评分。
nhr-14 的缺失导致 DNA 损伤诱导的生殖细胞凋亡减少，但不影响生理程序性细胞死亡。我们还证明 nhr-14 在下一个 DNA 损伤检查点途径中起作用。此外，我们表明 nhr-14 在 DNA 损伤后调节 egl-1 和 ced-13 的转录。在机制上，NHR-14 与 CEP-1/p53 形成复合物，并直接结合到 egl-1 启动子上，促进 egl-1 的转录。
我们的结果表明，NHR-14/HNF4α 与 CEP-1/p53 合作调节 DNA 损伤诱导的细胞凋亡。视频摘要。
