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Comprehensive analysis of the role of ASC1 and APE2 introns on cellular fitness, transcription, and post-transcriptional dynamics. 综合分析ASC1和APE2内含子在细胞适应性、转录和转录后动力学中的作用。
IF 4.2 Pub Date : 2026-02-01 Epub Date: 2025-10-23 DOI: 10.1111/febs.70294
Emma Fidler, Zulifa Khan, Ahlam Awada, Katherine Dwyer, Susheel Pangeni, Takeshi Sakamoto, Athar Ansari

A splicing-competent intron has been found to affect the expression of a gene at almost every step between transcription and translation. In this investigation, we performed a comprehensive analysis of the role of an intron from two yeast genes, ASC1 and APE2, on cellular fitness and at different steps of gene expression. Mutants containing intronless versions of either gene grew 30-60% slower than their intron-containing counterparts, and their growth was compromised on ethanol and glycerol medium. Furthermore, there was an enhanced R-loop signal in the coding region of both genes in the absence of the intron. Steady-state RNA levels of ASC1 and APE2 decreased by about 30-fold and 5-fold, respectively, in the absence of the intron. Nascent transcription analysis revealed a drop in transcription of both ASC1 and APE2 by 4-10 fold and 2-5 fold, respectively, in the intronless state. The half-life of mRNA of both genes registered a 2- to 3-fold decline in the absence of an intron. A fluorescence in situ hybridization approach detected an increase in nuclear retention of mRNA in the absence of the intron for both genes. Measurement of protein level by western blot found no detectable signal for either protein in the absence of an intron. These results suggest that the introns of both genes affect the expression of their genes at the level of transcription, mRNA stability, and nucleocytoplasmic transport of mRNA. Furthermore, both ASC1 and APE2 introns affect the fitness of cells in terms of growth rate and the ability to grow on different carbon sources.

一个剪接能力的内含子已经被发现影响基因在转录和翻译之间的几乎每一步的表达。在这项研究中,我们对两个酵母基因ASC1和APE2的内含子在细胞适应性和基因表达的不同步骤中的作用进行了全面分析。含有两种基因无内含子版本的突变体比含有内含子版本的突变体生长慢30-60%,并且它们在乙醇和甘油培养基上的生长受到损害。此外,在没有内含子的情况下,两个基因的编码区R-loop信号增强。在没有内含子的情况下,ASC1和APE2的稳态RNA水平分别下降了约30倍和5倍。新生转录分析显示,在无内含子状态下,ASC1和APE2的转录分别下降了4-10倍和2-5倍。在缺少内含子的情况下,两种基因的mRNA的半衰期都下降了2- 3倍。荧光原位杂交方法检测到在两个基因缺少内含子的情况下,mRNA的核保留增加。在缺少内含子的情况下,用western blot检测蛋白质水平,发现两种蛋白质都没有可检测的信号。这些结果表明,这两个基因的内含子在转录、mRNA稳定性和mRNA的核质转运水平上影响其基因的表达。此外,ASC1和APE2内含子都影响细胞的生长速率和在不同碳源上生长的能力。
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引用次数: 0
Hydration-coupled allosteric locking of a phenol- and zinc-free bioactive insulin analog. 无酚和无锌生物活性胰岛素类似物的水合偶联变构锁定。
IF 4.2 Pub Date : 2026-02-01 Epub Date: 2025-10-22 DOI: 10.1111/febs.70283
Esra Ayan, Hiroaki Matsuura, Yoshiaki Kawano, Zain Abhari, Abdullah Kepceoğlu, Takehiko Tosha, Hasan Demirci

Modern insulin still depends on phenol and zinc to keep the hormone stable in vials and pumps, yet both additives slow absorption and raise safety concerns. We therefore asked a simple, clinically driven question: Can we stabilize the fast-acting T-state of insulin without phenol/zinc by exploiting pH-dependent water and anion binding? Using high-resolution synchrotron crystallography (1.4-1.76 Å), we solved novel designer and acid-stable cubic insulin structures from pH 2 to 6 in citrate-sulfate buffers and mapped solvent/anion contacts onto computational analyses. Across the acidic range, we uncovered a conserved 'water-anion clamp' centered on the Phe1ᴮ-Asn3ᴮ pocket that locks insulin in its bioactive T-conformation while neutralizing the protein's positive charge. This clamp: (i) removes the need for phenolic ligands, and (ii) keeps monomers soluble at high concentration. The structural blueprint we provide can guide formulation of phenol- and zinc-free, ultra-rapid insulin for subcutaneous pumps and high-strength cartridges, addressing unmet needs in intensive diabetes management. By clarifying how simple buffer anions and structured water can replace traditional preservatives, our work may link atomic-level detail to a practical therapeutic goal: faster, safer insulin delivery.

现代胰岛素仍然依赖于苯酚和锌来保持小瓶和泵中的激素稳定,但这两种添加剂都减缓了吸收,并引起了安全问题。因此,我们提出了一个简单的,临床驱动的问题:我们能否通过利用ph依赖性水和阴离子结合来稳定胰岛素的速效t状态,而不需要苯酚/锌?利用高分辨率同步加速器晶体学(1.4-1.76 Å),我们在柠檬酸盐-硫酸盐缓冲液中解决了pH为2至6的新型设计和酸稳定的立方胰岛素结构,并将溶剂/阴离子接触映射到计算分析中。在酸性范围内,我们发现了一个保守的“水-阴离子钳”,它以Phe1 -Asn3为中心,将胰岛素锁定在其生物活性的t构象中,同时中和蛋白质的正电荷。这种箝位:(i)消除了对酚类配体的需要,(ii)在高浓度下保持单体可溶。我们提供的结构蓝图可以指导无酚和无锌、用于皮下泵和高强度胰岛素盒的超快速胰岛素的配方,解决糖尿病强化管理中未满足的需求。通过阐明简单的缓冲阴离子和结构水如何取代传统的防腐剂,我们的工作可能将原子水平的细节与实际的治疗目标联系起来:更快,更安全的胰岛素输送。
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引用次数: 0
Psoriasis-like inflammation induces structural and functional changes in mitochondria. 牛皮癣样炎症诱导线粒体的结构和功能改变。
IF 4.2 Pub Date : 2026-02-01 Epub Date: 2025-10-28 DOI: 10.1111/febs.70301
Gabrielė Kulkovienė, Martyna Uldukytė, Sofiya Haluts, Milda Kairytė, Jonas Šoliūnas, Viktorija Šalčiūtė, Rūta Inčiūraitė, Jurgita Skiecevičienė, Monika Iešmantaitė, Ramunė Morkūnienė, Aistė Jekabsone

Mitochondrial structural and functional changes accompany psoriasis, yet the mitochondrial response to psoriatic inflammation in keratinocytes and fibroblasts remains unexplored. In this study, we investigated the effect of psoriasis-like inflammation (PLI) induced by a cytokine cocktail (interleukin (IL)-17A, IL-22 and tumour necrosis factor (TNF)-α) on mitochondrial network morphology and function in cultured keratinocytes (HaCaT) and fibroblasts (BJ-5ta). In both cell types, PLI triggered the expression of psoriasis-related Elafin and high amounts of cytokines (IL-1, IL-6), interferons (IFN-α, IFN-β, IFN-γ), and chemokines (C-C motif chemokine 5 (CCL5) and IL-8), accompanied by increased mitochondrial membrane potential, reactive oxygen species (ROS) production, respiration suppression, network fragmentation, swelling and cristae disassembly. Stimulated emission depletion (STED) nanoscopy revealed the disappearance of mitochondrial cristae in response to PLI, with the process starting more quickly and being more pronounced in keratinocytes than in fibroblasts. These findings highlight cell-specific mitochondrial responses to psoriatic inflammation, guiding future investigations towards new pharmacological targets for managing psoriasis.

银屑病伴随线粒体结构和功能改变,但线粒体对银屑病炎症的反应在角质形成细胞和成纤维细胞中仍未被研究。在这项研究中,我们研究了细胞因子混合物(白细胞介素(IL)-17A、IL-22和肿瘤坏死因子(TNF)-α)诱导的银屑病样炎症(PLI)对培养的角质形成细胞(HaCaT)和成纤维细胞(BJ-5ta)线粒体网络形态和功能的影响。在这两种细胞类型中,PLI触发了银屑病相关的Elafin和大量细胞因子(IL-1、IL-6)、干扰素(IFN-α、IFN-β、IFN-γ)和趋化因子(C-C基元趋化因子5 (CCL5)和IL-8)的表达,并伴有线粒体膜电位升高、活性氧(ROS)产生、呼吸抑制、网络断裂、肿胀和嵴解体。受激辐射耗竭(STED)纳米镜显示,PLI导致线粒体嵴消失,与成纤维细胞相比,这一过程在角质形成细胞中开始得更快、更明显。这些发现强调了细胞特异性线粒体对银屑病炎症的反应,指导了未来研究银屑病治疗的新药理学靶点。
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引用次数: 0
TGFβ enhances platelet-breast-cancer-cell interaction and promotes platelet aggregation. TGFβ增强血小板与乳腺癌细胞的相互作用并促进血小板聚集。
IF 4.2 Pub Date : 2026-02-01 Epub Date: 2025-10-17 DOI: 10.1111/febs.70279
Margherita Genitoni, Lucia Merolle, Agnese Razzoli, Eleonora Maurizi, Gaia Gavioli, Roberto Baricchi, Chiara Marraccini, Davide Schiroli

Platelets (PLTs) have a significant impact on tumor development and progression, particularly in breast cancer, and contribute to cancer-associated thrombosis (CAT). Transforming growth factor beta (TGFβ), which is abundantly secreted by PLTs, is known to promote cancer aggressiveness. Nevertheless, the role of TGFβ in the PLT-cancer-cell interaction is largely unexplored. This study investigates how TGFβ stimulation of MCF7 breast cancer cells affects their capacity to interact with PLTs and induce PLT aggregation. MCF7, pre-treated with TGFβ and then exposed to PLTs, exhibited enhanced epithelial-mesenchymal transition (EMT) and a significantly increased ability to bind PLTs in suspension, as well as to stimulate PLT activation and aggregation. Gene expression and surface protein analyses revealed that TGFβ induced the upregulation of MCF7 adhesion molecules such as integrin-αv/CD51 and galectin-3. Intriguingly, these effects were abolished when cells were plated at high density, suggesting that TGFβ signaling may be influenced by cell junction regulation. Furthermore, we selected specific inhibitors of integrin-αv (cilengitide) and galectin-3 (GB1107) that did not interfere with PLT aggregation itself. Cilengitide, but not GB1107, effectively reduced the increased PLT-MCF7 interaction induced by TGFβ. Both inhibitors, however, significantly diminished PLT aggregation triggered by TGFβ-treated MCF7 cells. Complementary analyses of proteomic datasets from breast cancer tissues demonstrated a significant positive correlation between TGFβ1 and the platelet marker integrin alpha-IIb (ITGA2B; also known as CD41), particularly in luminal A subtypes and in cancers with lymph node involvement. These findings suggest that TGFβ stimulation enhances PLT-breast-cancer cell interactions and promotes PLT aggregation through the upregulation of specific adhesion proteins, thereby potentially contributing to CAT and metastatic progression.

血小板(PLTs)对肿瘤的发生和发展有重要影响,特别是在乳腺癌中,并有助于癌症相关血栓形成(CAT)。转化生长因子β (TGFβ),由plt大量分泌,已知可促进癌症侵袭性。然而,TGFβ在plt -癌细胞相互作用中的作用在很大程度上尚未被探索。本研究探讨TGFβ刺激MCF7乳腺癌细胞如何影响其与PLT相互作用和诱导PLT聚集的能力。用tgf - β预处理MCF7,然后暴露于PLT,表现出增强的上皮-间质转化(EMT)和显著增强的悬浮中结合PLT的能力,以及刺激PLT激活和聚集的能力。基因表达和表面蛋白分析显示,TGFβ诱导MCF7粘附分子如整合素-αv/CD51和半乳糖凝集素-3上调。有趣的是,当细胞被高密度处理时,这些效应被消除,这表明tgf - β信号可能受到细胞连接调节的影响。此外,我们选择了特异性的整合素-αv(西伦吉肽)和半凝集素-3 (GB1107)抑制剂,它们不会干扰PLT本身的聚集。西伦吉肽,而非GB1107,能有效降低TGFβ诱导的PLT-MCF7相互作用。然而,这两种抑制剂都能显著降低tgf β处理的MCF7细胞引发的PLT聚集。来自乳腺癌组织的蛋白质组学数据集的补充分析表明,tgf - β1与血小板标志物整合素α - iib (ITGA2B,也称为CD41)之间存在显著的正相关,特别是在管腔a亚型和淋巴结累及的癌症中。这些发现表明,TGFβ刺激增强了PLT-乳腺癌细胞的相互作用,并通过上调特异性粘附蛋白促进PLT聚集,从而可能促进CAT和转移进展。
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引用次数: 0
Modifying inhibitor specificity for homologous enzymes by machine learning. 通过机器学习修饰抑制剂对同源酶的特异性。
IF 4.2 Pub Date : 2026-02-01 Epub Date: 2025-09-05 DOI: 10.1111/febs.70249
Dor S Gozlan, Reut Meiri, Gili Shapira, Matt Coban, Evette S Radisky, Yaron Orenstein, Niv Papo

Selective inhibitors are essential for targeted therapeutics and for probing enzyme functions in various biological systems. The two main challenges in identifying such protein-based inhibitors lie in the extensive experimental effort required, including the generation of large libraries, and in tailoring the selectivity of inhibitors to enzymes with homologous structures. To address these challenges, machine learning (ML) is being used to improve protein design by training on targeted libraries and identifying key interface mutations that enhance affinity and specificity. However, such ML-based methods are limited by inaccurate energy calculations and difficulties in predicting the structural impacts of multiple mutations. Here, we present an ML-based method that leverages HTS data to streamline the design of selective protease inhibitors. To demonstrate its utility, we applied our new method to find inhibitors of matrix metalloproteinases (MMPs), a family of homologous proteases involved in both physiological and pathological processes. By training ML models on binding data for three MMPs (MMP-1, MMP-3, and MMP-9), we successfully designed a novel N-TIMP2 variant with a differential specificity profile, namely, high affinity for MMP-9, moderate affinity for MMP-3, and low affinity for MMP-1. Our experimental validation showed that this novel variant exhibited a significant specificity shift and enhanced selectivity compared with wild-type N-TIMP2. Through molecular modeling and energy minimization, we obtained structural insights into the variant's enhanced selectivity. Our findings highlight the power of ML-based methods to reduce experimental workloads, facilitate the rational design of selective inhibitors, and advance the understanding of specific inhibitor-enzyme interactions in homologous enzyme systems.

选择性抑制剂对于靶向治疗和探测各种生物系统中的酶功能是必不可少的。鉴定这种基于蛋白质的抑制剂的两个主要挑战在于需要大量的实验工作,包括生成大型文库,以及调整抑制剂对具有同源结构的酶的选择性。为了应对这些挑战,机器学习(ML)正被用于通过训练目标文库和识别增强亲和力和特异性的关键接口突变来改进蛋白质设计。然而,这种基于ml的方法受到能量计算不准确和难以预测多个突变的结构影响的限制。在这里,我们提出了一种基于ml的方法,利用HTS数据来简化选择性蛋白酶抑制剂的设计。为了证明它的实用性,我们应用我们的新方法来寻找基质金属蛋白酶(MMPs)的抑制剂,这是一个参与生理和病理过程的同源蛋白酶家族。通过对三种MMPs (MMP-1、MMP-3和MMP-9)的结合数据进行ML模型训练,我们成功设计了一种新的N-TIMP2变体,它具有不同的特异性,即对MMP-9具有高亲和力,对MMP-3具有中等亲和力,对MMP-1具有低亲和力。我们的实验验证表明,与野生型N-TIMP2相比,这种新变体表现出显著的特异性转移和增强的选择性。通过分子建模和能量最小化,我们获得了变体增强选择性的结构见解。我们的研究结果突出了基于ml的方法在减少实验工作量,促进选择性抑制剂的合理设计以及促进对同源酶系统中特定抑制剂-酶相互作用的理解方面的力量。
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引用次数: 0
Histone demethylases regulate ferroptosis in metabolic dysfunction-associated steatotic liver disease via epigenetic modification. 组蛋白去甲基化酶通过表观遗传修饰调节代谢功能障碍相关脂肪变性肝病中的铁凋亡。
IF 4.2 Pub Date : 2026-02-01 Epub Date: 2025-12-05 DOI: 10.1111/febs.70351
Wentao Huang, Wanqiu Wu, Jiaqi Xiao, Yujie Bai, Chao Chen, Haoxiang Ou, Yaoyao Ma, Xinyu Que, Shigang Shan, Lihua Qu, Li Shen

Ferroptosis, an iron-dependent, non-apoptotic form of cell death, is characterised by pathogenic lipid reactive oxygen species accumulation, dysregulated iron homeostasis, and oxidative stress-induced membrane damage. Numerous studies have demonstrated that ferroptosis plays a critical role in the pathogenesis of metabolic disorders and related cancers, particularly metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatocellular carcinoma. Epigenetic modifications, notably aberrant expression of histone lysine demethylases (KDMs), have been strongly associated with both ferroptosis and MASLD. This review systematically summarises how KDM family members regulate ferroptosis-related gene transcription through epigenetic mechanisms, along with their specific roles in MASLD progression. Additionally, current progress and challenges in the potential application of KDM inhibitors in regulating ferroptosis and MASLD treatment are discussed, with the aim of providing a scientific foundation for the translational development of therapeutic strategies.

铁死亡是一种依赖铁的非凋亡形式的细胞死亡,其特征是致病性脂质活性氧积累、铁稳态失调和氧化应激诱导的膜损伤。大量研究表明,铁下垂在代谢紊乱和相关癌症的发病机制中起着关键作用,特别是代谢功能障碍相关的脂肪变性肝病(MASLD)和肝细胞癌。表观遗传修饰,特别是组蛋白赖氨酸去甲基化酶(kdm)的异常表达,与铁下垂和MASLD密切相关。本文系统综述了KDM家族成员如何通过表观遗传机制调控嗜铁性凋亡相关基因的转录,以及它们在MASLD进展中的具体作用。此外,本文还讨论了KDM抑制剂在调节铁下垂和MASLD治疗中的潜在应用进展和挑战,旨在为治疗策略的转化开发提供科学依据。
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引用次数: 0
Differential regulation of translational stress responses by herpesvirus ubiquitin deconjugases. 疱疹病毒泛素解结剂对翻译应激反应的差异调控。
IF 4.2 Pub Date : 2026-02-01 Epub Date: 2025-10-12 DOI: 10.1111/febs.70278
Jiangnan Liu, Noemi Nagy, Carlos Mario Ayala-Torres, Maria G Masucci

The strategies adopted by viruses to counteract the potential antiviral effects of ribosomal quality control (RQC) that regulates the fidelity of protein translation, ribosome recycling, and the activation of ribosomal and integrated stress responses are poorly understood. Here, we investigated the capacity of the viral ubiquitin deconjugase (vDUB) encoded in the large tegument protein of human pathogenic herpesviruses to interfere with the triggering of RQC upon the induction of translational stress in cytosolic and endoplasmic reticulum (ER)-associated ribosomes. We found that the vDUBs encoded by Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), and Kaposi sarcoma virus (KSHV) share the capacity to counteract the ubiquitination of RPS10, RPS20, and RPS3, and the UFMylation of RPL26 in cells treated with the translation elongation inhibitor anisomycin (ANS), which resulted in the rescue of model RQC and ER-RQC substrates from proteasome- and lysosome-dependent degradation, readthrough of stall-inducing mRNAs, and inhibition of ER-phagy. In contrast, while inhibiting the ubiquitination of RPS10, RPS20, and RPS3, and rescuing RQC substrates almost as efficiently as the homologs, the herpes simplex virus-1 (HSV1) encoded vDUB failed to counteract RPL26 UFMylation. Furthermore, it was unable to rescue the ER-RQC substrate or inhibit ER-phagy, nor did it promote ZAKα phosphorylation or activate the ISR. Our findings pinpoint important differences in the strategies adopted by these human viruses for regulating translational stress responses.

病毒所采用的策略来抵消核糖体质量控制(RQC)的潜在抗病毒作用,RQC调节蛋白质翻译的保真度、核糖体的再循环、核糖体的激活和综合应激反应。在这里,我们研究了人致病性疱疹病毒大被膜蛋白编码的病毒泛素解配酶(vDUB)在诱导胞浆和内质网(ER)相关核糖体翻译应激时干扰RQC触发的能力。我们发现,在翻译延伸抑制剂anisomycin (ANS)处理的细胞中,eb病毒(EBV)、人巨细胞病毒(HCMV)和卡波西肉瘤病毒(KSHV)编码的vDUBs具有抑制RPS10、RPS20和RPS3泛素化以及RPL26的ufmy化的能力,从而使模型RQC和ER-RQC底物免于蛋白酶体和溶酶体依赖的降解,读取诱导失速的mrna,并抑制er吞噬。相比之下,单纯疱疹病毒1 (HSV1)编码的vDUB虽然抑制RPS10、RPS20和RPS3的泛素化,并拯救RQC底物的效率几乎与同源物一样高,但却无法抵消RPL26 UFMylation。此外,它不能拯救ER-RQC底物或抑制er吞噬,也不能促进ZAKα磷酸化或激活ISR。我们的发现指出了这些人类病毒在调节转译应激反应时所采用的策略的重要差异。
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引用次数: 0
Loss of arginase 2 disrupts striatum-specific polyamine homeostasis. 精氨酸酶2的丧失破坏纹状体特异性多胺稳态。
IF 4.2 Pub Date : 2026-02-01 Epub Date: 2025-10-31 DOI: 10.1111/febs.70313
Martyna Nalepa, Omar Basheer, Mariusz Radkiewicz, Katarzyna Skowrońska, Aleksandra Skweres, Aleksandra Owczarek, Agata Dalka, Wojciech Hilgier, Magdalena Zielińska, Emilia Samborowska, Michał Węgrzynowicz

Arginase converts arginine (Arg) to ornithine (Orn), regulating their availability for the metabolic pathways that utilize these amino acids. The roles of arginase isoenzymes, ARG1 and ARG2, vary by cell type, tissue, and physiological state. In the brain, ARG2 is the predominant isoenzyme, particularly enriched in the striatum, where it localizes to a striatum-specific neuronal population-medium spiny neurons (MSNs). While the precise role of ARG2 in MSNs remains unclear, its loss alters the striatal metabolomic profile, highlighting its metabolic significance. Here, to investigate the basis of these complex metabolic changes, we examined Arg metabolism in Arg2 knockout (Arg2-/-) mice. Targeted analysis of Arg-related metabolites and selected proteins regulating Arg metabolic pathways revealed that Arg2 loss significantly increased Arg levels but did not affect Orn, likely due to compensatory synthesis of Orn from Arg (via arginine:glycine amidinotransferase) and/or proline (via ornithine aminotransferase). Additionally, markers of nitric oxide (NO) production remained unchanged, suggesting that striatal ARG2 is not involved in the regulation of this pathway, a role commonly attributed to arginase. Most notably, Arg2 loss disrupted polyamine homeostasis, shifting the balance toward higher polyamines at the expense of lower ones and altering the expression of polyamine-regulating proteins. These findings highlight ARG2's crucial role in striatal metabolism and its potential relevance to striatum-related disorders. Given that striatal ARG2 impairment has been reported in Huntington's disease, a neurodegenerative disorder specifically affecting MSNs, understanding its function may provide insights into the pathology.

精氨酸酶将精氨酸(Arg)转化为鸟氨酸(Orn),调节它们在利用这些氨基酸的代谢途径中的可用性。精氨酸酶同工酶ARG1和ARG2的作用因细胞类型、组织和生理状态而异。在大脑中,ARG2是主要的同工酶,尤其在纹状体中富集,它定位于纹状体特异性神经元群-中棘神经元(msn)。虽然ARG2在msn中的确切作用尚不清楚,但它的缺失改变了纹状体代谢组学特征,突出了其代谢意义。为了研究这些复杂代谢变化的基础,我们检测了Arg2敲除(Arg2-/-)小鼠的Arg代谢。对精氨酸相关代谢物和选定的调节精氨酸代谢途径的蛋白质的针对性分析显示,Arg2的缺失显著增加了精氨酸水平,但不影响Orn,这可能是由于精氨酸(通过精氨酸:甘氨酸氨基转移酶)和/或脯氨酸(通过鸟氨酸氨基转移酶)代偿性合成了Orn。此外,一氧化氮(NO)产生的标记物保持不变,表明纹状体ARG2不参与这一途径的调节,这一作用通常归因于精氨酸酶。最值得注意的是,Arg2的丢失破坏了多胺稳态,以牺牲低多胺为代价,将平衡转向高多胺,并改变了多胺调节蛋白的表达。这些发现强调了ARG2在纹状体代谢中的关键作用及其与纹状体相关疾病的潜在相关性。考虑到纹状体ARG2损伤在亨廷顿氏病(一种特异性影响msn的神经退行性疾病)中有报道,了解其功能可能为病理学提供见解。
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引用次数: 0
Correction to "The chromatin remodeling protein INO80 contributes to the removal of H2A.Z at the p53-binding site of the p21 gene in response to doxorubicin". 更正“染色质重塑蛋白INO80有助于H2A的去除。”Z在p21基因的p53结合位点响应阿霉素”。
IF 4.2 Pub Date : 2026-02-01 Epub Date: 2026-02-11 DOI: 10.1111/febs.70448
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引用次数: 0
Molecular chaperones and proteostasis regulation during cytosolic translation. 细胞质翻译过程中的分子伴侣和蛋白质平衡调节。
IF 4.2 Pub Date : 2026-01-30 DOI: 10.1111/febs.70419
Ulrike Topf

Molecular chaperones ensure that proteins attain their mature state by assisting in proper folding, preventing aggregation, refolding misfolded proteins, and targeting irreparably misfolded proteins for degradation. This comprehensive role is vital for maintaining cellular homeostasis and responding to stress conditions. In this review, I focus on the multifaceted roles of chaperones in regulating protein production, spanning from ribosome biogenesis to controlling translation rate and translation fidelity through the folding of essential translation factors in eukaryotes. I discuss the function of ribosome- and nascent chain-bound molecular chaperones for the translation machinery and protein synthesis. Finally, I highlight findings on the interdependence of the two pillars of protein homeostasis when cells experience cellular stress and organisms face pathophysiological conditions.

分子伴侣通过协助正确折叠、防止聚集、重新折叠错误折叠的蛋白质以及靶向不可修复的错误折叠的蛋白质进行降解来确保蛋白质达到成熟状态。这种全面的作用对于维持细胞稳态和应对应激条件至关重要。在这篇综述中,我重点介绍了伴侣蛋白在调节蛋白质生产中的多方面作用,从核糖体生物发生到通过折叠必要的翻译因子来控制翻译速率和翻译保真度。我讨论了核糖体和新生的链结合分子伴侣在翻译机制和蛋白质合成中的作用。最后,我强调了当细胞经历细胞应激和生物体面临病理生理条件时,蛋白质稳态的两大支柱相互依赖的发现。
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引用次数: 0
期刊
The FEBS journal
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