• 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

致癌病毒蛋白HPV E7可上调人宫颈癌细胞中的SIRT1长寿蛋白。

Oncogenic viral protein HPV E7 up-regulates the SIRT1 longevity protein in human cervical cancer cells.

作者信息

Allison Simon J, Jiang Ming, Milner Jo

机构信息

Yorkshire Cancer Research P53 Research Unit, Department of Biology, University of York, York YO105DD, UK.

出版信息

Aging (Albany NY). 2009 Mar 2;1(3):316-27. doi: 10.18632/aging.100028.

DOI:10.18632/aging.100028
PMID:20157519
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2806013/
Abstract

Senescence is blocked in human cervical keratinocytes infected with high risk human papillomavirus (e.g. HPV type16). Viral oncoproteins HPV E6 and HPV E7 access the cell cycle via cellular p53 and retinoblastoma proteins respectively. Previously we have shown that HPV E7, not HPV E6, is also responsible for cervical cancer cell survival (SiHa cells; HPV type16). We now present evidence that SIRT1, an aging-related NAD-dependent deacetylase, mediates HPV E7 survival function in SiHa cervical cancer cells. Moreover, HPV E7 up-regulates SIRT1 protein when expressed in primary human keratinocytes. Conversely, SIRT1 levels decrease following RNAi-mediated silencing of HPV E7 in SiHa cells. Silencing HPV E6 has no effect on SIRT1 but, as expected, causes marked accumulation of p53 protein accompanied by p53-mediated up-regulation of p21. However, p53 acetylation (K382Ac) was barely detectable. Since p53 is a known SIRT1 substrate we propose that elevated SIRT1 levels (induced by HPV E7) attenuate p53 pro-apoptotic capacity via its de-acetylation. Our discovery that HPV E7 up-regulates SIRT1 links a clinically important oncogenic virus with the multi-functional SIRT1 protein. This link may open the way for a more in-depth understanding of the process of HPV-induced malignant transformation and also of the inter-relationships between aging and cancer.

摘要

在感染高危型人乳头瘤病毒（如16型人乳头瘤病毒）的人宫颈角质形成细胞中，衰老被阻断。病毒癌蛋白HPV E6和HPV E7分别通过细胞p53蛋白和视网膜母细胞瘤蛋白进入细胞周期。此前我们已经表明，是HPV E7而非HPV E6，也对宫颈癌细胞（SiHa细胞；16型人乳头瘤病毒）的存活负责。我们现在提供证据表明，SIRT1，一种与衰老相关的NAD依赖性脱乙酰酶，在SiHa宫颈癌细胞中介导HPV E7的存活功能。此外，HPV E7在原代人角质形成细胞中表达时会上调SIRT1蛋白。相反，在SiHa细胞中，RNAi介导的HPV E7沉默后，SIRT1水平降低。沉默HPV E6对SIRT1没有影响，但正如预期的那样，会导致p53蛋白明显积累，并伴随p53介导的p21上调。然而，几乎检测不到p53乙酰化（K382Ac）。由于p53是已知的SIRT1底物，我们提出升高的SIRT1水平（由HPV E7诱导）通过其去乙酰化减弱p53的促凋亡能力。我们发现HPV E7上调SIRT1，将一种临床上重要的致癌病毒与多功能SIRT1蛋白联系起来。这种联系可能为更深入了解HPV诱导的恶性转化过程以及衰老与癌症之间的相互关系开辟道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d663/2806013/dbed41b3224a/aging-01-316-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d663/2806013/bcd509ed0787/aging-01-316-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d663/2806013/bafe73002b58/aging-01-316-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d663/2806013/8a14b36b432d/aging-01-316-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d663/2806013/da7f424605b4/aging-01-316-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d663/2806013/dbed41b3224a/aging-01-316-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d663/2806013/bcd509ed0787/aging-01-316-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d663/2806013/bafe73002b58/aging-01-316-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d663/2806013/8a14b36b432d/aging-01-316-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d663/2806013/da7f424605b4/aging-01-316-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d663/2806013/dbed41b3224a/aging-01-316-g005.jpg

相似文献

1
Oncogenic viral protein HPV E7 up-regulates the SIRT1 longevity protein in human cervical cancer cells.致癌病毒蛋白HPV E7可上调人宫颈癌细胞中的SIRT1长寿蛋白。
Aging (Albany NY). 2009 Mar 2;1(3):316-27. doi: 10.18632/aging.100028.
2
RNA interference against HPV16 E7 oncogene leads to viral E6 and E7 suppression in cervical cancer cells and apoptosis via upregulation of Rb and p53.针对人乳头瘤病毒16型E7癌基因的RNA干扰通过上调Rb和p53导致宫颈癌细胞中的病毒E6和E7受到抑制并引发细胞凋亡。
Apoptosis. 2008 Feb;13(2):273-81. doi: 10.1007/s10495-007-0163-8.
3
In vitro and in vivo growth inhibition of human cervical cancer cells via human papillomavirus E6/E7 mRNAs' cleavage by CRISPR/Cas13a system.通过 CRISPR/Cas13a 系统切割人乳头瘤病毒 E6/E7 mRNA 抑制人宫颈癌细胞的体外和体内生长。
Antiviral Res. 2020 Jun;178:104794. doi: 10.1016/j.antiviral.2020.104794. Epub 2020 Apr 14.
4
Silencing E6/E7 Oncoproteins in SiHa Cells Treated with siRNAs and Oroxylum indicum Extracts Induced Apoptosis by Upregulating p53/pRb Pathways.用 siRNA 和醉鱼草提取物处理 SiHa 细胞，沉默 E6/E7 癌蛋白，通过上调 p53/pRb 通路诱导细胞凋亡。
Appl Biochem Biotechnol. 2024 Jul;196(7):4234-4255. doi: 10.1007/s12010-023-04762-w. Epub 2023 Nov 3.
5
Antisense targeting human papillomavirus type 16 E6 and E7 genes contributes to apoptosis and senescence in SiHa cervical carcinoma cells.反义靶向人乳头瘤病毒16型E6和E7基因可促进SiHa宫颈癌细胞的凋亡和衰老。
Gynecol Oncol. 2007 Aug;106(2):299-304. doi: 10.1016/j.ygyno.2007.04.039. Epub 2007 Jun 21.
6
Withaferin A induces p53-dependent apoptosis by repression of HPV oncogenes and upregulation of tumor suppressor proteins in human cervical cancer cells.铁皮石斛酚通过抑制 HPV 癌基因和上调肿瘤抑制蛋白诱导人宫颈癌 p53 依赖性凋亡。
Carcinogenesis. 2011 Nov;32(11):1697-705. doi: 10.1093/carcin/bgr192. Epub 2011 Aug 22.
7
Effects of HPV-16 E5, E6 and E7 proteins on survival, adhesion, migration and invasion of trophoblastic cells.HPV-16 E5、E6 和 E7 蛋白对滋养层细胞存活、黏附、迁移和侵袭的影响。
Carcinogenesis. 2010 Mar;31(3):473-80. doi: 10.1093/carcin/bgp281. Epub 2009 Nov 16.
8
E6/E7 and E6 From HPV16 and HPV18 Upregulate IL-6 Expression Independently of p53 in Keratinocytes.E6/E7 和 HPV16、HPV18 的 E6 上调角质形成细胞中的 IL-6 表达，与 p53 无关。
Front Immunol. 2019 Jul 23;10:1676. doi: 10.3389/fimmu.2019.01676. eCollection 2019.
9
Alpha-linolenic acid regulates Cox2/VEGF/MAP kinase pathway and decreases the expression of HPV oncoproteins E6/E7 through restoration of p53 and Rb expression in human cervical cancer cell lines.α-亚麻酸通过恢复人宫颈癌细胞系中p53和Rb的表达来调节Cox2/VEGF/丝裂原活化蛋白激酶途径，并降低人乳头瘤病毒癌蛋白E6/E7的表达。
Tumour Biol. 2016 Mar;37(3):3295-305. doi: 10.1007/s13277-015-4170-z. Epub 2015 Oct 6.
10
Repression of human papillomavirus oncogenes in HeLa cervical carcinoma cells causes the orderly reactivation of dormant tumor suppressor pathways.人乳头瘤病毒致癌基因在HeLa宫颈癌细胞中的抑制会导致休眠的肿瘤抑制途径有序重新激活。
Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12513-8. doi: 10.1073/pnas.97.23.12513.

引用本文的文献

1
Acetylation in Viral Infection and Disease.病毒感染与疾病中的乙酰化作用
Results Probl Cell Differ. 2025;75:329-361. doi: 10.1007/978-3-031-91459-1_12.
2
Immunoexpression of SIRT1, 6, and 7 in oral leukoplakia and oral squamous cell carcinoma.SIRT1、6、7 在口腔白斑病和口腔鳞状细胞癌中的免疫表达。
Odontology. 2024 Jan;112(1):221-229. doi: 10.1007/s10266-023-00816-x. Epub 2023 May 16.
3
High Risk-Human Papillomavirus in HNSCC: Present and Future Challenges for Epigenetic Therapies.头颈部鳞状细胞癌中高危型人乳头瘤病毒：表观遗传学治疗的当前和未来挑战。

本文引用的文献

1
Cellular regulation of SIRT1.SIRT1的细胞调节
Curr Pharm Des. 2009;15(1):39-44. doi: 10.2174/138161209787185841.
2
How does SIRT1 affect metabolism, senescence and cancer?沉默调节蛋白1如何影响新陈代谢、衰老和癌症？
Nat Rev Cancer. 2009 Feb;9(2):123-8. doi: 10.1038/nrc2562. Epub 2008 Dec 29.
3
The common mechanisms of transformation by the small DNA tumor viruses: The inactivation of tumor suppressor gene products: p53.小型DNA肿瘤病毒导致细胞转化的常见机制：肿瘤抑制基因产物的失活：p53。
Int J Mol Sci. 2022 Mar 23;23(7):3483. doi: 10.3390/ijms23073483.
4
Regulation of the Human Papillomavirus Lifecyle through Post-Translational Modifications of the Viral E2 Protein.通过病毒E2蛋白的翻译后修饰对人乳头瘤病毒生命周期的调控
Pathogens. 2021 Jun 23;10(7):793. doi: 10.3390/pathogens10070793.
5
Persistent Human Papillomavirus Infection.持续性人乳头瘤病毒感染。
Viruses. 2021 Feb 20;13(2):321. doi: 10.3390/v13020321.
6
SIRT1 and gynecological malignancies (Review).SIRT1 与妇科恶性肿瘤（综述）。
Oncol Rep. 2021 Apr;45(4). doi: 10.3892/or.2021.7994. Epub 2021 Mar 2.
7
Epigenetic Regulation of the Human Papillomavirus Life Cycle.人乳头瘤病毒生命周期的表观遗传调控
Pathogens. 2020 Jun 18;9(6):483. doi: 10.3390/pathogens9060483.
8
Upregulation of SIRT1 gene in gastric adenocarcinoma.胃腺癌中SIRT1基因的上调
Turk J Gastroenterol. 2019 Apr;30(4):326-330. doi: 10.5152/tjg.2019.18550.
9
Regulation of Chemokines and Cytokines by Histone Deacetylases and an Update on Histone Decetylase Inhibitors in Human Diseases.组蛋白去乙酰化酶对趋化因子和细胞因子的调控及组蛋白去乙酰化酶抑制剂在人类疾病中的研究进展。
Int J Mol Sci. 2019 Mar 5;20(5):1110. doi: 10.3390/ijms20051110.
10
Vorinostat, a pan-HDAC inhibitor, abrogates productive HPV-18 DNA amplification.伏立诺他，一种组蛋白去乙酰化酶抑制剂，可阻断 HPV-18 病毒的有效 DNA 扩增。
Proc Natl Acad Sci U S A. 2018 Nov 20;115(47):E11138-E11147. doi: 10.1073/pnas.1801156115. Epub 2018 Nov 1.
Virology. 2009 Feb 20;384(2):285-93. doi: 10.1016/j.virol.2008.09.034. Epub 2008 Dec 11.
4
SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging.SIRT1在染色质上的重新分布促进基因组稳定性，但在衰老过程中会改变基因表达。
Cell. 2008 Nov 28;135(5):907-18. doi: 10.1016/j.cell.2008.10.025.
5
Aging: a sirtuin shake-up?衰老：是对去乙酰化酶的一次颠覆？
Cell. 2008 Nov 28;135(5):797-8. doi: 10.1016/j.cell.2008.11.008.
6
Interplay among BRCA1, SIRT1, and Survivin during BRCA1-associated tumorigenesis.BRCA1相关肿瘤发生过程中BRCA1、SIRT1和Survivin之间的相互作用。
Mol Cell. 2008 Oct 10;32(1):11-20. doi: 10.1016/j.molcel.2008.09.011.
7
JNK2-dependent regulation of SIRT1 protein stability.JNK2 依赖的 SIRT1 蛋白稳定性调控
Cell Cycle. 2008 Oct;7(19):3091-7. doi: 10.4161/cc.7.19.6799. Epub 2008 Oct 15.
8
Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice.SIRT1 突变小鼠的 DNA 损伤反应受损、基因组不稳定与肿瘤发生
Cancer Cell. 2008 Oct 7;14(4):312-23. doi: 10.1016/j.ccr.2008.09.001.
9
The ups and downs of SIRT1.SIRT1的兴衰
Trends Biochem Sci. 2008 Nov;33(11):517-25. doi: 10.1016/j.tibs.2008.08.001. Epub 2008 Sep 18.
10
miR-34a repression of SIRT1 regulates apoptosis.miR-34a对SIRT1的抑制作用调控细胞凋亡。
Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13421-6. doi: 10.1073/pnas.0801613105. Epub 2008 Aug 28.