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Triple SELEX approach for the selection of a highly specific RNA aptamer binding homoeriodictyol. 三重SELEX方法选择高特异性RNA适体结合同源碘二醇。
IF 2.9 4区 生物学
Biological Chemistry Pub Date : 2025-06-03 DOI: 10.1515/hsz-2025-0118
Janis Hoetzel, Cristina Bofill-Bosch, Andres W Martinez, Martin M Rudolph, Florian Groher, Beatrix Suess
{"title":"Triple SELEX approach for the selection of a highly specific RNA aptamer binding homoeriodictyol.","authors":"Janis Hoetzel, Cristina Bofill-Bosch, Andres W Martinez, Martin M Rudolph, Florian Groher, Beatrix Suess","doi":"10.1515/hsz-2025-0118","DOIUrl":"https://doi.org/10.1515/hsz-2025-0118","url":null,"abstract":"<p><p>The application of synthetic riboswitches or aptamer-based biosensors for the monitoring of engineered metabolic pathways greatly depends on a high degree of target molecule specificity. Since metabolic pathways include close derivatives that often differ only in single moieties, the binding specificity of aptamers utilized for these systems has to be high. In the present study, we selected an RNA aptamer that is highly specific in its binding to homoeriodictyol while discriminating its close derivatives eriodictyol and naringenin. This high degree in specificity was achieved through three consecutive SELEX approaches while the selection parameters were adjusted and refined from one to the next. The adjustments along the process, with the selection outcome and next-generation sequencing analysis of the selection rounds, led to valuable insights into the stringency necessary to facilitate target specificity in aptamers obtained from SELEX. From the third selection, we obtained a highly binding specific aptamer and examined its structure and binding properties. Overall, our results connect the importance of selection stringency with SELEX outcome and aptamer specificity while providing a highly selective, homoeriodictyol-binding RNA aptamer.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
70 years of CK2: still exciting, essential - and enigmatic! 70年的CK2:仍然令人兴奋,必不可少和神秘!
IF 2.9 4区 生物学
Biological Chemistry Pub Date : 2025-06-03 DOI: 10.1515/hsz-2025-0147
Karsten Niefind, Claudia Götz, Joachim Jose
{"title":"70 years of CK2: still exciting, essential - and enigmatic!","authors":"Karsten Niefind, Claudia Götz, Joachim Jose","doi":"10.1515/hsz-2025-0147","DOIUrl":"https://doi.org/10.1515/hsz-2025-0147","url":null,"abstract":"","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The mitochondrial intermembrane space - a permanently proteostasis-challenged compartment. 线粒体膜间空间-一个永久性蛋白酶抑制的隔室。
IF 2.9 4区 生物学
Biological Chemistry Pub Date : 2025-05-27 DOI: 10.1515/hsz-2025-0108
Matthias Weith, Konstantin Weiss, Dylan Stobbe, Jan Riemer
{"title":"The mitochondrial intermembrane space - a permanently proteostasis-challenged compartment.","authors":"Matthias Weith, Konstantin Weiss, Dylan Stobbe, Jan Riemer","doi":"10.1515/hsz-2025-0108","DOIUrl":"https://doi.org/10.1515/hsz-2025-0108","url":null,"abstract":"<p><p>The mitochondrial intermembrane space (IMS) houses proteins essential for redox regulation, protein import, signaling, and energy metabolism. Protein import into the IMS is mediated by dedicated pathways, including the disulfide relay pathway for oxidative folding. In addition, various IMS-traversing import pathways potentially expose unfolded proteins, representing threats to proteostasis. This trafficking of precursors coincides with unique biophysical challenges in the IMS, including a confined volume, elevated temperature, variable pH and high levels of reactive oxygen species. Ultrastructural properties and import supercomplex formation ameliorate these challenges. Nonetheless, IMS proteostasis requires constant maintenance by chaperones, folding catalysts, and proteases to counteract misfolding and aggregation. The IMS plays a key role in stress signaling, where proteostasis disruptions trigger responses including the integrated stress response (ISR) activated by mitochondrial stress (ISRmt) and responses to cytosolic accumulation of mitochondrial protein precursors. This review explores the biology and mechanisms governing IMS proteostasis, presents models, which have been employed to decipher IMS-specific stress responses, and discusses open questions.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
TBK1 alleviates triptolide-induced nephrotoxic injury by up-regulating mitophagy in HK2 cells. TBK1通过上调HK2细胞的线粒体自噬来减轻雷公藤甲素引起的肾毒性损伤。
IF 2.9 4区 生物学
Biological Chemistry Pub Date : 2025-05-07 DOI: 10.1515/hsz-2024-0141
Xinxin Lu, Qionghui Huang, Zhaohui He, Huanjie Zhou, Zhenwei Chen, Youjian Zhou, Tiecheng Yang, Lang-Jing Zhu
{"title":"TBK1 alleviates triptolide-induced nephrotoxic injury by up-regulating mitophagy in HK2 cells.","authors":"Xinxin Lu, Qionghui Huang, Zhaohui He, Huanjie Zhou, Zhenwei Chen, Youjian Zhou, Tiecheng Yang, Lang-Jing Zhu","doi":"10.1515/hsz-2024-0141","DOIUrl":"https://doi.org/10.1515/hsz-2024-0141","url":null,"abstract":"<p><p><i>Tripterygium wilfordii</i> has been used for a long time to treat autoimmune diseases. Its toxic side effects limit its clinical application. Mitophagy plays a protective role in various diseases. TANK-binding kinase 1 (TBK1) is a mitophagy-promoting molecule. This study aimed to investigate whether TBK1 could alleviate triptolide (TP)-induced nephrotoxicity by regulating mitophagy. To establish TP-induced nephrotoxic injury in animal model, 16 Sprague-Dawley rats were administered with TP by gavage, then renal tissues were collected for hematoxylin and eosin (HE) staining, western blotting and immunofluorescence analysis. To investigate whether up-regulation of TBK1 could alleviate TP-induced nephrotoxic injury and the specific mechanism, HK-2 cells were cultured <i>in vitro</i>, transfected with TBK1-overexpression recombinant lentivirus, then treated with TP. Western blotting, immunofluorescence, flow cytometry, multifunctional microplate detector were used to detect the relevant molecules. Here we found that TP caused kidney function damage, declined mitophagy levels, decreased the expression of TBK1 and mitophagy-related proteins in rats. TP stimulation decreased cell viability, mitochondrial membrane potential, mitophagy-protein, the formation of mito-autophagosomes and mito-autophagolysosomes in HK-2 cells. Upregulating TBK1 could reverse these damages. In summary, TP-induced cell injury had decreased mitophagy levels. Up-regulating TBK1 could increase mitophagy and further alleviate TP-induced cell injury.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CK2 control of human papillomavirus life cycles. CK2对人乳头瘤病毒生命周期的控制。
IF 2.9 4区 生物学
Biological Chemistry Pub Date : 2025-05-05 DOI: 10.1515/hsz-2024-0150
Apurva T Prabhakar, Iain M Morgan
{"title":"CK2 control of human papillomavirus life cycles.","authors":"Apurva T Prabhakar, Iain M Morgan","doi":"10.1515/hsz-2024-0150","DOIUrl":"https://doi.org/10.1515/hsz-2024-0150","url":null,"abstract":"<p><p>Human papillomaviruses are causative agents in around 5 % of all cancers, and in a number of other human diseases. While prophylactic vaccines will alleviate the HPV disease burden on future generations, there are currently no therapeutic anti-viral strategies for combating HPV infections or lesions. HPV induce the proliferation of infected epithelial cells and modulate the host differentiation response, and both of these controls are required for a successful viral life cycle. Enhanced understanding of viral-host interactions during the viral life cycle will identify potential novel anti-viral strategies for therapeutic development. This minireview will summarize the critical role of the host enzyme CK2 in regulating the function of the viral proteins E1, E2 and E7; such control makes CK2 a critical enzyme for regulating HPV life cycles. Therapeutic strategies blocking CK2 function to combat HPV infections and treat HPV diseases will be described.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pathogenic missense variants of CSNK2B associated with Poirier-Bienvenu neurodevelopmental disorder impact differently on CK2 holoenzyme formation. 与Poirier-Bienvenu神经发育障碍相关的CSNK2B致病性错义变异对CK2全酶形成的影响不同。
IF 2.9 4区 生物学
Biological Chemistry Pub Date : 2025-05-05 DOI: 10.1515/hsz-2024-0162
Hanna Kavaliova, Barbara Lecis, Demetra Ballardin, Laetitia Cobret, Thierry Bienvenu, Severine Morisset-Lopez, Heike Rebholz
{"title":"Pathogenic missense variants of CSNK2B associated with Poirier-Bienvenu neurodevelopmental disorder impact differently on CK2 holoenzyme formation.","authors":"Hanna Kavaliova, Barbara Lecis, Demetra Ballardin, Laetitia Cobret, Thierry Bienvenu, Severine Morisset-Lopez, Heike Rebholz","doi":"10.1515/hsz-2024-0162","DOIUrl":"https://doi.org/10.1515/hsz-2024-0162","url":null,"abstract":"<p><p>Poirier-Bienvenu neurodevelopmental syndrome is a neurodevelopmental disorder associated with <i>de novo</i> variants of the <i>CSNK2B</i> gene, characterized by intellectual disability, developmental delay, frequent seizures and more. While the majority of variants are nonsense variants leading to abortion of protein translation and no or truncated CK2β, many pathogenic missense variants also exist. We investigated the effect of four variants on CK2 holoenzyme formation and activity. We show that variants in the Zinc-finger region leads to reduced protein stability and altered subcellular localization. The instability is partly mediated by proteasomal and lysosomal degradation. We further show that homodimerization of these CK2β variants (p.Arg111Pro, p.Cys137Phe), localized within the Zinc-finger domain, is significantly reduced, while CK2α binding appears not affected. Other variants, p.Asp32Asn and p.Arg86Cys, did not affect stability or CK2β/α binding. For these mutants, the key to understanding the pathological mechanism may depend on external factors, such as altered protein-protein interaction. We conclude that Zinc-finger domain variants appear to destabilize the protein and affect holoenzyme formation, effectively reducing the pool of competent holoCK2. In the context of POBINDS, our findings suggest that Zinc-finger domain variants are likely to affect cells similarly to truncating and splicing variants with reduced translation of full-length CK2β.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The evolution and diversification of the Hsp90 co-chaperone system. Hsp90共伴蛋白系统的演化与多样化。
IF 2.9 4区 生物学
Biological Chemistry Pub Date : 2025-04-23 DOI: 10.1515/hsz-2025-0112
Sonja Engler, Johannes Buchner
{"title":"The evolution and diversification of the Hsp90 co-chaperone system.","authors":"Sonja Engler, Johannes Buchner","doi":"10.1515/hsz-2025-0112","DOIUrl":"https://doi.org/10.1515/hsz-2025-0112","url":null,"abstract":"<p><p>The molecular chaperone Hsp90 is the central element of a chaperone machinery in the cytosol of eukaryotic cells that is characterized by a large number of structurally and functionally different co-chaperones that influence the core chaperone component in different ways and increase its influence on the proteome. From yeast to humans, the number of Hsp90 co-chaperones has increased from 14 to over 40, and new co-chaperones are still being discovered. While Hsp90 itself has only undergone limited changes in structure and mechanism from yeast to humans, its increased importance and contribution to different processes in humans is based on the evolution and expansion of the cohort of co-chaperones. In this review, we provide an overview of Hsp90 co-chaperones, focusing on their roles in regulating Hsp90 function and their evolution from yeast to humans.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Time- and dose-dependent effects of CIGB-300 on the proteome of lung squamous cell carcinoma. CIGB-300对肺鳞状细胞癌蛋白质组的时间和剂量依赖性影响。
IF 2.9 4区 生物学
Biological Chemistry Pub Date : 2025-04-23 DOI: 10.1515/hsz-2024-0149
Liudy García-Hernández, Lingfeng Dai, Arielis Rodríguez-Ulloa, Ying Yi, Luis J González, Vladimir Besada, Wen Li, Silvio E Perea, Yasser Perera
{"title":"Time- and dose-dependent effects of CIGB-300 on the proteome of lung squamous cell carcinoma.","authors":"Liudy García-Hernández, Lingfeng Dai, Arielis Rodríguez-Ulloa, Ying Yi, Luis J González, Vladimir Besada, Wen Li, Silvio E Perea, Yasser Perera","doi":"10.1515/hsz-2024-0149","DOIUrl":"https://doi.org/10.1515/hsz-2024-0149","url":null,"abstract":"<p><p>Proteome-wide scale in a dose - and time-depending setting is crucial to fully understand the pharmacological mechanism of anticancer drugs as well as identification of candidates for drug response biomarkers. Here, we investigated the effect of the CIGB-300 anticancer peptide at IC<sub>50</sub> and IC<sub>80</sub> doses during 1 and 4 h of treatment on the squamous lung cancer cell (NCI-H226) proteome. An overwhelming dose-dependent inhibitory effect with minor up-regulated proteins was observed by increasing CIGB-300 dose level. Functional enrichment was also CIGB-300 dose-dependent with common or exclusively regulated proteins in each dose and time settings. A protein core involving small molecule biosynthesis, aldehyde metabolism and metabolism of nucleobases was regulated irrespectively to the dose or the treatment time. Importantly, a group of proteins linked to NSCLC tumor biology, poor clinical outcome and some Protein Kinase CK2 substrates, were significantly regulated by treating with both CIGB-300 doses. Likewise, we observed a consistent downregulation of different proteins that had been already reported to be inhibited by CIGB-300 in lung adenocarcinoma and acute myeloid leukemia. Overall, our proteomics-guided strategy based on time and drug dose served to uncover novel clues supporting the CIGB-300 cytotoxic effect and also to identify putative pharmacodynamic biomarkers in NSCLC.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The mitochondrial unfolded protein response: acting near and far. 线粒体未折叠蛋白反应:远近作用。
IF 2.9 4区 生物学
Biological Chemistry Pub Date : 2025-04-17 DOI: 10.1515/hsz-2025-0107
Nikolaos Charmpilas, Qiaochu Li, Thorsten Hoppe
{"title":"The mitochondrial unfolded protein response: acting near and far.","authors":"Nikolaos Charmpilas, Qiaochu Li, Thorsten Hoppe","doi":"10.1515/hsz-2025-0107","DOIUrl":"https://doi.org/10.1515/hsz-2025-0107","url":null,"abstract":"<p><p>Mitochondria are central hubs of cellular metabolism and their dysfunction has been implicated in a variety of human pathologies and the onset of aging. To ensure proper mitochondrial function under misfolding stress, a retrograde mitochondrial signaling pathway known as UPR<sup>mt</sup> is activated. The UPR<sup>mt</sup> ensures that mitochondrial stress is communicated to the nucleus, where gene expression for several mitochondrial proteases and chaperones is induced, forming a protective mechanism to restore mitochondrial proteostasis and function. Importantly, the UPR<sup>mt</sup> not only acts within cells, but also exhibits a conserved cell-nonautonomous activation across species, where mitochondrial stress in a defined tissue triggers a systemic response that affects distant organs. Here, we summarize the molecular basis of the UPR<sup>mt</sup> in the invertebrate model organism <i>Caenorhabditis elegans</i> and in mammals. We also describe recent findings on cell-nonautonomous activation of the UPR<sup>mt</sup> in worms, flies and mice, and how UPR<sup>mt</sup> activation in specific tissues affects organismal metabolism and longevity.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Back to the basics: the molecular blueprint of plant heat stress transcription factors. 回到基础:植物热胁迫转录因子的分子蓝图。
IF 2.9 4区 生物学
Biological Chemistry Pub Date : 2025-04-14 DOI: 10.1515/hsz-2025-0115
Sotirios Fragkostefanakis, Enrico Schleiff, Klaus-Dieter Scharf
{"title":"Back to the basics: the molecular blueprint of plant heat stress transcription factors.","authors":"Sotirios Fragkostefanakis, Enrico Schleiff, Klaus-Dieter Scharf","doi":"10.1515/hsz-2025-0115","DOIUrl":"https://doi.org/10.1515/hsz-2025-0115","url":null,"abstract":"<p><p>Heat stress transcription factors (HSFs) play a pivotal role in regulating plant responses to heat and other environmental stresses, as well as developmental processes. HSFs possess conserved domains responsible for DNA binding, oligomerization, and transcriptional regulation, which collectively enable precise and dynamic control of cellular responses to environmental stimuli. Functional diversification of HSFs has been demonstrated through genetic studies in model plants such as <i>Arabidopsis thaliana</i> and economically important crops like tomato, rice, and wheat. However, the underlying molecular mechanisms that govern HSF function remain only partially understood, and for a handful of HSFs. Advancements in structural biology, biochemistry, molecular biology, and genomics shed light into how HSFs mediate stress responses at the molecular level. These insights offer exciting opportunities to leverage HSF biology for gene editing and crop improvement, enabling the customization of stress tolerance traits via regulation of HSF-dependent regulatory networks to enhance thermotolerance. This review synthesizes current knowledge on HSF structure and function, providing a perspective on their roles in plant adaptation to a changing climate.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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