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FOXO1介导的STAT3和AKT1核隔离触发缺氧颗粒细胞中FOXO3依赖的自噬性死亡。

FOXO1-mediated nuclear sequestration of STAT3 and AKT1 triggers FOXO3-dependent autophagic death in hypoxic granulosa cells.

作者信息

Li Chengyu, Wu Gang, Ning Caibo, Liu Zhaojun, Tao Jingli, Lu Xiumei, Shen Ming, Liu Honglin

机构信息

College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.

出版信息

Int J Biol Sci. 2024 Nov 4;20(15):5939-5958. doi: 10.7150/ijbs.101309. eCollection 2024.

DOI:10.7150/ijbs.101309
PMID:39664580
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11628327/
Abstract

FOXO proteins, especially FOXO1 and FOXO3, are recognized for their roles in controlling apoptosis and autophagy. Both apoptosis and autophagy have been induced in granulosa cells (GCs) by hypoxic conditions in ovarian follicles; however, the exact contribution of FOXO proteins and autophagy to the regulation of GCs apoptosis under hypoxia remains unclear. In this investigation of porcine GCs, we reveal that FOXO1 promotes apoptosis in response to hypoxia through FOXO3-dependent autophagy. We describe how mechanistically, FOXO1 forms a complex with the transcription factor STAT3 during hypoxia. Guided by FOXO1, this complex undergoes nuclear translocation and effectively attaches to the STAT3-responsive element (SRE) located in the FOXO3 promoter region, thereby enhancing the transcriptional expression of FOXO3. Simultaneously, FOXO1 associates with AKT1, thus facilitating its nuclear entry and subsequently reducing the Ser253 phosphorylation of FOXO3, leading to FOXO3 detachment from 14-3-3 and promoting FOXO3 translocation into the nucleus. FOXO3 subsequently stimulates the upregulation of ATG3, ultimately initiating autophagy and autophagy-dependent apoptosis. Our results suggest that hypoxia acts through FOXO1 to induce autophagic death in porcine GCs by promoting the expression and nuclear import of FOXO3.

摘要

FOXO蛋白，尤其是FOXO1和FOXO3，因其在控制细胞凋亡和自噬中的作用而被认可。卵巢卵泡中的低氧条件已在颗粒细胞（GCs）中诱导了细胞凋亡和自噬；然而，FOXO蛋白和自噬在低氧条件下对GCs凋亡调控的确切作用仍不清楚。在这项对猪GCs的研究中，我们发现FOXO1通过依赖FOXO3的自噬促进低氧诱导的细胞凋亡。我们描述了在低氧条件下，FOXO1如何与转录因子STAT3形成复合物的机制。在FOXO1的引导下，该复合物发生核转位，并有效地附着于位于FOXO3启动子区域的STAT3反应元件（SRE），从而增强FOXO3的转录表达。同时，FOXO1与AKT1结合，从而促进其进入细胞核，随后降低FOXO3的Ser253磷酸化水平，导致FOXO3从14-3-3解离，并促进FOXO3转位进入细胞核。FOXO3随后刺激ATG3的上调，最终启动自噬和自噬依赖性细胞凋亡。我们的结果表明，低氧通过FOXO1促进FOXO3的表达和核输入，从而诱导猪GCs发生自噬性死亡。

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2
FOXO1 mediates hypoxia-induced G0/G1 arrest in ovarian somatic granulosa cells by activating the TP53INP1-p53-CDKN1A pathway.FOXO1 通过激活 TP53INP1-p53-CDKN1A 通路介导缺氧诱导的卵巢体腔颗粒细胞 G0/G1 期阻滞。
Development. 2021 Jul 15;148(14). doi: 10.1242/dev.199453.
3
Expression Regulation and Physiological Role of Transcription Factor FOXO3a During Ovarian Follicular Development.
转录因子FOXO3a在卵泡发育过程中的表达调控及生理作用
Front Physiol. 2020 Nov 5;11:595086. doi: 10.3389/fphys.2020.595086. eCollection 2020.
4
Involvement of JNK/FOXO1 pathway in apoptosis induced by severe hypoxia in porcine granulosa cells.JNK/FOXO1通路在猪颗粒细胞严重缺氧诱导的细胞凋亡中的作用
Theriogenology. 2020 Sep 15;154:120-127. doi: 10.1016/j.theriogenology.2020.05.019. Epub 2020 May 15.
5
The FoxO-Autophagy Axis in Health and Disease.FoxO-自噬轴在健康和疾病中的作用。
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6
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Cell Mol Life Sci. 2019 Sep;76(17):3311-3322. doi: 10.1007/s00018-019-03122-4. Epub 2019 May 6.
7
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9
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10
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