更新于：2024-09-19

EYA3

更新于：2024-09-19

基本信息

别名

DKFZp686C132、EYA transcriptional coactivator and phosphatase 3、EYA3

+ [1]

简介

Tyrosine phosphatase that specifically dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph). 'Tyr-142' phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress. Promotes efficient DNA repair by dephosphorylating H2AX, promoting the recruitment of DNA repair complexes containing MDC1 (PubMed:19234442, PubMed:19351884). Its function as histone phosphatase probably explains its role in transcription regulation during organogenesis. Coactivates SIX1, and seems to coactivate SIX2, SIX4 and SIX5. The repression of precursor cell proliferation in myoblasts by SIX1 is switched to activation through recruitment of EYA3 to the SIX1-DACH1 complex and seems to be dependent on EYA3 phosphatase activity (By similarity). May be involved in development of the eye.

关联

100 项与 EYA3 相关的临床结果

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100 项与 EYA3 相关的转化医学

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0 项与 EYA3 相关的专利（医药）

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项与 EYA3 相关的文献（医药）

2024-07-02·ChemBioChem

Thermal Proteome Profiling Reveals Insight to Antiproliferative and Pro‐Apoptotic Effects of Lagunamide A in the Modulation of DNA Damage Repair

Article

作者: Sieber, Stephan A ; Zahler, Stefan ; Braig, Simone ; Kazmaier, Uli ; Vollmar, Angelika M ; Mostert, Dietrich ; Andler, Oliver ; Zischka, Hans ; Orgler, Christina ; Hu, Yudong

AbstractLagunamide A is a biologically active natural product with a yet unidentified molecular mode of action. Cellular studies revealed that lagunamide A is a potent inhibitor of cancer cell proliferation, promotes apoptosis and causes mitochondrial dysfunction. To decipher the cellular mechanism responsible for these effects, we utilized thermal protein profiling (TPP) and identified EYA3 as a stabilized protein in cells upon lagunamide A treatment. EYA3, involved in the DNA damage repair process, was functionally investigated via siRNA based knockdown studies and corresponding effects of lagunamide A on DNA repair were confirmed. Furthermore, we showed that lagunamide A sensitized tumor cells to treatment with the drug doxorubicin highlighting a putative therapeutic strategy.

2024-07-01·Molecular and Cellular Endocrinology

Photoperiod, but not progesterone, has a strong impact upon the transcriptome of the medio-basal hypothalamus in female goats and ewes

Article

作者: Dardente, Hugues ; Lasserre, Olivier ; Lomet, Didier ; Gonzalez, Anne-Alicia ; Beltramo, Massimiliano ; Robert, Vincent ; Mialhe, Xavier

Photoperiod is the main environmental driver of seasonal responses in organisms living at temperate and polar latitudes. Other external cues such as food and temperature, and internal cues including hormones, intervene to fine-tune phasing of physiological functions to the solar year. In mammals, the medio-basal hypothalamus (MBH) is the key integrator of these cues, which orchestrates a wide array of seasonal functions, including breeding. Here, using RNAseq and RT-qPCR, we demonstrate that molecular components of the photoperiodic response previously identified in ewes are broadly conserved in does (female goats, Capra hircus), with a common core of ∼50 genes. This core group can be defined as the "MBH seasonal trancriptome", which includes key players of the pars tuberalis-tanycytes neuroendocrine retrograde pathway that governs intra-MBH photoperiodic switches of triiodothyronine (T3) production (Tshb, Eya3, Dio2 and SlcO1c1), the two histone methyltransferases Suv39H2 and Ezh2 and the secreted protein Vmo1. Prior data in ewes revealed that T3 and estradiol (E2), both key hormones for the proper timing of seasonal breeding, differentially impact the MBH seasonal transcriptome, and identified cellular and molecular targets through which these hormones might act. In contrast, information regarding the potential impact of progesterone (P4) upon the MBH transcriptome was nonexistent. Here, we demonstrate that P4 has no discernible transcriptional impact in either does or ewes. Taken together, our data show that does and ewes possess a common core set of photoperiod-responsive genes in the MBH and conclusively demonstrate that P4 is not a key regulator of the MBH transcriptome.

2024-07-01·Journal of Biological Chemistry

Biochemical characterization of the Eya and PP2A-B55α interaction

Article

作者: Zhao, Rui ; Hughes, Connor J ; Ahn, Natalie G ; Li, Xueni ; Ford, Heide L ; Anderson, Ryan ; Ebmeier, Chris ; Alderman, Christopher ; Wagley, Marisa E ; Zhang, Lingdi

The eyes absent (Eya) proteins were first identified as co-activators of the six homeobox family of transcription factors and are critical in embryonic development. These proteins are also re-expressed in cancers after development is complete, where they drive tumor progression. We have previously shown that the Eya3 N-terminal domain (NTD) contains Ser/Thr phosphatase activity through an interaction with the protein phosphatase 2A (PP2A)-B55α holoenzyme and that this interaction increases the half-life of Myc through pT58 dephosphorylation. Here, we showed that Eya3 directly interacted with the NTD of Myc, recruiting PP2A-B55α to Myc. We also showed that Eya3 increased the Ser/Thr phosphatase activity of PP2A-B55α but not PP2A-B56α. Furthermore, we demonstrated that the NTD (∼250 amino acids) of Eya3 was completely disordered, and it used a 38-residue segment to interact with B55α. In addition, knockdown and phosphoproteomic analyses demonstrated that Eya3 and B55α affected highly similar phosphosite motifs with a preference for Ser/Thr followed by Pro, consistent with Eya3's apparent Ser/Thr phosphatase activity being mediated through its interaction with PP2A-B55α. Intriguingly, mutating this Pro to other amino acids in a Myc peptide dramatically increased dephosphorylation by PP2A. Not surprisingly, Myc^P59A, a naturally occurring mutation hotspot in several cancers, enhanced Eya3-PP2A-B55α-mediated dephosphorylation of pT58 on Myc, leading to increased Myc stability and cell proliferation, underscoring the critical role of this phosphosite in regulating Myc stability.

项与 EYA3 相关的新闻（医药）

2023-05-29

·生物谷

第四军医大学晏贤春团队揭示了miR-342-5p是治疗缺血性疾病的潜在靶点

血管生成，即从现有血管形成新的血管，涉及内皮细胞(ECs)的增殖、分化和迁移。血管生成，即从现有血管形成新的血管，涉及内皮细胞(ECs)的增殖、分化和迁移。随着生长的血管新生芽融合，内皮细胞获得动脉表型并进一步成熟，最终形成稳定的分级血管网络，通过一个称为动脉化的过程向组织灌流。动脉化失败会导致血管畸形和功能障碍，包括遗传性出血性毛细血管扩张症(HHT)和脑海绵状血管畸形(CCM)，因此有必要阐明EC动脉化的分子机制。图片来源：https://doi-org.libproxy1.nus.edu.sg/10.1016/j.omtn.2023.03.022. 近日，来自第四军医大学晏贤春团队的研究者们在Molecular Therapy: Nucleic Acids杂志上发表了题为“miR-342-5p downstream to Notch enhances arterialization of endothelial cells in response to shear stress by repressing MYC”的文章，该研究揭示了miR-342-5p是一种机械性miR，它介导了切应力激活的Notch对EC动脉化的影响，是治疗缺血性疾病的潜在靶点。在血管发育过程中，血管内皮细胞(ECs)在遗传程序和剪应力触发的机械转导作用下发生动脉化，形成稳定的血管系统。虽然Notch受体是已知的感觉切应力和促进内皮细胞动脉化的受体，但其下游机制尚不清楚。在本研究中，发现Notch下游的miR-342-5p对剪应力有反应，并促进EC的动脉化。切应力以Notch依赖的方式上调人脐静脉内皮细胞miR-342-5p。MIR-342-5P的过表达上调了剪切力相关的转录信号。此外，在Matrigel Plug实验和视网膜血管生成模型中，miR-342-5p上调动脉标志物并促进EC动脉化。相反，miR-342-5p基因敲除下调了动脉标志物，损害了视网膜动脉化，并部分消除了切应力和Notch激活诱导的动脉标志物上调。在机制上，miR-342-5p的过表达抑制MYC，抑制EC的增殖，促进动脉化，这是通过靶向EYA3促进MYC蛋白降解实现的。一致认为，EYA3的过表达挽救了miR-342-5p介导的MYC下调和EC动脉化。在体后肢缺血模型中，结扎动脉中miR-342-5p的表达显著降低，肌肉注射miR-3425p可促进EC动脉化，改善血流灌注。 MIR-342促进血管内皮细胞动脉化和增加后肢缺血模型的血液灌注量图片来源：https://doi-org.libproxy1.nus.edu.sg/10.1016/j.omtn.2023.03.022. 本研究结果揭示了剪切力和Notch3介导的内皮动脉化的机制，即miR-342作为机械miR介导剪切力-Notch信号轴通过直接靶向EYA3下调MYC来促进内皮动脉化。因此，miR-342可能成为治疗缺血性疾病的潜在靶点。（生物谷 Bioon.com）参考文献 Xiaoyan Zhang et al. miR-342-5p downstream to Notch enhances arterialization of endothelial cells in response to shear stress by repressing MYC. Mol Ther Nucleic Acids. 2023 Apr 4;32:343-358. doi: 10.1016/j.omtn.2023.03.022.

临床结果临床1期申请上市临床终止

2023-04-17

·生物谷

第四军医大学的研究者揭示了miR-342-5p是缺血性疾病的潜在治疗靶点

血管生成，即从现有血管形成新血管，涉及内皮细胞的增殖、分化和迁移。在生长的血管生成芽融合后，内皮细胞获得动脉表型并经历进一步成熟，最终形成一个稳定的分级血管网络，通过一个称为动脉化的过程灌注组织。血管生成，即从现有血管形成新血管，涉及内皮细胞的增殖、分化和迁移。在生长的血管生成芽融合后，内皮细胞获得动脉表型并经历进一步成熟，最终形成一个稳定的分级血管网络，通过一个称为动脉化的过程灌注组织。动脉化失败会导致血管畸形和功能障碍，包括遗传性出血性毛细血管扩张症（HHT）和脑海绵状畸形（CCM）。因此，有必要阐明内皮细胞（EC）动脉化的分子机制。图片来源：https://doi-org.libproxy1.nus.edu.sg/10.1016/j.omtn.2023.03.022 近日，来自第四军医大学的研究者们在Molecular Therapy: Nucleic Acid杂志上发表了题为“miR-342-5p downstream to Notch enhances arterialization of endothelial cells in response to shear stress by repressing MYC via targeting EYA3”的文章，该研究表明miR-342-5p介导剪切应力激活的Notch对EC动脉化的影响，是缺血性疾病的潜在治疗靶点。在血管发育过程中， EC在遗传程序和剪切应力触发的机械转导的反应下进行动脉化，形成稳定的血管系统。尽管Notch受体已知能感知剪切应力并促进EC动脉化，但其下游机制尚不清楚。研究者发现Notch下游miR-342-5p对剪切应力有反应，并促进EC动脉化。剪切应力在HUVECs中以Notch依赖的方式上调miR-342-5p。miR-342-5p过表达上调了剪切应力相关的转录组特征。此外，在Matrigel栓塞试验和视网膜血管生成模型中，miR-342-5p上调动脉标志物并促进EC动脉化。相反，miR-342-5p敲低下调了动脉标志物，损害了视网膜动脉化，并部分消除了剪切应力和Notch激活诱导的动脉标志物上调。从机制上讲，miR-342-5p过表达抑制MYC以抑制EC增殖并促进动脉化，这是通过靶向EY A3促进MYC蛋白降解来实现的。一致地，EY A3过表达挽救了miR-342-5p介导的MYC下调和EC动脉化。在体内，在后肢缺血模型中，miR-342-5p在结扎动脉中的表达显著降低，肌肉注射miR-342-5p促进EC动脉化和改善灌注。 Notch下游的miR-342-5p通过靶向EYA3抑制MYC，增强内皮细胞对剪切应力的动脉化反应. 图片来源：https://doi-org.libproxy1.nus.edu.sg/10.1016/j.omtn.2023.03.022 综上所述，该研究结果揭示了剪切应力和Notch介导的内皮动脉化的潜在机制，即miR-342作为一种机械miR介导剪切应力Notch信号轴，通过直接靶向EY A3下调MYC来促进内皮动脉化。因此，miR-342可能是治疗缺血性疾病的潜在靶点。（生物谷 Bioon.com）参考文献 Xiaoyan Zhang et al. miR-342-5p downstream to Notch enhances arterialization of endothelial cells in response to shear stress by repressing MYC via targeting EYA3. Molecular Therapy: Nucleic Acid. 31 March 2023. https://doi-org.libproxy1.nus.edu.sg/10.1016/j.omtn.2023.03.022