• 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

非典型GATA转录因子TRPS1通过招募CHD4/NuRD（MTA2）来抑制基因表达，并通过抑制TP63表达来抑制细胞迁移和侵袭。

Atypical GATA transcription factor TRPS1 represses gene expression by recruiting CHD4/NuRD(MTA2) and suppresses cell migration and invasion by repressing TP63 expression.

作者信息

Wang Yuzhi, Lin Xue, Gong Xue, Wu Lele, Zhang Jun, Liu Weiguang, Li Jian, Chen Liming

机构信息

Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of life Science, Nanjing Normal University, 210023, Nanjing, P. R. China.

Institute of Life Science, Southeast University, 210096, Nanjing, P. R. China.

出版信息

Oncogenesis. 2018 Dec 19;7(12):96. doi: 10.1038/s41389-018-0108-9.

DOI:10.1038/s41389-018-0108-9
PMID:30563971
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6299095/
Abstract

Transcriptional repressor GATA binding 1 (TRPS1), an atypical GATA transcription factor, functions as a transcriptional repressor and is also implicated in human cancers. However, the underlying mechanism of TRPS1 contributing to malignancy remains obscure. In the current study, we report that TRPS1 recognizes both gene proximal and distal transcription start site (TSS) sequences to repress gene expression. Co-IP mass spectrometry and biochemical studies showed that TRPS1 binds to CHD4/NuRD(MTA2). Genome-wide and molecular studies revealed that CHD4/NuRD(MTA2) is required for TRPS1 transcriptional repression. Mechanically, TRPS1 and CHD4/NuRD(MTA2) form precision-guided transcriptional repression machinery in which TRPS1 guides the machinery to specific target sites by recognizing GATA elements, and CHD4/NuRD(MTA2) represses the transcription of target genes. Furthermore, TP63 was identified and validated to be a direct target of TRPS1-CHD4/NuRD(MTA2) complex, which represses TP63 expression by involving decommission of TP63 enhancer in the described precision-guided manner, leading to a reduction of the ΔNp63 level and contributing to migration and invasion of cancer cells.

摘要

转录抑制因子GATA结合蛋白1（TRPS1）是一种非典型的GATA转录因子，作为转录抑制因子发挥作用，也与人类癌症有关。然而，TRPS1促成恶性肿瘤的潜在机制仍不清楚。在本研究中，我们报告TRPS1识别基因近端和远端转录起始位点（TSS）序列以抑制基因表达。免疫共沉淀质谱和生化研究表明，TRPS1与CHD4/NuRD（MTA2）结合。全基因组和分子研究表明，TRPS1转录抑制需要CHD4/NuRD（MTA2）。从机制上讲，TRPS1和CHD4/NuRD（MTA2）形成精确引导的转录抑制机制，其中TRPS1通过识别GATA元件将该机制引导至特定靶位点，而CHD4/NuRD（MTA2）抑制靶基因的转录。此外，TP63被鉴定并验证为TRPS1-CHD4/NuRD（MTA2）复合物的直接靶标，该复合物以上述精确引导的方式通过使TP63增强子失活来抑制TP63表达，导致ΔNp63水平降低，并促进癌细胞的迁移和侵袭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f565/6299095/d1ba1fa18173/41389_2018_108_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f565/6299095/c99154d3a92e/41389_2018_108_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f565/6299095/5f3db7daf813/41389_2018_108_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f565/6299095/e4edbb0854fb/41389_2018_108_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f565/6299095/31941e64621a/41389_2018_108_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f565/6299095/6400267e0142/41389_2018_108_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f565/6299095/d1ba1fa18173/41389_2018_108_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f565/6299095/c99154d3a92e/41389_2018_108_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f565/6299095/5f3db7daf813/41389_2018_108_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f565/6299095/e4edbb0854fb/41389_2018_108_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f565/6299095/31941e64621a/41389_2018_108_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f565/6299095/6400267e0142/41389_2018_108_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f565/6299095/d1ba1fa18173/41389_2018_108_Fig6_HTML.jpg

相似文献

1
Atypical GATA transcription factor TRPS1 represses gene expression by recruiting CHD4/NuRD(MTA2) and suppresses cell migration and invasion by repressing TP63 expression.非典型GATA转录因子TRPS1通过招募CHD4/NuRD（MTA2）来抑制基因表达，并通过抑制TP63表达来抑制细胞迁移和侵袭。
Oncogenesis. 2018 Dec 19;7(12):96. doi: 10.1038/s41389-018-0108-9.
2
Transcriptional repression and developmental functions of the atypical vertebrate GATA protein TRPS1.非典型脊椎动物GATA蛋白TRPS1的转录抑制与发育功能
EMBO J. 2001 Apr 2;20(7):1715-25. doi: 10.1093/emboj/20.7.1715.
3
CHD4 mediates SOX2 transcription through TRPS1 in luminal breast cancer.在管腔型乳腺癌中，CHD4通过TRPS1介导SOX2转录。
Cell Signal. 2022 Dec;100:110464. doi: 10.1016/j.cellsig.2022.110464. Epub 2022 Sep 6.
4
CHD3 and CHD4 form distinct NuRD complexes with different yet overlapping functionality.CHD3和CHD4形成具有不同但重叠功能的不同核小体重塑去乙酰化酶复合物。
Nucleic Acids Res. 2017 Oct 13;45(18):10534-10554. doi: 10.1093/nar/gkx711.
5
Sp1 and ETS family transcription factors regulate the mouse Mta2 gene expression.Sp1和ETS家族转录因子调控小鼠Mta2基因的表达。
Gene. 2001 May 2;268(1-2):77-85. doi: 10.1016/s0378-1119(01)00429-2.
6
Transcriptional repressor GATA binding 1-mediated repression of SRY-box 2 expression suppresses cancer stem cell functions and tumor initiation.转录抑制因子 GATA 结合蛋白 1 通过抑制 SRY 盒基因 2 的表达来抑制肿瘤干细胞功能并抑制肿瘤起始。
J Biol Chem. 2018 Nov 30;293(48):18646-18654. doi: 10.1074/jbc.RA118.003983. Epub 2018 Oct 12.
7
NuRD subunit CHD4 regulates super-enhancer accessibility in rhabdomyosarcoma and represents a general tumor dependency.NuRD 亚基 CHD4 调节横纹肌肉瘤中超增强子的可及性，并代表一种普遍的肿瘤依赖性。
Elife. 2020 Aug 3;9:e54993. doi: 10.7554/eLife.54993.
8
Nuclear cathepsin D enhances TRPS1 transcriptional repressor function to regulate cell cycle progression and transformation in human breast cancer cells.细胞核组织蛋白酶D增强TRPS1转录抑制因子功能，以调节人乳腺癌细胞的细胞周期进程和转化。
Oncotarget. 2015 Sep 29;6(29):28084-103. doi: 10.18632/oncotarget.4394.
9
CHD4 is recruited by GATA4 and NKX2-5 to repress noncardiac gene programs in the developing heart.CHD4 通过与 GATA4 和 NKX2-5 相互作用抑制心脏发育过程中非心脏基因的表达。
Genes Dev. 2022 Apr 1;36(7-8):468-482. doi: 10.1101/gad.349154.121. Epub 2022 Apr 21.
10
MTA2/NuRD Regulates B Cell Development and Cooperates with OCA-B in Controlling the Pre-B to Immature B Cell Transition.MTA2/NuRD 调节 B 细胞发育，并与 OCA-B 合作控制前 B 细胞向未成熟 B 细胞的转化。
Cell Rep. 2019 Jul 9;28(2):472-485.e5. doi: 10.1016/j.celrep.2019.06.029.

引用本文的文献

1
Tie2-expressing monocytes/macrophages promote angiogenesis in chronically ischaemic brain tissue.表达Tie2的单核细胞/巨噬细胞促进慢性缺血性脑组织中的血管生成。
Cell Biosci. 2025 May 21;15(1):62. doi: 10.1186/s13578-025-01401-1.
2
TRPS1 maintains luminal progenitors in the mammary gland by repressing SRF/MRTF activity.TRPS1 通过抑制 SRF/MRTF 的活性来维持乳腺腔祖细胞。
Breast Cancer Res. 2024 May 3;26(1):74. doi: 10.1186/s13058-024-01824-7.
3
TRPS1 modulates chromatin accessibility to regulate estrogen receptor alpha (ER) binding and ER target gene expression in luminal breast cancer cells.

本文引用的文献

1
p63 exerts spatio-temporal control of palatal epithelial cell fate to prevent cleft palate.p63对腭上皮细胞命运进行时空控制以预防腭裂。
PLoS Genet. 2017 Jun 12;13(6):e1006828. doi: 10.1371/journal.pgen.1006828. eCollection 2017 Jun.
2
CHD4 Has Oncogenic Functions in Initiating and Maintaining Epigenetic Suppression of Multiple Tumor Suppressor Genes.CHD4在启动和维持多个肿瘤抑制基因的表观遗传抑制中具有致癌功能。
Cancer Cell. 2017 May 8;31(5):653-668.e7. doi: 10.1016/j.ccell.2017.04.005.
3
Interplay between ΔNp63 and miR-138-5p regulates growth, metastasis and stemness of oral squamous cell carcinoma.
TRPS1 调节染色质可及性以调节腔乳腺癌细胞中雌激素受体 α (ER) 的结合和 ER 靶基因表达。
PLoS Genet. 2024 Feb 20;20(2):e1011159. doi: 10.1371/journal.pgen.1011159. eCollection 2024 Feb.
4
TRPS1 regulates the opposite effect of progesterone via RANKL in endometrial carcinoma and breast carcinoma.TRPS1通过RANKL在子宫内膜癌和乳腺癌中调节孕酮的相反作用。
Cell Death Discov. 2023 Jun 21;9(1):185. doi: 10.1038/s41420-023-01484-0.
5
Evidence of epistasis in regions of long-range linkage disequilibrium across five complex diseases in the UK Biobank and eMERGE datasets.在英国生物银行和 eMERGE 数据集的五个复杂疾病的长程连锁不平衡区域中发现了上位性的证据。
Am J Hum Genet. 2023 Apr 6;110(4):575-591. doi: 10.1016/j.ajhg.2023.03.007.
6
TRPS1 Is Differentially Expressed in a Variety of Malignant and Benign Cutaneous Sweat Gland Neoplasms.TRPS1在多种恶性和良性皮肤汗腺肿瘤中表达存在差异。
Dermatopathology (Basel). 2023 Feb 2;10(1):75-85. doi: 10.3390/dermatopathology10010011.
7
A Genome-Wide Association Study Identified Novel Genetic Susceptibility Loci for Oral Cancer in Taiwan.一项全基因组关联研究鉴定了台湾口腔癌的新遗传易感性位点。
Int J Mol Sci. 2023 Feb 1;24(3):2789. doi: 10.3390/ijms24032789.
8
The epigenetic factor CHD4 contributes to metastasis by regulating the EZH2/β-catenin axis and acts as a therapeutic target in ovarian cancer.表观遗传因子 CHD4 通过调节 EZH2/β-catenin 轴促进转移，是卵巢癌的治疗靶点。
J Transl Med. 2023 Jan 21;21(1):38. doi: 10.1186/s12967-022-03854-1.
9
Understanding the development of oral epithelial organs through single cell transcriptomic analysis.通过单细胞转录组分析了解口腔上皮器官的发育。
Development. 2022 Aug 15;149(16). doi: 10.1242/dev.200539. Epub 2022 Aug 17.
10
Paclitaxel Resistance Modulated by the Interaction between TRPS1 and AF178030.2 in Triple-Negative Breast Cancer.TRPS1与AF178030.2相互作用对三阴性乳腺癌中紫杉醇耐药性的调节
Evid Based Complement Alternat Med. 2022 Mar 30;2022:6019975. doi: 10.1155/2022/6019975. eCollection 2022.
ΔNp63与miR-138-5p之间的相互作用调节口腔鳞状细胞癌的生长、转移和干性。
Oncotarget. 2017 Mar 28;8(13):21954-21973. doi: 10.18632/oncotarget.15752.
4
Transposon insertional mutagenesis in mice identifies human breast cancer susceptibility genes and signatures for stratification.小鼠中的转座子插入诱变鉴定出人类乳腺癌易感基因及分层特征。
Proc Natl Acad Sci U S A. 2017 Mar 14;114(11):E2215-E2224. doi: 10.1073/pnas.1701512114. Epub 2017 Mar 1.
5
The p53 family members have distinct roles during mammalian embryonic development.p53家族成员在哺乳动物胚胎发育过程中具有不同的作用。
Cell Death Differ. 2017 Apr;24(4):575-579. doi: 10.1038/cdd.2016.128. Epub 2017 Feb 17.
6
PFKFB3, a Direct Target of p63, Is Required for Proliferation and Inhibits Differentiation in Epidermal Keratinocytes.PFKFB3是p63的直接靶点，对表皮角质形成细胞的增殖是必需的，并抑制其分化。
J Invest Dermatol. 2017 Jun;137(6):1267-1276. doi: 10.1016/j.jid.2016.12.020. Epub 2017 Jan 17.
7
Transposon mutagenesis identifies genes that cooperate with mutant Pten in breast cancer progression.转座子诱变鉴定出在乳腺癌进展中与突变型Pten协同作用的基因。
Proc Natl Acad Sci U S A. 2016 Nov 29;113(48):E7749-E7758. doi: 10.1073/pnas.1613859113. Epub 2016 Nov 14.
8
Regulation of Chondrocyte Survival in Mouse Articular Cartilage by p63.p63 调控小鼠关节软骨中软骨细胞的存活
Arthritis Rheumatol. 2017 Mar;69(3):598-609. doi: 10.1002/art.39976.
9
p63 is required beside p53 for PERP-mediated apoptosis in uveal melanoma.在葡萄膜黑色素瘤中，除了p53外，p63也是PERP介导的细胞凋亡所必需的。
Br J Cancer. 2016 Oct 11;115(8):983-992. doi: 10.1038/bjc.2016.269. Epub 2016 Sep 1.
10
ΔNp63 drives metastasis in breast cancer cells via PI3K/CD44v6 axis.ΔNp63通过PI3K/CD44v6轴驱动乳腺癌细胞转移。
Oncotarget. 2016 Aug 23;7(34):54157-54173. doi: 10.18632/oncotarget.11022.