• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

热休克蛋白90（HSP90）调节脱氧胞苷激酶（dCK）稳定性并抑制子宫颈癌细胞中电离辐射诱导的铁死亡。

HSP90 regulates dCK stability and inhibits ionizing radiation-induced ferroptosis in cervical cancer cells.

作者信息

Wang Yue, Ji Huilin, Yang Tianpeng, Liu Yi, He Xiang, Jiang Xinyue, Lu Zipeng, Han Liu, Liu Xiaodong, Ma Shumei

机构信息

School of Public Health, Wenzhou Medical University, Wenzhou, China.

South Zhejiang Institute of Radiation Medicine and Nuclear Technology, Wenzhou, China.

出版信息

Cell Death Discov. 2025 Apr 22;11(1):191. doi: 10.1038/s41420-025-02388-x.

DOI:10.1038/s41420-025-02388-x
PMID:40263268
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12015294/
Abstract

Cervical squamous cell carcinoma (CESC) is one of the most common cancers in women, and radiotherapy has been used as a primary treatment. However, its efficacy is limited by intrinsic and acquired radiation resistance. Our previous study demonstrated that Deoxycytidine kinase (dCK) inhibits ionizing radiation (IR)-induced cell death, including apoptosis and mitotic catastrophe, and dCK is a HSP90-interacting protein by mass spectrometry and co-immunoprecipitation assay. In the present study, we found that dCK inhibited IR-induced ferroptosis by increasing the activity and stability of SLC7A11. Using the E3 ubiquitin ligase database (UbiBrowser), we predicted NEDD4L as a potential ubiquitin ligase of dCK, and WWP1/2 as potential ubiquitin ligases of NEDD4L, respectively. These predictions were subsequently verified through a ubiquitination IP assay. Our findings indicate that HSP90 regulates dCK stability by inhibiting NEDD4L through the recruitment of ubiquitin ligases WWP1/2. In summary, our study reveals the HSP90-WWP1/WWP2-NEDD4L-dCK-SLC7A11 axis as a critical regulator of IR-induced ferroptosis in HeLa cells. These findings provide valuable insights into potential strategies for the radiosensitization of cervical cancer.

摘要

宫颈鳞状细胞癌（CESC）是女性中最常见的癌症之一，放射治疗一直被用作主要治疗方法。然而，其疗效受到内在和获得性放射抗性的限制。我们之前的研究表明，脱氧胞苷激酶（dCK）抑制电离辐射（IR）诱导的细胞死亡，包括凋亡和有丝分裂灾难，并且通过质谱和免疫共沉淀分析发现dCK是一种与热休克蛋白90（HSP90）相互作用的蛋白。在本研究中，我们发现dCK通过增加溶质载体家族7成员11（SLC7A11）的活性和稳定性来抑制IR诱导的铁死亡。使用E3泛素连接酶数据库（UbiBrowser），我们分别预测NEDD4样泛素蛋白连接酶（NEDD4L）是dCK的潜在泛素连接酶，而WWP1/2是NEDD4L的潜在泛素连接酶。随后通过泛素化免疫沉淀试验验证了这些预测。我们的研究结果表明，HSP90通过募集泛素连接酶WWP1/2抑制NEDD4L来调节dCK的稳定性。总之，我们的研究揭示了HSP90-WWP1/WWP2-NEDD4L-dCK-SLC7A11轴是HeLa细胞中IR诱导的铁死亡的关键调节因子。这些发现为宫颈癌放射增敏的潜在策略提供了有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e3/12015294/0897c5d0cab0/41420_2025_2388_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e3/12015294/1d8ac252f7b0/41420_2025_2388_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e3/12015294/25d1c978e72f/41420_2025_2388_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e3/12015294/6029cfca3856/41420_2025_2388_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e3/12015294/f97422c2235b/41420_2025_2388_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e3/12015294/647c093fa7f2/41420_2025_2388_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e3/12015294/de55b4e82b24/41420_2025_2388_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e3/12015294/a4fbe8890628/41420_2025_2388_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e3/12015294/0897c5d0cab0/41420_2025_2388_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e3/12015294/1d8ac252f7b0/41420_2025_2388_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e3/12015294/25d1c978e72f/41420_2025_2388_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e3/12015294/6029cfca3856/41420_2025_2388_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e3/12015294/f97422c2235b/41420_2025_2388_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e3/12015294/647c093fa7f2/41420_2025_2388_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e3/12015294/de55b4e82b24/41420_2025_2388_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e3/12015294/a4fbe8890628/41420_2025_2388_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9e3/12015294/0897c5d0cab0/41420_2025_2388_Fig8_HTML.jpg

相似文献

1
HSP90 regulates dCK stability and inhibits ionizing radiation-induced ferroptosis in cervical cancer cells.热休克蛋白90（HSP90）调节脱氧胞苷激酶（dCK）稳定性并抑制子宫颈癌细胞中电离辐射诱导的铁死亡。
Cell Death Discov. 2025 Apr 22;11(1):191. doi: 10.1038/s41420-025-02388-x.
2
ESR1 inhibits ionizing radiation-induced ferroptosis in breast cancer cells via the NEDD4L/CD71 pathway.ESR1 通过 NEDD4L/CD71 通路抑制乳腺癌细胞电离辐射诱导的铁死亡。
Arch Biochem Biophys. 2022 Aug 15;725:109299. doi: 10.1016/j.abb.2022.109299. Epub 2022 May 22.
3
The Dual Regulation Effects of ESR1/NEDD4L on SLC7A11 in Breast Cancer Under Ionizing Radiation.电离辐射下ESR1/NEDD4L对乳腺癌中SLC7A11的双重调控作用
Front Cell Dev Biol. 2022 Feb 16;9:772380. doi: 10.3389/fcell.2021.772380. eCollection 2021.
4
The Role of Deoxycytidine Kinase (dCK) in Radiation-Induced Cell Death.脱氧胞苷激酶（dCK）在辐射诱导的细胞死亡中的作用。
Int J Mol Sci. 2016 Nov 21;17(11):1939. doi: 10.3390/ijms17111939.
5
NEDD4L affects KLF5 stability through ubiquitination to control ferroptosis and radiotherapy resistance in oesophageal squamous cell carcinoma.NEDD4L 通过泛素化影响 KLF5 的稳定性，从而控制食管鳞癌细胞中的铁死亡和放疗抵抗。
J Cell Mol Med. 2024 Sep;28(18):e70062. doi: 10.1111/jcmm.70062.
6
METTL3 regulates TFRC ubiquitination and ferroptosis through stabilizing NEDD4L mRNA to impact stroke.METTL3 通过稳定 NEDD4L mRNA 调节 TFRC 泛素化和铁死亡，从而影响中风。
Cell Biol Toxicol. 2024 Feb 2;40(1):8. doi: 10.1007/s10565-024-09844-x.
7
E2-derived peptide ligands target HECT E3-E2 binding site and block the Ub-dependent SARS-CoV-2 egression: A computational study.E2 衍生肽配体靶向 HECT E3-E2 结合位点并阻断依赖 Ub 的 SARS-CoV-2 出芽：一项计算研究。
Comput Biol Med. 2022 Jul;146:105660. doi: 10.1016/j.compbiomed.2022.105660. Epub 2022 May 22.
8
NEDD4L contributes to ferroptosis and cell growth inhibition in esophageal squamous cell carcinoma by facilitating xCT ubiquitination.NEDD4L通过促进xCT泛素化，在食管鳞状细胞癌中促成铁死亡和细胞生长抑制。
Cell Death Discov. 2024 Nov 18;10(1):473. doi: 10.1038/s41420-024-02243-5.
9
Deoxycytidine kinase participates in the regulation of radiation-induced autophagy and apoptosis in breast cancer cells.脱氧胞苷激酶参与调节乳腺癌细胞辐射诱导的自噬和凋亡。
Int J Oncol. 2018 Mar;52(3):1000-1010. doi: 10.3892/ijo.2018.4250. Epub 2018 Jan 22.
10
NEDD4L-mediated LTF protein degradation limits ferroptosis.NEDD4L 介导的 LTF 蛋白降解限制铁死亡。
Biochem Biophys Res Commun. 2020 Oct 22;531(4):581-587. doi: 10.1016/j.bbrc.2020.07.032. Epub 2020 Aug 16.

本文引用的文献

1
A novel immune-related gene signature predicts the prognosis of hepatocellular carcinoma.一种新型免疫相关基因特征可预测肝细胞癌的预后。
Front Oncol. 2022 Sep 15;12:955192. doi: 10.3389/fonc.2022.955192. eCollection 2022.
2
Targeting Ferroptosis by Ubiquitin System Enzymes: A Potential Therapeutic Strategy in Cancer.靶向泛素系统酶的铁死亡：癌症治疗的潜在策略。
Int J Biol Sci. 2022 Aug 29;18(14):5475-5488. doi: 10.7150/ijbs.73790. eCollection 2022.
3
HSP90α induces immunosuppressive myeloid cells in melanoma via TLR4 signaling.
HSP90α 通过 TLR4 信号诱导黑色素瘤中的免疫抑制性髓系细胞。
J Immunother Cancer. 2022 Sep;10(9). doi: 10.1136/jitc-2022-005551.
4
Cervical cytology: Radiation and other therapy effects.宫颈细胞学检查：放射及其他治疗的影响。
Cytojournal. 2022 Apr 30;19:32. doi: 10.25259/CMAS_03_12_2021. eCollection 2022.
5
Propofol Augments Paclitaxel-Induced Cervical Cancer Cell Ferroptosis .丙泊酚增强紫杉醇诱导的宫颈癌细胞铁死亡
Front Pharmacol. 2022 Apr 20;13:816432. doi: 10.3389/fphar.2022.816432. eCollection 2022.
6
The Dual Regulation Effects of ESR1/NEDD4L on SLC7A11 in Breast Cancer Under Ionizing Radiation.电离辐射下ESR1/NEDD4L对乳腺癌中SLC7A11的双重调控作用
Front Cell Dev Biol. 2022 Feb 16;9:772380. doi: 10.3389/fcell.2021.772380. eCollection 2021.
7
USP44 regulates irradiation-induced DNA double-strand break repair and suppresses tumorigenesis in nasopharyngeal carcinoma.USP44 调控放疗诱导的 DNA 双链断裂修复并抑制鼻咽癌的发生。
Nat Commun. 2022 Jan 25;13(1):501. doi: 10.1038/s41467-022-28158-2.
8
Cdc25A inhibits autophagy-mediated ferroptosis by upregulating ErbB2 through PKM2 dephosphorylation in cervical cancer cells.Cdc25A 通过抑制 PKM2 的磷酸化来上调 ErbB2，从而抑制宫颈癌细胞自噬性铁死亡。
Cell Death Dis. 2021 Nov 6;12(11):1055. doi: 10.1038/s41419-021-04342-y.
9
MiR-499b-5p inhibits cervical cancer cell proliferation and induces apoptosis by targeting the Notch1 signaling pathway.miR-499b-5p 通过靶向 Notch1 信号通路抑制宫颈癌细胞增殖并诱导细胞凋亡。
Eur Rev Med Pharmacol Sci. 2021 Oct;25(20):6220-6231. doi: 10.26355/eurrev_202110_26992.
10
TAS-116 (Pimitespib), an Oral HSP90 Inhibitor, in Combination with Nivolumab in Patients with Colorectal Cancer and Other Solid Tumors: An Open-Label, Dose-Finding, and Expansion Phase Ib Trial (EPOC1704).TAS-116（哌米替尼），一种口服 HSP90 抑制剂，联合纳武利尤单抗治疗结直肠癌和其他实体瘤患者：一项开放标签、剂量探索和扩展的 Ib 期试验（EPOC1704）。
Clin Cancer Res. 2021 Dec 15;27(24):6709-6715. doi: 10.1158/1078-0432.CCR-21-1929. Epub 2021 Sep 30.