Biological Chemistry最新文献_第2页

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 Print Date: 2025-03-26 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":"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":"89-100"},"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 Print Date: 2025-03-26 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":"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":"101-115"},"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

Unclogging of the TOM complex under import stress. 在进口压力下疏通TOM复合体。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-03-28 DOI: 10.1515/hsz-2025-0110

Joshua Jackson, Thomas Becker

{"title":"Unclogging of the TOM complex under import stress.","authors":"Joshua Jackson, Thomas Becker","doi":"10.1515/hsz-2025-0110","DOIUrl":"https://doi.org/10.1515/hsz-2025-0110","url":null,"abstract":"Mitochondrial functions and biogenesis depend on the import of more than 1,000 proteins which are synthesized as precursor proteins on cytosolic ribosomes. Mitochondrial protein translocases sort the precursor proteins into the mitochondrial sub-compartments: outer and inner membrane, the intermembrane space and the matrix. The translocase of the outer mitochondrial membrane (TOM complex) constitutes the major import site for most of these precursor proteins. Defective protein translocases, premature folding of the precursor, or depletion of the membrane potential can cause clogging of the TOM channel by a precursor protein. This clogging impairs further protein import and leads to accumulation of precursor proteins in the cell that perturbates protein homeostasis, leading to proteotoxic stress in the cell. Therefore, unclogging of the translocon is critical for maintaining mitochondrial and cellular function. Ubiquitylation and AAA-ATPases play a central role in the extraction of the precursor proteins to deliver them to the proteasome for degradation. Here we summarize our understanding of the molecular mechanisms that remove such translocation-stalled precursor proteins from the translocation channel to regenerate the TOM complex for protein import.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727981","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

Exploring the biological potential of the brominated indenoindole MC11 and its interaction with protein kinase CK2. 探索溴化吲哚 MC11 的生物潜力及其与蛋白激酶 CK2 的相互作用。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-03-24 Print Date: 2025-03-26 DOI: 10.1515/hsz-2024-0160

Christelle Marminon, Christian Werner, Alexander Gast, Lars Herfindal, Johana Charles, Dirk Lindenblatt, Dagmar Aichele, Angélique Mularoni, Stein Ove Døskeland, Joachim Jose, Karsten Niefind, Marc Le Borgne

{"title":"Exploring the biological potential of the brominated indenoindole MC11 and its interaction with protein kinase CK2.","authors":"Christelle Marminon, Christian Werner, Alexander Gast, Lars Herfindal, Johana Charles, Dirk Lindenblatt, Dagmar Aichele, Angélique Mularoni, Stein Ove Døskeland, Joachim Jose, Karsten Niefind, Marc Le Borgne","doi":"10.1515/hsz-2024-0160","DOIUrl":"10.1515/hsz-2024-0160","url":null,"abstract":"Protein kinase CK2 is a promising therapeutic target, especially in oncology. Over the years, various inhibitors have been developed, with polyhalogenated scaffolds emerging as a particularly effective class. Halogens like bromine and chlorine enhance inhibitor stability by forming additional interactions within the ATP pocket. Among halogenated scaffolds, benzotriazole and benzimidazole have led to potent molecules such as 4,5,6,7-tetrabromo-1H-benzotriazole (IC50 = 300 nM) and 4,5,6,7-tetrabromo-2-(dimethylamino)benzimidazole (IC50 = 140 nM). Modifications, including 4,5,6-tribromo-7-ethyl-1H-benzotriazole (IC50 = 160 nM), further improved activity. Changing scaffolds while retaining halogens has enabled design of new inhibitors. Flavonols, dibenzofuranones, and the indeno[1,2-b]indole scaffold are key examples. Halogenation of the reference molecule 5-isopropyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione (4b, IC50 = 360 nM) significantly boosted potency. The study focused on introducing four halogens, yielding to the compound 1,2,3,4-tetrabromo-5-isopropyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione (MC11), with an IC50 of 16 nM. Co-crystallography revealed how bromine atoms enhance binding, and MC11 demonstrated strong in cellulo activity, particularly against leukemic cell lines like IPC-Bcl2.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"125-138"},"PeriodicalIF":2.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669027","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

GPI-anchored serine proteases: essential roles in development, homeostasis, and disease. gpi锚定丝氨酸蛋白酶：在发育、体内平衡和疾病中的重要作用。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-03-17 Print Date: 2025-01-29 DOI: 10.1515/hsz-2024-0135

Joseph G Lundgren, Michael G Flynn, Karin List

引用次数: 0

Unfolded protein responses in Chlamydomonas reinhardtii. 莱茵衣藻对未折叠蛋白的响应。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-03-13 DOI: 10.1515/hsz-2025-0101

Sarah Gabelmann, Michael Schroda

{"title":"Unfolded protein responses in Chlamydomonas reinhardtii.","authors":"Sarah Gabelmann, Michael Schroda","doi":"10.1515/hsz-2025-0101","DOIUrl":"https://doi.org/10.1515/hsz-2025-0101","url":null,"abstract":"The disruption of protein homeostasis leads to the increased un- and misfolding of proteins and the formation of toxic protein aggregates. Their accumulation triggers an unfolded protein response that is characterized by the transcriptional upregulation of molecular chaperones and proteases, and aims to restore proteome integrity, maintain cellular function, suppress the cause of perturbation, and prevent disease and death. In the green microalga Chlamydomonas reinhardtii, the study of this response to proteotoxic stress has provided insights into the function of chaperone and protease systems, which are, though simpler, closely related to those found in land plants. In addition, there has been considerable progress in understanding the triggers and regulation of compartment-specific unfolded protein responses. This review provides an overview on how the dysfunction of protein homeostasis is sensed in the different compartments of Chlamydomonas, and summarizes the current knowledge on the pathways that are triggered to restore equilibrium in the cell, while also highlighting similarities and differences to the unfolded protein responses of other model organisms.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603840","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