转录辅助因子 TRIM24、TRIM28 和 TRIM33 形成调节复合物，抑制小鼠肝细胞癌。
Transcription cofactors TRIM24, TRIM28, and TRIM33 associate to form regulatory complexes that suppress murine hepatocellular carcinoma.
机构信息
Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 Rue Laurent Fries, 67404 Illkirch Cédex, France.
出版信息
Proc Natl Acad Sci U S A. 2011 May 17;108(20):8212-7. doi: 10.1073/pnas.1101544108. Epub 2011 Apr 29.
Abstract
TRIM24 (TIF1α), TRIM28 (TIF1β), and TRIM33 (TIF1γ) are three related cofactors belonging to the tripartite motif superfamily that interact with distinct transcription factors. TRIM24 interacts with the liganded retinoic acid (RA) receptor to repress its transcriptional activity. Germ line inactivation of TRIM24 in mice deregulates RA-signaling in hepatocytes leading to the development of hepatocellular carcinoma (HCC). Here we show that TRIM24 can be purified as at least two macromolecular complexes comprising either TRIM33 or TRIM33 and TRIM28. Somatic hepatocyte-specific inactivation of TRIM24, TRIM28, or TRIM33 all promote HCC in a cell-autonomous manner in mice. Moreover, HCC formation upon TRIM24 inactivation is strongly potentiated by further loss of TRIM33. These results demonstrate that the TIF1-related subfamily of TRIM proteins interact both physically and functionally to modulate HCC formation in mice.
摘要
TRIM24（TIF1α）、TRIM28（TIF1β）和 TRIM33（TIF1γ）是三种属于三联基序超家族的相关辅助因子，它们与不同的转录因子相互作用。TRIM24 与配体结合的视黄酸（RA）受体相互作用，抑制其转录活性。在小鼠中，TRIM24 的种系失活导致 RA 信号在肝细胞中失调，从而导致肝细胞癌（HCC）的发生。在这里，我们表明 TRIM24 可以作为至少两种包含 TRIM33 或 TRIM33 和 TRIM28 的大分子复合物进行纯化。在小鼠中，体细胞特异性失活 TRIM24、TRIM28 或 TRIM33 均可以细胞自主的方式促进 HCC 的发生。此外，TRIM24 失活后 HCC 的形成因进一步缺失 TRIM33 而大大增强。这些结果表明，TRIM 蛋白的 TIF1 相关亚家族相互作用，无论是在物理上还是在功能上，都可以调节小鼠中 HCC 的形成。
相似文献
1
Transcription cofactors TRIM24, TRIM28, and TRIM33 associate to form regulatory complexes that suppress murine hepatocellular carcinoma.转录辅助因子 TRIM24、TRIM28 和 TRIM33 形成调节复合物，抑制小鼠肝细胞癌。
Proc Natl Acad Sci U S A. 2011 May 17;108(20):8212-7. doi: 10.1073/pnas.1101544108. Epub 2011 Apr 29.
2
The TIF1α-related TRIM cofactors couple chromatin modifications to transcriptional regulation, signaling and tumor suppression.与TIF1α相关的TRIM辅助因子将染色质修饰与转录调控、信号传导及肿瘤抑制联系起来。
Transcription. 2011 Sep-Oct;2(5):231-6. doi: 10.4161/trns.2.5.17725.
3
Trim24 and Trim33 Play a Role in Epigenetic Silencing of Retroviruses in Embryonic Stem Cells.Trim24 和 Trim33 在胚胎干细胞中逆转录病毒的表观遗传沉默中发挥作用。
Viruses. 2020 Sep 11;12(9):1015. doi: 10.3390/v12091015.
4
Trim24-repressed VL30 retrotransposons regulate gene expression by producing noncoding RNA.Trim24 抑制的 VL30 反转录转座子通过产生非编码 RNA 来调节基因表达。
Nat Struct Mol Biol. 2013 Mar;20(3):339-46. doi: 10.1038/nsmb.2496. Epub 2013 Feb 3.
5
TRIM28 protects TRIM24 from SPOP-mediated degradation and promotes prostate cancer progression.TRIM28 保护 TRIM24 免受 SPOP 介导的降解，从而促进前列腺癌的进展。
Nat Commun. 2018 Nov 27;9(1):5007. doi: 10.1038/s41467-018-07475-5.
6
Tripartite motif 24 (Trim24/Tif1α) tumor suppressor protein is a novel negative regulator of interferon (IFN)/signal transducers and activators of transcription (STAT) signaling pathway acting through retinoic acid receptor α (Rarα) inhibition.三结构域蛋白 24（Trim24/Tif1α）肿瘤抑制蛋白是干扰素（IFN）/信号转导和转录激活因子（STAT）信号通路的新型负调节剂，通过抑制视黄酸受体 α（Rarα）发挥作用。
J Biol Chem. 2011 Sep 23;286(38):33369-79. doi: 10.1074/jbc.M111.225680. Epub 2011 Jul 18.
7
Loss of Trim24 (Tif1alpha) gene function confers oncogenic activity to retinoic acid receptor alpha.Trim24（Tif1alpha）基因功能丧失赋予视黄酸受体α致癌活性。
Nat Genet. 2007 Dec;39(12):1500-6. doi: 10.1038/ng.2007.15. Epub 2007 Nov 18.
8
Trim24 (Tif1 alpha): an essential 'brake' for retinoic acid-induced transcription to prevent liver cancer.Trim24（Tif1α）：视黄酸诱导转录的关键“刹车”，可预防肝癌。
Cell Cycle. 2008 Dec;7(23):3647-52. doi: 10.4161/cc.7.23.7123. Epub 2008 Dec 5.
9
Changes in SUMO-modified proteins in Epstein-Barr virus infection identifies reciprocal regulation of TRIM24/28/33 complexes and the lytic switch BZLF1.EB 病毒感染中 SUMO 修饰蛋白的变化鉴定了 TRIM24/28/33 复合物和裂解开关 BZLF1 的相互调节。
PLoS Pathog. 2023 Jul 6;19(7):e1011477. doi: 10.1371/journal.ppat.1011477. eCollection 2023 Jul.
10
Identification of Histone Peptide Binding Specificity and Small-Molecule Ligands for the TRIM33α and TRIM33β Bromodomains.鉴定 TRIM33α 和 TRIM33β 溴结构域与组蛋白肽的结合特异性和小分子配体。
ACS Chem Biol. 2022 Oct 21;17(10):2753-2768. doi: 10.1021/acschembio.2c00266. Epub 2022 Sep 13.
引用本文的文献
1
TRIM28 is a target for paramyxovirus V proteins.TRIM28是副粘病毒V蛋白的一个靶点。
PLoS Pathog. 2025 Sep 8;21(9):e1013487. doi: 10.1371/journal.ppat.1013487. eCollection 2025 Sep.
2
Regulatory role of E3 ubiquitin ligases in multiple myeloma: from molecular mechanisms to therapeutic strategies.E3泛素连接酶在多发性骨髓瘤中的调控作用：从分子机制到治疗策略
Front Cell Dev Biol. 2025 Jul 30;13:1620097. doi: 10.3389/fcell.2025.1620097. eCollection 2025.
3
TRIM33 loss reduces androgen receptor transcriptional output and H2BK120 ubiquitination.TRIM33缺失会降低雄激素受体转录输出和H2BK120泛素化。
Commun Biol. 2025 Jul 11;8(1):1043. doi: 10.1038/s42003-025-08449-2.
4
TRIM24 directs replicative stress responses to maintain ALT telomeres via chromatin signaling.TRIM24通过染色质信号传导引导复制应激反应以维持端粒延长替代途径（ALT）的端粒。
Mol Cell. 2025 Jul 17;85(14):2636-2653.e8. doi: 10.1016/j.molcel.2025.06.009. Epub 2025 Jul 3.
5
TRIM24 regulates chromatin remodeling and calcium dynamics in cardiomyocytes.TRIM24调节心肌细胞中的染色质重塑和钙动力学。
Cell Commun Signal. 2025 Jul 1;23(1):312. doi: 10.1186/s12964-025-02323-8.
6
The USP11/TCEAL1 complex promotes transcription elongation to sustain oncogenic gene expression in neuroblastoma.USP11/TCEAL1复合物促进转录延伸以维持神经母细胞瘤中的致癌基因表达。
Genes Dev. 2025 Jun 2;39(11-12):751-769. doi: 10.1101/gad.352166.124.
7
Identification of RING E3 pseudoligases in the TRIM protein family.TRIM蛋白家族中RING E3类假连接酶的鉴定。
Nat Commun. 2025 Apr 11;16(1):3456. doi: 10.1038/s41467-025-58807-1.
8
The Immune Modulatory Role of TIF1 Proteins.TIF1 蛋白的免疫调节作用。
Adv Exp Med Biol. 2024;1466:89-99. doi: 10.1007/978-981-97-7288-9_6.
9
The tripartite motif-containing 24 is a multifunctional player in human cancer.含三联基序的蛋白24在人类癌症中发挥着多功能作用。
Cell Biosci. 2024 Aug 19;14(1):103. doi: 10.1186/s13578-024-01289-3.
10
Multi-Omics Characterization of E3 Regulatory Patterns in Different Cancer Types.多组学分析不同癌症类型中 E3 调节模式。
Int J Mol Sci. 2024 Jul 11;25(14):7639. doi: 10.3390/ijms25147639.
本文引用的文献
1
TRIM24 links a non-canonical histone signature to breast cancer.TRIM24 将一种非典型的组蛋白特征与乳腺癌联系起来。
Nature. 2010 Dec 16;468(7326):927-32. doi: 10.1038/nature09542.
2
TIF1gamma controls erythroid cell fate by regulating transcription elongation.TIF1γ 通过调控转录延伸控制红细胞命运。
Cell. 2010 Jul 9;142(1):133-43. doi: 10.1016/j.cell.2010.05.028.
3
Negative control of Smad activity by ectodermin/Tif1gamma patterns the mammalian embryo.Ectodermin/Tif1γ通过负调控 Smad 活性来调控哺乳动物胚胎的形成。
Development. 2010 Aug 1;137(15):2571-8. doi: 10.1242/dev.053801. Epub 2010 Jun 23.
4
Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET.原病毒在胚胎干细胞中的沉默需要组蛋白甲基转移酶 ESET。
Nature. 2010 Apr 8;464(7290):927-31. doi: 10.1038/nature08858. Epub 2010 Feb 17.
5
KAP1 controls endogenous retroviruses in embryonic stem cells.KAP1 控制胚胎干细胞中的内源性逆转录病毒。
Nature. 2010 Jan 14;463(7278):237-40. doi: 10.1038/nature08674.
6
Inactivation of TIF1gamma cooperates with Kras to induce cystic tumors of the pancreas.TIF1γ的失活与Kras协同作用诱导胰腺囊性肿瘤。
PLoS Genet. 2009 Jul;5(7):e1000575. doi: 10.1371/journal.pgen.1000575. Epub 2009 Jul 24.
7
Lipocalin 2: a multifaceted modulator of human cancer.脂质运载蛋白2：人类癌症的多面调节因子
Cell Cycle. 2009 Aug;8(15):2347-52. doi: 10.4161/cc.8.15.9224. Epub 2009 Aug 8.
8
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.
9
iNKT cell development is orchestrated by different branches of TGF-beta signaling.iNKT细胞的发育由转化生长因子-β信号传导的不同分支精心调控。
J Exp Med. 2009 Jun 8;206(6):1365-78. doi: 10.1084/jem.20090127. Epub 2009 May 18.
10
Lipocalin 2 promotes breast cancer progression.脂质运载蛋白2促进乳腺癌进展。
Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3913-8. doi: 10.1073/pnas.0810617106. Epub 2009 Feb 23.
Zotero 插件