SAE1

更新于：2024-11-01

基本信息

别名

AOS1、FLJ3091、SAE1

+ [6]

简介

The heterodimer acts as an E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4. It mediates ATP-dependent activation of SUMO proteins followed by formation of a thioester bond between a SUMO protein and a conserved active site cysteine residue on UBA2/SAE2.

关联

100 项与 SAE1 相关的临床结果

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100 项与 SAE1 相关的转化医学

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0 项与 SAE1 相关的专利（医药）

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175

项与 SAE1 相关的文献（医药）

2024-12-01·Cellular and Molecular Life Sciences

Rhes, a striatal enriched protein, regulates post-translational small-ubiquitin-like-modifier (SUMO) modification of nuclear proteins and alters gene expression

Article

作者: Rivera, Oscar ; Karunadharma, Pabalu ; Ramĺrez-Jarquĺn, Uri Nimrod ; McManus, Francis ; Crynen, Gogce ; Bonneil, Eric ; Pierre, Thibault ; Subramaniam, Srinivasa ; Sharma, Manish ; Shahani, Neelam ; Dagar, Sunayana

AbstractRhes (Ras homolog enriched in the striatum), a multifunctional protein that regulates striatal functions associated with motor behaviors and neurological diseases, can shuttle from cell to cell via the formation of tunneling-like nanotubes (TNTs). However, the mechanisms by which Rhes mediates diverse functions remain unclear. Rhes is a small GTPase family member which contains a unique C-terminal Small Ubiquitin-like Modifier (SUMO) E3-like domain that promotes SUMO post-translational modification of proteins (SUMOylation) by promoting “cross-SUMOylation” of the SUMO enzyme SUMO E1 (Aos1/Uba2) and SUMO E2 ligase (Ubc-9). Nevertheless, the identity of the SUMO substrates of Rhes remains largely unknown. Here, by combining high throughput interactome and SUMO proteomics, we report that Rhes regulates the SUMOylation of nuclear proteins that are involved in the regulation of gene expression. Rhes increased the SUMOylation of histone deacetylase 1 (HDAC1) and histone 2B, while decreasing SUMOylation of heterogeneous nuclear ribonucleoprotein M (HNRNPM), protein polybromo-1 (PBRM1) and E3 SUMO-protein ligase (PIASy). We also found that Rhes itself is SUMOylated at 6 different lysine residues (K32, K110, K114, K120, K124, and K245). Furthermore, Rhes regulated the expression of genes involved in cellular morphogenesis and differentiation in the striatum, in a SUMO-dependent manner. Our findings thus provide evidence for a previously undescribed role for Rhes in regulating the SUMOylation of nuclear targets and in orchestrating striatal gene expression via SUMOylation.

2024-08-06·ACS Nano

Nano-Selenium and Glutathione Enhance Cucumber Resistance to Botrytis cinerea by Promoting Jasmonic Acid-Mediated Cucurbitacin Biosynthesis

Article

作者: Fu, Xiaorui ; Jia, Yujiao ; Wu, Yangliu ; Wu, Tong ; Wang, Ping ; Wan, Xiaoying ; Pan, Canping ; Zheng, Shuyang ; Kang, Lu ; Cai, Runze ; Chen, Lanqi ; Yin, Xuebin

Nano-selenium (Nano-Se), as a biological stimulant, promotes plant growth and development, as well as defense against biotic and abiotic stresses. Glutathione (GSH) is a crucial antioxidant and is also involved in the plant defense response to various stresses. In this study, the efficacy of combined treatment of Nano-Se and GSH (SeG) on the resistance of cucumber plants to Botrytis cinerea was investigated in terms of the plant phenotype, gene expression, and levels of accumulated metabolites using transcriptomic and metabolomic analyses. The exogenous application of SeG significantly enhanced plant growth and increased photosynthetic pigment contents and capacity. Notably, B. cinerea infection was reduced markedly by 41.9% after SeG treatment. At the molecular level, the SeG treatment activated the alpha-linolenic acid metabolic pathway and upregulated the expression of genes responsible for jasmonic acid (JA) synthesis, including LOX (210%), LOX4 (430%), AOS1 (100%), and AOC2 (120%), therefore promoting JA accumulation in cucumber. Intriguingly, the level of cucurbitacin, an important phytoalexin in cucurbitaceous plants, was found to be increased in SeG-treated cucumber plants, as was the expression of cucurbitacin biosynthesis-related genes OSC (107.5%), P450 (440.8%,31.6%), and ACT (414.0%). These genes were also upregulated by JA treatment, suggesting that JA may be an upstream regulator of cucurbitacin biosynthesis. Taken together, this study demonstrated that pretreatment of cucumber plants with SeG could activate the JA signaling pathway and promote cucurbitacin biosynthesis to enhance the resistance of the plants to B. cinerea infection. The findings also indicate that SeG is a promising biostimulant for protecting cucumber plants from B. cinerea infection without growth loss.

2024-04-01·Phytomedicine

Ginkgolic acid inhibits the expression of SAE1 and induces ferroptosis to exert an anti-hepatic fibrosis effect

Article

作者: Yang, Ruining ; Du, Gang ; Liu, Zeyang ; Liu, Kao ; Zhang, Sai ; Hao, Wenjuan ; Jiang, Zhaochen ; Jin, Bin ; Xia, Tong ; Liu, Mingkun ; Xu, Qianqian ; Li, Jianghong

BACKGROUNDFinding a drug for early intervention in the hepatic fibrosis process has important clinical significance. Previous studies have suggested SUMOylation as a potential target for intervention in hepatic fibrosis. However, the role of SAE1, a marker of SUMOylation, in hepatic fibrosis is unknown. Additionally, whether ginkgolic acid (GA), a SUMOylation inhibitor, inhibits hepatic fibrosis by inhibiting SUMO1-activating enzyme subunit 1 (SAE1) should be further investigated.METHODSLiver tissues of patients with hepatic cirrhosis and a rat model of hepatic fibrosis constructed with CCl₄ (400 mg/kg, twice weekly) or TAA (200 mg/kg, twice weekly) were selected, and the degree of hepatic fibrosis was then evaluated using H&E, Sirius red, and Masson's trichrome staining. After knockdown or overexpression of SAE1 in hepatic stellate cells, the expression levels of ferroptosis and hepatic fibrosis markers were measured in vitro. After intervention with a ferroptosis inhibitor, the expression levels were again measured in vivo and in vitro.RESULTSWe first demonstrated that SAE1 increased in patients with hepatic cirrhosis. Subsequently, testing of the rat hepatic fibrosis model confirmed that GA reduced the expression of SAE1 and improved hepatic fibrosis in rats. Then, we used hepatic stellate cell lines to confirm in vitro that GA inhibited SAE1 expression and induced ferroptosis, and that overexpression of SAE1 or inhibition of ferroptosis reversed this process. Finally, we confirmed in vivo that GA induced ferroptosis and alleviated the progression of hepatic fibrosis, while inhibiting ferroptosis also reversed the progression of hepatic fibrosis in rats.CONCLUSIONSAE1 is a potential anti-fibrotic target protein, and GA induces ferroptosis of hepatic stellate cells by targeting SAE1 to exert an anti-hepatic fibrosis effect, which lays an experimental foundation for the future clinical application of its anti-hepatic fibrosis effect.

项与 SAE1 相关的新闻（医药）

2022-07-27

·生物谷

J Clin Invest: KRAS基因突变是胰腺癌细胞外小泡淋巴管生成的重要启动子

该研究提供了对癌症淋巴管生成的机制洞察，具有开发生物标记物和RAS途径疗法的潜力。胰腺癌是最致命的胃肠道恶性肿瘤，是癌症相关死亡的第四大原因，五年生存率最低，仅为11%。由于缺乏筛查方法和早期症状的缺乏，胰腺癌最常在晚期被发现-当时几乎没有可用的治疗选择。主要的组织学类型是胰腺导管腺癌(PDAC)，90%以上的病例携带KRAS基因突变作为分子标志。作为胰腺癌的驱动基因，KRAS基因改变促进了胰腺上皮异型增生、胰腺上皮内瘤变和胰腺粘液瘤的发生发展。直到最近，由于设计特定抑制剂的结构困难，KRAS突变被认为是不可药物的靶点。图片来源: https://doi-org.libproxy1.nus.edu.sg/10.1172/JCI161454. 近日，来自罗马尼亚的研究者们在J Clin Invest杂志上发表了题为“KRAS mutations as essential promoters of lymphangiogenesis via extracellular vesicles in pancreatic cancer”的文章，该研究提供了对癌症淋巴管生成的机制洞察，具有开发生物标记物和RAS途径疗法的潜力。柯尔斯滕鼠肉瘤病毒(KRAS)基因突变存在于90%以上的胰腺导管腺癌(PDAC)中。KrasG12D是最常见的改变，促进癌前病变，并与更具侵袭性的表型相关。这些肿瘤具有瘤内淋巴管网络增多和频繁的淋巴转移。罗、李等人探讨了KrasG12D突变与PDAC淋巴管生成的关系。作者使用体外和体内模型和一种优雅的机制方法来描述促进淋巴管生成的另一种途径。KrasG12D通过SAE1和SUMO2的激活诱导异源核糖核蛋白A1(HnRNPA1)的SUMO化。 SUMOylated hnRNPA1被负载到细胞外小泡(EVS)中，并被人内皮淋巴细胞(HLEC)内化。此外，SUMOylated hnRNPA1通过稳定PROX1的mRNA，促进淋巴管生成和LN转移。 KrasG12D诱导PDAC淋巴管生成的可能机制图片来源: https://doi-org.libproxy1.nus.edu.sg/10.1172/JCI161454. 综上所述，本研究揭示了KrasG12D PDAC中肿瘤诱导淋巴管发育和早期LN转移的分子机制。作者发现KrasG12D蛋白是血管内皮生长因子-C非依赖性诱导淋巴管生成的重要因素。在机制上，KrasG12D在激活依赖于SAE1的hnRNPA1的SUMO化和随后的EV负载方面发挥了作用，从而进一步诱导了HLEC中PROX1的激活。（生物谷 Bioon.com）参考文献 Radu Pirlog et al. KRAS mutations as essential promoters of lymphangiogenesis via extracellular vesicles in pancreatic cancer. J Clin Invest. 2022 Jul 15;132(14):e161454. doi: 10.1172/JCI161454.

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