MDM2 促进 SUMO-2/3 对 p53 的修饰，从而调节转录活性。
MDM2 promotes SUMO-2/3 modification of p53 to modulate transcriptional activity.
机构信息
The Beatson Institute for Cancer Research; Glasgow, UK.
出版信息
Cell Cycle. 2011 Sep 15;10(18):3176-88. doi: 10.4161/cc.10.18.17436.
Abstract
The tumor suppressor p53 is extensively regulated by post-translational modification, including modification by the small ubiquitin-related modifier SUMO. We show here that MDM2, previously shown to promote ubiquitin, Nedd8 and SUMO-1 modification of p53, can also enhance conjugation of endogenous SUMO-2/3 to p53. Sumoylation activity requires p53-MDM2 binding but does not depend on an intact RING finger. Both ARF and L11 can promote SUMO-2/3 conjugation of p53. However, unlike the previously described SUMO-1 conjugation of p53 by an MDM2-ARF complex, this activity does not depend on the ability of MDM2 to relocalize to the nucleolus. Interestingly, the SUMO consensus is not conserved in mouse p53, which is therefore not modified by SUMO-2/3. Finally, we show that conjugation of SUMO-2/3 to p53 correlates with a reduction of both activation and repression of a subset of p53-target genes.
摘要
肿瘤抑制因子 p53 广泛受到翻译后修饰的调控，包括被小泛素相关修饰物 SUMO 修饰。我们在此表明，先前显示能促进 p53 的泛素化、Nedd8 化和 SUMO-1 化的 MDM2，还能增强内源性 SUMO-2/3 与 p53 的连接。Sumoylation 活性需要 p53-MDM2 结合，但不依赖于完整的 RING 指。ARF 和 L11 都能促进 p53 的 SUMO-2/3 连接。然而，与先前描述的由 MDM2-ARF 复合物介导的 p53 的 SUMO-1 连接不同，这种活性不依赖于 MDM2 重新定位到核仁的能力。有趣的是，SUMO 共有序列在小鼠 p53 中并不保守，因此它不被 SUMO-2/3 修饰。最后，我们表明 SUMO-2/3 与 p53 的连接与一组 p53 靶基因的激活和抑制的减少相关。
相似文献
1
MDM2 promotes SUMO-2/3 modification of p53 to modulate transcriptional activity.MDM2 促进 SUMO-2/3 对 p53 的修饰，从而调节转录活性。
Cell Cycle. 2011 Sep 15;10(18):3176-88. doi: 10.4161/cc.10.18.17436.
2
Sumoylation induced by the Arf tumor suppressor: a p53-independent function.由Arf肿瘤抑制因子诱导的类泛素化修饰：一种不依赖p53的功能
Proc Natl Acad Sci U S A. 2005 May 24;102(21):7689-94. doi: 10.1073/pnas.0502978102. Epub 2005 May 16.
3
Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a SUMO E3 ligase that is SIM-dependent and SUMO-2/3-specific.卡波氏肉瘤相关疱疹病毒 (KSHV) 编码一种 SUMO E3 连接酶，该酶依赖 SIM 并具有 SUMO-2/3 特异性。
J Biol Chem. 2010 Feb 19;285(8):5266-73. doi: 10.1074/jbc.M109.088088. Epub 2009 Dec 24.
4
Identification of a new small ubiquitin-like modifier (SUMO)-interacting motif in the E3 ligase PIASy.在E3连接酶PIASy中鉴定一种新的小泛素样修饰物（SUMO）相互作用基序。
J Biol Chem. 2017 Jun 16;292(24):10230-10238. doi: 10.1074/jbc.M117.789982. Epub 2017 Apr 28.
5
SUMO-1 modification of Mdm2 prevents its self-ubiquitination and increases Mdm2 ability to ubiquitinate p53.Mdm2的SUMO-1修饰可阻止其自身泛素化，并增强Mdm2使p53泛素化的能力。
Cell. 2000 Jun 23;101(7):753-62. doi: 10.1016/s0092-8674(00)80887-9.
6
MDM2-ARF complex regulates p53 sumoylation.MDM2-ARF复合物调节p53的SUMO化修饰。
Oncogene. 2003 Aug 14;22(34):5348-57. doi: 10.1038/sj.onc.1206851.
7
Using Biotinylated SUMO-Traps to Analyze SUMOylated Proteins.使用生物素化的SUMO捕获剂分析SUMO化蛋白。
Methods Mol Biol. 2016;1475:109-21. doi: 10.1007/978-1-4939-6358-4_8.
8
SUMO-1 modification activates the transcriptional response of p53.小泛素样修饰蛋白1（SUMO-1）修饰激活p53的转录反应。
EMBO J. 1999 Nov 15;18(22):6455-61. doi: 10.1093/emboj/18.22.6455.
9
Regulation of the p53 pathway by ubiquitin and related proteins.泛素及相关蛋白对 p53 通路的调控。
Int J Biochem Cell Biol. 2010 Oct;42(10):1618-21. doi: 10.1016/j.biocel.2010.06.011. Epub 2010 Jun 17.
10
Activation of p53 by conjugation to the ubiquitin-like protein SUMO-1.通过与类泛素蛋白SUMO-1结合激活p53。
EMBO J. 1999 Nov 15;18(22):6462-71. doi: 10.1093/emboj/18.22.6462.
引用本文的文献
1
SUMO-activating enzyme subunit 1 (SAE1) promotes non-small cell lung cancer metastasis by promoting the epithelial-mesenchymal transition through the SUMOylation of N-cadherin.小泛素样修饰激活酶亚基1（SAE1）通过N-钙黏蛋白的小泛素样修饰促进上皮-间质转化，从而促进非小细胞肺癌转移。
Sci China Life Sci. 2025 Jul 8. doi: 10.1007/s11427-023-2662-y.
2
TP53 mutations in cancer: Molecular features and therapeutic opportunities (Review).TP53 基因突变与癌症：分子特征与治疗机会（综述）。
Int J Mol Med. 2025 Jan;55(1). doi: 10.3892/ijmm.2024.5448. Epub 2024 Oct 25.
3
MDM2 provides TOP2 poison resistance by promoting proteolysis of TOP2βcc in a p53-independent manner.MDM2 通过以一种不依赖 p53 的方式促进 TOP2βcc 的蛋白水解来提供 TOP2 毒素抗性。
Cell Death Dis. 2024 Jan 23;15(1):83. doi: 10.1038/s41419-024-06474-3.
4
Expanding Roles of the E2F-RB-p53 Pathway in Tumor Suppression.E2F-RB-p53通路在肿瘤抑制中的作用扩展
Biology (Basel). 2023 Dec 11;12(12):1511. doi: 10.3390/biology12121511.
5
The Role of p53 in Nanoparticle-Based Therapy for Cancer.p53 在基于纳米颗粒的癌症治疗中的作用。
Cells. 2023 Dec 8;12(24):2803. doi: 10.3390/cells12242803.
6
The SUMOylation and ubiquitination crosstalk in cancer.癌症中的类泛素化修饰与泛素化修饰之间的相互作用
J Cancer Res Clin Oncol. 2023 Nov;149(17):16123-16146. doi: 10.1007/s00432-023-05310-z. Epub 2023 Aug 28.
7
Role of SUMOylation in Neurodegenerative Diseases.SUMOylation 在神经退行性疾病中的作用。
Cells. 2022 Oct 27;11(21):3395. doi: 10.3390/cells11213395.
8
Cancer-Associated Dysregulation of Sumo Regulators: Proteases and Ligases.癌症相关的 SUMO 调节因子失调：蛋白酶和连接酶。
Int J Mol Sci. 2022 Jul 20;23(14):8012. doi: 10.3390/ijms23148012.
9
SUMOylation and NEDDylation in Primary and Metastatic Cancers to Bone.原发性和转移性骨癌中的小泛素样修饰和类泛素化修饰
Front Cell Dev Biol. 2022 Apr 6;10:889002. doi: 10.3389/fcell.2022.889002. eCollection 2022.
10
The Role of SUMO E3 Ligases in Signaling Pathway of Cancer Cells.SUMO E3连接酶在癌细胞信号通路中的作用
Int J Mol Sci. 2022 Mar 26;23(7):3639. doi: 10.3390/ijms23073639.
本文引用的文献
1
PKCζ mediates disturbed flow-induced endothelial apoptosis via p53 SUMOylation.PKCζ 通过 p53 SUMOylation 介导紊乱血流诱导的内皮细胞凋亡。
J Cell Biol. 2011 May 30;193(5):867-84. doi: 10.1083/jcb.201010051.
2
One function--multiple mechanisms: the manifold activities of p53 as a transcriptional repressor.一种功能——多种机制：p53作为转录抑制因子的多种活性
J Biomed Biotechnol. 2011;2011:464916. doi: 10.1155/2011/464916. Epub 2011 Mar 8.
3
The nucleolar SUMO-specific protease SMT3IP1/SENP3 attenuates Mdm2-mediated p53 ubiquitination and degradation.核仁 SUMO 特异性蛋白酶 SMT3IP1/SENP3 减弱 Mdm2 介导的 p53 泛素化和降解。
Biochem Biophys Res Commun. 2011 Mar 11;406(2):285-91. doi: 10.1016/j.bbrc.2011.02.034. Epub 2011 Feb 18.
4
SUMO E3 ligase activity of TRIM proteins.TRIM 蛋白的 SUMO E3 连接酶活性。
Oncogene. 2011 Mar 3;30(9):1108-16. doi: 10.1038/onc.2010.462. Epub 2010 Oct 25.
5
Adenovirus E1B 55-kilodalton protein is a p53-SUMO1 E3 ligase that represses p53 and stimulates its nuclear export through interactions with promyelocytic leukemia nuclear bodies.腺病毒 E1B 55 千道尔顿蛋白是一种 p53-SUMO1 E3 连接酶，通过与早幼粒细胞白血病核体的相互作用，抑制 p53 并刺激其核输出。
J Virol. 2010 Dec;84(23):12210-25. doi: 10.1128/JVI.01442-10. Epub 2010 Sep 22.
6
Nucleostemin: Another nucleolar "Twister" of the p53-MDM2 loop.核干细胞蛋白：p53-MDM2 环中的另一个核仁“扭结”。
Cell Cycle. 2010 Aug 15;9(16):3227-32. doi: 10.4161/cc.9.16.12605. Epub 2010 Aug 4.
7
Mechanisms, regulation and consequences of protein SUMOylation.蛋白质SUMO化修饰的机制、调控及后果
Biochem J. 2010 May 13;428(2):133-45. doi: 10.1042/BJ20100158.
8
Functional mimicry of the acetylated C-terminal tail of p53 by a SUMO-1 acetylated domain, SAD.SUMO-1 乙酰化结构域 SAD 通过功能模拟 p53 的乙酰化 C 末端尾巴。
J Cell Physiol. 2010 Nov;225(2):371-84. doi: 10.1002/jcp.22224.
9
Reduced transcriptional activity in the p53 pathway of senescent cells revealed by the MDM2 antagonist nutlin-3.MDM2拮抗剂Nutlin-3揭示衰老细胞p53途径中转录活性降低。
Aging (Albany NY). 2009 Sep 25;1(10):845-54. doi: 10.18632/aging.100091.
10
NUB1 promotes cytoplasmic localization of p53 through cooperation of the NEDD8 and ubiquitin pathways.NUB1 通过 NEDD8 和泛素途径的合作促进 p53 的细胞质定位。
Oncogene. 2010 Apr 15;29(15):2252-61. doi: 10.1038/onc.2009.494. Epub 2010 Jan 25.
Zotero 插件