MAGE-RING 蛋白复合物包含一组 E3 泛素连接酶。
MAGE-RING protein complexes comprise a family of E3 ubiquitin ligases.
机构信息
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9038, USA.
出版信息
Mol Cell. 2010 Sep 24;39(6):963-74. doi: 10.1016/j.molcel.2010.08.029.
Abstract
The melanoma antigen (MAGE) family consists of more than 60 genes, many of which are cancer-testis antigens that are highly expressed in cancer and play a critical role in tumorigenesis. However, the biochemical and cellular functions of this enigmatic family of proteins have remained elusive. Here, we identify really interesting new gene (RING) domain proteins as binding partners for MAGE family proteins. Multiple MAGE family proteins bind E3 RING ubiquitin ligases with specificity. The crystal structure of one of these MAGE-RING complexes, MAGE-G1-NSE1, reveals structural insights into MAGE family proteins and their interaction with E3 RING ubiquitin ligases. Biochemical and cellular assays demonstrate that MAGE proteins enhance the ubiquitin ligase activity of RING domain proteins. For example, MAGE-C2-TRIM28 is shown to target p53 for degradation in a proteasome-dependent manner, consistent with its tumorigenic functions. These findings define a biochemical and cellular function for the MAGE protein family.
摘要
黑色素瘤相关抗原（MAGE）家族由 60 多个基因组成，其中许多是癌症-睾丸抗原，在癌症中高度表达，在肿瘤发生中起关键作用。然而，这个神秘的蛋白家族的生化和细胞功能仍然难以捉摸。在这里，我们确定了真正有趣的新基因（RING）结构域蛋白作为 MAGE 家族蛋白的结合伴侣。多种 MAGE 家族蛋白特异性地与 E3 RING 泛素连接酶结合。其中一个 MAGE-RING 复合物，MAGE-G1-NSE1 的晶体结构揭示了 MAGE 家族蛋白及其与 E3 RING 泛素连接酶相互作用的结构见解。生化和细胞测定表明，MAGE 蛋白增强了 RING 结构域蛋白的泛素连接酶活性。例如，已经表明 MAGE-C2-TRIM28 通过蛋白酶体依赖性方式靶向 p53 进行降解，这与其致瘤功能一致。这些发现定义了 MAGE 蛋白家族的生化和细胞功能。
相似文献
1
MAGE-RING protein complexes comprise a family of E3 ubiquitin ligases.MAGE-RING 蛋白复合物包含一组 E3 泛素连接酶。
Mol Cell. 2010 Sep 24;39(6):963-74. doi: 10.1016/j.molcel.2010.08.029.
2
The melanoma-associated antigen 1 (MAGEA1) protein stimulates the E3 ubiquitin-ligase activity of TRIM31 within a TRIM31-MAGEA1-NSE4 complex.黑色素瘤相关抗原1（MAGEA1）蛋白在TRIM31-MAGEA1-NSE4复合物中刺激TRIM31的E3泛素连接酶活性。
Cell Cycle. 2015;14(6):920-30. doi: 10.1080/15384101.2014.1000112.
3
MAGE proteins regulate KRAB zinc finger transcription factors and KAP1 E3 ligase activity.黑色素瘤相关抗原（MAGE）蛋白调节KRAB锌指转录因子和KAP1 E3连接酶活性。
Arch Biochem Biophys. 2014 Dec 1;563:136-44. doi: 10.1016/j.abb.2014.07.026. Epub 2014 Aug 7.
4
When MAGE meets RING: insights into biological functions of MAGE proteins.当 MAGE 遇到 RING：对 MAGE 蛋白生物学功能的深入了解。
Protein Cell. 2011 Jan;2(1):7-12. doi: 10.1007/s13238-011-1002-9. Epub 2011 Feb 20.
5
A Comprehensive Guide to the MAGE Family of Ubiquitin Ligases.泛素连接酶MAGE家族综合指南
J Mol Biol. 2017 Apr 21;429(8):1114-1142. doi: 10.1016/j.jmb.2017.03.005. Epub 2017 Mar 11.
6
Identification of TRIM22 as a RING finger E3 ubiquitin ligase.鉴定TRIM22为一种环状指E3泛素连接酶。
Biochem Biophys Res Commun. 2008 Sep 26;374(3):502-6. doi: 10.1016/j.bbrc.2008.07.070. Epub 2008 Jul 24.
7
Structural basis for substrate recognition and chemical inhibition of oncogenic MAGE ubiquitin ligases.致癌 MAGE 泛素连接酶的底物识别和化学抑制的结构基础。
Nat Commun. 2020 Oct 1;11(1):4931. doi: 10.1038/s41467-020-18708-x.
8
Emerging roles of the MAGE protein family in stress response pathways.MAGE 蛋白家族在应激反应途径中的新作用。
J Biol Chem. 2020 Nov 20;295(47):16121-16155. doi: 10.1074/jbc.REV120.008029. Epub 2020 Sep 13.
9
MAGE-A Cancer/Testis Antigens Inhibit MDM2 Ubiquitylation Function and Promote Increased Levels of MDM4.黑色素瘤相关抗原A（MAGE-A）癌胚抗原抑制MDM2泛素化功能并促进MDM4水平升高。
PLoS One. 2015 May 22;10(5):e0127713. doi: 10.1371/journal.pone.0127713. eCollection 2015.
10
Necdin promotes ubiquitin-dependent degradation of PIAS1 SUMO E3 ligase.Necdin促进PIAS1 SUMO E3连接酶的泛素依赖性降解。
PLoS One. 2014 Jun 9;9(6):e99503. doi: 10.1371/journal.pone.0099503. eCollection 2014.
引用本文的文献
1
Melanoma antigens in pediatric medulloblastoma contribute to tumor heterogeneity and species-specificity of group 3 tumors.小儿髓母细胞瘤中的黑色素瘤抗原促成了3组肿瘤的肿瘤异质性和物种特异性。
Acta Neuropathol Commun. 2025 Jul 28;13(1):164. doi: 10.1186/s40478-025-02055-3.
2
Reciprocal stabilization of CtBP and TRIM28 represses autophagy to promote metastasis.CtBP与TRIM28的相互稳定作用抑制自噬以促进转移。
Nat Struct Mol Biol. 2025 May 15. doi: 10.1038/s41594-025-01554-0.
3
Unveiling MAGEA3: a novel predictive biomarker for bevacizumab resistance in colorectal cancer.揭示MAGEA3：一种用于预测结直肠癌中贝伐单抗耐药性的新型生物标志物。
Cancer Drug Resist. 2025 Apr 28;8:22. doi: 10.20517/cdr.2025.35. eCollection 2025.
4
CircTADA2A stabilizes p53 via interacting with TRIM28 and suppresses the maintenance of FLT3-ITD acute myeloid leukemia.环状TADA2A通过与TRIM28相互作用来稳定p53，并抑制FLT3-ITD急性髓系白血病的维持。
Leukemia. 2025 Apr 2. doi: 10.1038/s41375-025-02589-4.
5
Interplay Between TGFβ1 Signaling and Cancer-Testis Antigen MAGEB2: A New Thorn in Cancer's Side?转化生长因子β1（TGFβ1）信号传导与癌-睾丸抗原MAGEB2之间的相互作用：癌症的新麻烦？
Int J Mol Sci. 2025 Mar 9;26(6):2448. doi: 10.3390/ijms26062448.
6
Pathological modulation of genome maintenance by cancer/testes antigens (CTAs).癌症/睾丸抗原（CTAs）对基因组维持的病理调控
DNA Repair (Amst). 2025 Mar;147:103818. doi: 10.1016/j.dnarep.2025.103818. Epub 2025 Feb 16.
7
Exploring the role and mechanisms of MAGEA4 in tumorigenesis, regulation, and immunotherapy.探索MAGEA4在肿瘤发生、调控及免疫治疗中的作用和机制。
Mol Med. 2025 Feb 4;31(1):43. doi: 10.1186/s10020-025-01079-8.
8
Identification of new tissue markers for the monitoring and standardization of penile cancer according to the degree of differentiation.根据分化程度鉴定用于阴茎癌监测和标准化的新组织标志物。
Histol Histopathol. 2025 Jul;40(7):1013-1039. doi: 10.14670/HH-18-846. Epub 2024 Nov 7.
9
Modified Dendritic cell-based T-cell expansion protocol and single-cell multi-omics allow for the selection of the most expanded and -effective clonotype via profiling of thousands of MAGE-A3-specific T-cells.改良的树突状细胞 T 细胞扩增方案和单细胞多组学允许通过对数千个 MAGE-A3 特异性 T 细胞进行分析，选择最扩增和最有效的克隆型。
Front Immunol. 2024 Oct 10;15:1470130. doi: 10.3389/fimmu.2024.1470130. eCollection 2024.
10
ANKRD1 Promotes Breast Cancer Metastasis by Activating NF-B-MAGE-A6 Pathway.锚蛋白重复结构域1通过激活核因子-κB-黑色素瘤抗原基因A6通路促进乳腺癌转移。
Cancers (Basel). 2024 Sep 27;16(19):3306. doi: 10.3390/cancers16193306.
本文引用的文献
1
KAP1 is associated with peritoneal carcinomatosis in gastric cancer.KAP1 与胃癌腹膜转移有关。
Ann Surg Oncol. 2010 Mar;17(3):821-8. doi: 10.1245/s10434-009-0795-8. Epub 2009 Nov 7.
2
Trim24 targets endogenous p53 for degradation.Trim24将内源性p53作为降解靶点。
Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11612-6. doi: 10.1073/pnas.0813177106. Epub 2009 Jun 25.
3
The Yin and Yang of the MMS21-SMC5/6 SUMO ligase complex in homologous recombination.MMS21-SMC5/6 小泛素样修饰蛋白连接酶复合物在同源重组中的阴阳关系
DNA Repair (Amst). 2009 Apr 5;8(4):499-506. doi: 10.1016/j.dnarep.2009.01.009. Epub 2009 Feb 13.
4
The cancer vaccine roller coaster.癌症疫苗的起伏历程。
Nat Biotechnol. 2009 Feb;27(2):129-39. doi: 10.1038/nbt0209-129.
5
TRIM family proteins and their emerging roles in innate immunity.TRIM家族蛋白及其在固有免疫中的新作用。
Nat Rev Immunol. 2008 Nov;8(11):849-60. doi: 10.1038/nri2413.
6
The melanoma-associated antigen A3 mediates fibronectin-controlled cancer progression and metastasis.黑色素瘤相关抗原A3介导纤连蛋白控制的癌症进展和转移。
Cancer Res. 2008 Oct 1;68(19):8104-12. doi: 10.1158/0008-5472.CAN-08-2132.
7
Nse1 RING-like domain supports functions of the Smc5-Smc6 holocomplex in genome stability.Nse1 类泛素连接酶结构域支持 Smc5-Smc6 全复合体在基因组稳定性方面的功能。
Mol Biol Cell. 2008 Oct;19(10):4099-109. doi: 10.1091/mbc.e08-02-0226. Epub 2008 Jul 30.
8
MAGE-A, mMage-b, and MAGE-C proteins form complexes with KAP1 and suppress p53-dependent apoptosis in MAGE-positive cell lines.MAGE-A、mMage-b和MAGE-C蛋白与KAP1形成复合物，并在MAGE阳性细胞系中抑制p53依赖性凋亡。
Cancer Res. 2007 Oct 15;67(20):9954-62. doi: 10.1158/0008-5472.CAN-07-1478.
9
GSK's antigen-specific cancer immunotherapy programme: pilot results leading to Phase III clinical development.葛兰素史克公司的抗原特异性癌症免疫治疗项目：引领进入III期临床开发的试验结果。
Vaccine. 2007 Sep 27;25 Suppl 2:B61-71. doi: 10.1016/j.vaccine.2007.06.038.
10
The imprinted gene Magel2 regulates normal circadian output.印记基因Magel2调节正常的昼夜节律输出。
Nat Genet. 2007 Oct;39(10):1266-72. doi: 10.1038/ng2114. Epub 2007 Sep 23.
Zotero 插件