Biological Chemistry最新文献

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":"Tripterygium wilfordii 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 in vitro, 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.","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

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":"Poirier-Bienvenu neurodevelopmental syndrome is a neurodevelopmental disorder associated with de novo variants of the CSNK2B 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.","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

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":"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 IC50 and IC80 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.","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

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":"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 Arabidopsis thaliana 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.","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

The proteostasis burden of aneuploidy. 非整倍体的蛋白质抑制负担。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-04-14 DOI: 10.1515/hsz-2024-0163

Prince Saforo Amponsah, Zuzana Storchová

引用次数: 0

A CK2α' mutant indicating why CK2α and CK2α', the isoforms of the catalytic subunit of human protein kinase CK2, deviate in affinity to CK2β. 人类蛋白激酶CK2催化亚基的同工型CK2α和CK2α′对CK2β的亲和力偏离的原因是CK2α突变体。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-04-14 DOI: 10.1515/hsz-2024-0157

Christian Werner, Sophia Eimermacher, Hugo Harasimowicz, Dietmar Fischer, Markus Pietsch, Karsten Niefind

{"title":"A CK2α' mutant indicating why CK2α and CK2α', the isoforms of the catalytic subunit of human protein kinase CK2, deviate in affinity to CK2β.","authors":"Christian Werner, Sophia Eimermacher, Hugo Harasimowicz, Dietmar Fischer, Markus Pietsch, Karsten Niefind","doi":"10.1515/hsz-2024-0157","DOIUrl":"https://doi.org/10.1515/hsz-2024-0157","url":null,"abstract":"Protein kinase CK2 (casein kinase 2) mainly exists as heterotetrameric holoenzyme with two catalytic subunits (CK2α or CK2α') bound to a homodimer of non-catalytic subunits (CK2β). With CSNK2A1 and CSNK2A2, the human genome contains two paralogs encoding catalytic CK2 subunits. Both gene products, called CK2α and CK2α', strongly interact with CK2β. An earlier report that CK2α' has a lower CK2β affinity than CK2α is confirmed via isothermal titration calorimetry in this study. Furthermore, we show with a fluorescence-anisotropy assay that a CK2β-competitive peptide binds less strongly to CK2α' than to CK2α. The reason for the reduced affinity of CK2α' to CK2β and CK2β competitors is puzzling: both isoenzymes have identical amino acid compositions at their CK2β interfaces, but the β4β5 loop, a component of this interface, is conformationally less adaptable in CK2α' than in CK2α due to intramolecular constraints. To release these constraints, we constructed a CK2α' mutant that was equalized to CK2α at the backside of the β4β5 loop. Concerning thermostability, affinity to CK2β or CK2β competitors and 3D-structure next to the β4β5 loop, this CK2α' mutant is more similar to CK2α than to its own wild-type, suggesting a critical role of the β4β5 loop adaptability for CK2β affinity.","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":"143952940","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 nascent polypeptide-associated complex (NAC) as regulatory hub on ribosomes. 新生多肽相关复合体（NAC）作为核糖体的调控中心。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-04-02 DOI: 10.1515/hsz-2025-0114

Laurenz Rabl, Elke Deuerling

引用次数: 0