• 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

p53 依赖性衰老延迟 Emu-myc 诱导的 B 细胞淋巴瘤发生。

p53-dependent senescence delays Emu-myc-induced B-cell lymphomagenesis.

机构信息

Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

出版信息

Oncogene. 2010 Mar 4;29(9):1260-9. doi: 10.1038/onc.2009.423. Epub 2009 Nov 23.

DOI:10.1038/onc.2009.423
PMID:19935700
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2903442/
Abstract

The effect of p53-dependent cell-cycle arrest and senescence on Emu-myc-induced B-cell lymphoma development remains controversial. To address this question, we crossed Emu-myc mice with the p53(515C) mutant mouse, encoding the mutant p53R172P protein that retains the ability to activate the cell-cycle inhibitor and senescence activator p21. Importantly, this mutant lacks the ability to activate p53-dependent apoptotic genes. Hence, Emu-myc mice that harbor two p53(515C) alleles are completely defective for p53-dependent apoptosis. Both Emu-myc::p53(515C/515C) and Emu-myc::p53(515C/+) mice survive significantly longer than Emu-myc::p53(+/-) mice, indicating the importance of the p53-dependent non-apoptotic pathways in B-cell lymphomagenesis. In addition, the p53(515C) allele is deleted in several Emu-myc::p53(515C/+) lymphomas, further emphasizing the functionality of p53R172P in tumor inhibition. Lymphomas from both Emu-myc::p53(515C/515C) and Emu-myc::p53(515C/+) mice retain the ability to upregulate p21, resulting in cellular senescence. Senescence-associated beta-galactosidase (SA beta-gal) activity was observed in lymphomas from Emu-myc::p53(+/+), Emu-myc::p53(515C/515C) and Emu-myc::p53(515C /+) mice but not in lymphomas isolated from Emu-myc::p53(+/-) mice. Thus, in the absence of p53-dependent apoptosis, the ability of p53R172P to induce senescence leads to a significant delay in B-cell lymphoma development.

摘要

p53 依赖性细胞周期阻滞和衰老对 Emu-myc 诱导的 B 细胞淋巴瘤发展的影响仍存在争议。为了解决这个问题，我们将 Emu-myc 小鼠与 p53(515C) 突变小鼠杂交，该突变小鼠编码突变的 p53R172P 蛋白，该蛋白保留激活细胞周期抑制剂和衰老激活剂 p21 的能力。重要的是，这种突变体缺乏激活 p53 依赖性凋亡基因的能力。因此，携带两个 p53(515C) 等位基因的 Emu-myc 小鼠完全不能进行 p53 依赖性凋亡。Emu-myc::p53(515C/515C) 和 Emu-myc::p53(515C/+) 小鼠的存活时间明显长于 Emu-myc::p53(+/-) 小鼠，表明 p53 依赖性非凋亡途径在 B 细胞淋巴瘤发生中的重要性。此外，Emu-myc::p53(515C/+) 淋巴瘤中几个 Emu-myc::p53(515C) 等位基因缺失，进一步强调了 p53R172P 在肿瘤抑制中的功能。来自 Emu-myc::p53(515C/515C) 和 Emu-myc::p53(515C/+) 小鼠的淋巴瘤仍然能够上调 p21，导致细胞衰老。衰老相关的β-半乳糖苷酶（SA β-半乳糖苷酶）活性在 Emu-myc::p53(+/+)、Emu-myc::p53(515C/515C) 和 Emu-myc::p53(515C/+) 小鼠的淋巴瘤中观察到，但在 Emu-myc::p53(+/-) 小鼠的淋巴瘤中未观察到。因此，在没有 p53 依赖性凋亡的情况下，p53R172P 诱导衰老的能力导致 B 细胞淋巴瘤发展明显延迟。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f0/2903442/24c895a14c33/nihms203630f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f0/2903442/659dbed25966/nihms203630f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f0/2903442/3e1b6db68c50/nihms203630f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f0/2903442/42cff4949dcf/nihms203630f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f0/2903442/4d6d98d5f5f7/nihms203630f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f0/2903442/b50a8bb2ab25/nihms203630f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f0/2903442/a11fda507029/nihms203630f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f0/2903442/24c895a14c33/nihms203630f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f0/2903442/659dbed25966/nihms203630f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f0/2903442/3e1b6db68c50/nihms203630f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f0/2903442/42cff4949dcf/nihms203630f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f0/2903442/4d6d98d5f5f7/nihms203630f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f0/2903442/b50a8bb2ab25/nihms203630f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f0/2903442/a11fda507029/nihms203630f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5f0/2903442/24c895a14c33/nihms203630f7.jpg

相似文献

1
p53-dependent senescence delays Emu-myc-induced B-cell lymphomagenesis.p53 依赖性衰老延迟 Emu-myc 诱导的 B 细胞淋巴瘤发生。
Oncogene. 2010 Mar 4;29(9):1260-9. doi: 10.1038/onc.2009.423. Epub 2009 Nov 23.
2
Combined loss of PUMA and p21 accelerates c-MYC-driven lymphoma development considerably less than loss of one allele of p53.PUMA和p21的联合缺失对c-MYC驱动的淋巴瘤发展的加速作用远小于p53一个等位基因的缺失。
Oncogene. 2016 Jul 21;35(29):3866-71. doi: 10.1038/onc.2015.457. Epub 2015 Dec 7.
3
p21 delays tumor onset by preservation of chromosomal stability.p21通过维持染色体稳定性来延迟肿瘤发生。
Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19842-7. doi: 10.1073/pnas.0606343104. Epub 2006 Dec 14.
4
Loss of one allele of ARF rescues Mdm2 haploinsufficiency effects on apoptosis and lymphoma development.ARF一个等位基因的缺失挽救了Mdm2单倍剂量不足对细胞凋亡和淋巴瘤发展的影响。
Oncogene. 2004 Nov 25;23(55):8931-40. doi: 10.1038/sj.onc.1208052.
5
Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis.在Myc诱导的淋巴瘤发生过程中ARF-Mdm2-p53肿瘤抑制通路的破坏。
Genes Dev. 1999 Oct 15;13(20):2658-69. doi: 10.1101/gad.13.20.2658.
6
Mutant mice lacking alternatively spliced p53 isoforms unveil as a male-specific prognostic factor in Myc-driven B-cell lymphomas.缺失选择性剪接 p53 异构体的突变型小鼠揭示了在 Myc 驱动的 B 细胞淋巴瘤中作为一个男性特异性预后因素的。
Elife. 2024 Sep 19;13:RP92774. doi: 10.7554/eLife.92774.
7
Genomic characterisation of Eμ-Myc mouse lymphomas identifies Bcor as a Myc co-operative tumour-suppressor gene.Eμ-Myc 小鼠淋巴瘤的基因组特征鉴定 Bcor 为 Myc 合作性肿瘤抑制基因。
Nat Commun. 2017 Mar 6;8:14581. doi: 10.1038/ncomms14581.
8
IL-6 promotes MYC-induced B cell lymphomagenesis independent of STAT3.IL-6 促进了 MYC 诱导的 B 细胞淋巴瘤的发生，而不依赖于 STAT3。
PLoS One. 2021 Mar 2;16(3):e0247394. doi: 10.1371/journal.pone.0247394. eCollection 2021.
9
Chromosome stability, in the absence of apoptosis, is critical for suppression of tumorigenesis in Trp53 mutant mice.在不存在细胞凋亡的情况下，染色体稳定性对于Trp53突变小鼠肿瘤发生的抑制至关重要。
Nat Genet. 2004 Jan;36(1):63-8. doi: 10.1038/ng1282. Epub 2003 Dec 21.
10
Oncogenic c-Myc-induced lymphomagenesis is inhibited non-redundantly by the p19Arf-Mdm2-p53 and RP-Mdm2-p53 pathways.致癌性c-Myc诱导的淋巴瘤发生受到p19Arf-Mdm2-p53和RP-Mdm2-p53通路的非冗余抑制。
Oncogene. 2015 Nov 12;34(46):5709-17. doi: 10.1038/onc.2015.39. Epub 2015 Mar 30.

引用本文的文献

1
Unique Transcriptional Profiles Underlie Osteosarcomagenesis Driven by Different p53 Mutants.不同 p53 突变驱动的成骨肉瘤发生的独特转录特征。
Cancer Res. 2023 Jul 14;83(14):2297-2311. doi: 10.1158/0008-5472.CAN-22-3464.
2
Lessons from Using Genetically Engineered Mouse Models of MYC-Induced Lymphoma.利用 MYC 诱导的淋巴瘤基因工程小鼠模型获得的经验教训。
Cells. 2022 Dec 22;12(1):37. doi: 10.3390/cells12010037.
3
p53 partial loss-of-function mutations sensitize to chemotherapy.p53 部分功能丧失突变使肿瘤对化疗敏感。
Oncogene. 2022 Feb;41(7):1011-1023. doi: 10.1038/s41388-021-02141-5. Epub 2021 Dec 14.
4
Methods to Study Myc-Regulated Cellular Senescence: An Update.研究 Myc 调控的细胞衰老的方法：最新进展。
Methods Mol Biol. 2021;2318:241-254. doi: 10.1007/978-1-0716-1476-1_12.
5
Deconstructing networks of p53-mediated tumor suppression in vivo.体内 p53 介导的肿瘤抑制网络的解构。
Cell Death Differ. 2018 Jan;25(1):93-103. doi: 10.1038/cdd.2017.171. Epub 2017 Nov 3.
6
Mnt modulates Myc-driven lymphomagenesis.Mnt 调节 Myc 驱动的淋巴瘤发生。
Cell Death Differ. 2017 Dec;24(12):2117-2126. doi: 10.1038/cdd.2017.131. Epub 2017 Aug 11.
7
Regulation of the Mdm2-p53 signaling axis in the DNA damage response and tumorigenesis.DNA损伤反应和肿瘤发生过程中Mdm2-p53信号轴的调控
Transl Cancer Res. 2016 Dec;5(6):707-724. doi: 10.21037/tcr.2016.11.75.
8
Phosphorylation of the Mdm2 oncoprotein by the c-Abl tyrosine kinase regulates p53 tumor suppression and the radiosensitivity of mice.c-Abl酪氨酸激酶对Mdm2癌蛋白的磷酸化作用可调节p53的肿瘤抑制功能以及小鼠的放射敏感性。
Proc Natl Acad Sci U S A. 2016 Dec 27;113(52):15024-15029. doi: 10.1073/pnas.1611798114. Epub 2016 Dec 12.
9
The Regulation of Cellular Functions by the p53 Protein: Cellular Senescence.p53蛋白对细胞功能的调控：细胞衰老
Cold Spring Harb Perspect Med. 2017 Feb 1;7(2):a026112. doi: 10.1101/cshperspect.a026112.
10
Multi-focal control of mitochondrial gene expression by oncogenic MYC provides potential therapeutic targets in cancer.致癌性MYC对线粒体基因表达的多焦点控制为癌症提供了潜在的治疗靶点。
Oncotarget. 2016 Nov 8;7(45):72395-72414. doi: 10.18632/oncotarget.11718.

本文引用的文献

1
The inherent instability of mutant p53 is alleviated by Mdm2 or p16INK4a loss.Mdm2缺失或p16INK4a缺失可缓解突变型p53的固有不稳定性。
Genes Dev. 2008 May 15;22(10):1337-44. doi: 10.1101/gad.1662908.
2
Short telomeres limit tumor progression in vivo by inducing senescence.短端粒通过诱导衰老来限制体内肿瘤进展。
Cancer Cell. 2007 May;11(5):461-9. doi: 10.1016/j.ccr.2007.02.026. Epub 2007 Apr 12.
3
p21 delays tumor onset by preservation of chromosomal stability.p21通过维持染色体稳定性来延迟肿瘤发生。
Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19842-7. doi: 10.1073/pnas.0606343104. Epub 2006 Dec 14.
4
p53-Dependent and -independent functions of the Arf tumor suppressor.抑癌蛋白Arf的p53依赖性和非依赖性功能
Cold Spring Harb Symp Quant Biol. 2005;70:129-37. doi: 10.1101/sqb.2005.70.004.
5
Chromosome stability, in the absence of apoptosis, is critical for suppression of tumorigenesis in Trp53 mutant mice.在不存在细胞凋亡的情况下，染色体稳定性对于Trp53突变小鼠肿瘤发生的抑制至关重要。
Nat Genet. 2004 Jan;36(1):63-8. doi: 10.1038/ng1282. Epub 2003 Dec 21.
6
Loss of p27(Kip1) but not p21(Cip1) decreases survival and synergizes with MYC in murine lymphomagenesis.p27（Kip1）缺失而非p21（Cip1）缺失会降低生存率，并在小鼠淋巴瘤发生过程中与MYC协同作用。
EMBO J. 2002 Jul 15;21(14):3739-48. doi: 10.1093/emboj/cdf364.
7
Dissecting p53 tumor suppressor functions in vivo.在体内剖析p53肿瘤抑制功能。
Cancer Cell. 2002 Apr;1(3):289-98. doi: 10.1016/s1535-6108(02)00047-8.
8
A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy.由p53和p16INK4a控制的衰老程序对癌症治疗的结果有影响。
Cell. 2002 May 3;109(3):335-46. doi: 10.1016/s0092-8674(02)00734-1.
9
Bax loss impairs Myc-induced apoptosis and circumvents the selection of p53 mutations during Myc-mediated lymphomagenesis.Bax缺失会损害Myc诱导的细胞凋亡，并在Myc介导的淋巴瘤发生过程中规避p53突变的选择。
Mol Cell Biol. 2001 Nov;21(22):7653-62. doi: 10.1128/MCB.21.22.7653-7662.2001.
10
Surfing the p53 network.探索p53网络
Nature. 2000 Nov 16;408(6810):307-10. doi: 10.1038/35042675.