Biochemical Society transactions最新文献_第2页

Computational modelling of aggressive B-cell lymphoma. 侵袭性b细胞淋巴瘤的计算模型。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-29 DOI: 10.1042/BST20253039

Eleanor S Jayawant, Aimilia Vareli, Andrea Pepper, Chris Pepper, Fabio Simoes, Simon Mitchell

{"title":"Computational modelling of aggressive B-cell lymphoma.","authors":"Eleanor S Jayawant, Aimilia Vareli, Andrea Pepper, Chris Pepper, Fabio Simoes, Simon Mitchell","doi":"10.1042/BST20253039","DOIUrl":"10.1042/BST20253039","url":null,"abstract":"Decades of research into the molecular signalling determinants of B cell fates, and recent progress in characterising the genetic drivers of lymphoma, has led to a detailed understanding of B cell malignancies but also revealed daunting heterogeneity. While current therapies for diffuse large B-cell lymphoma are effective for some patients, they are largely agnostic to the biology of each individual's disease, and approximately one third of patients experience relapsed/refractory disease. Consequently, the challenge is to understand how each patient's mutational burden and tumour microenvironment combine to determine their response to treatment; overcoming this challenge will improve outcomes in lymphoma. This mini review highlights how data-driven modelling, statistical approaches and machine learning are being used to unravel the heterogeneity of lymphoma. We review how mechanistic computational models provide a framework to embed patient data within knowledge of signalling. Focusing on recurrently dysregulated signalling networks in lymphoma (including NF-κB, apoptosis and the cell cycle), we discuss the application of state-of-the-art mechanistic models to lymphoma. We review recent advances in which computational models have demonstrated the power to predict prognosis, identify promising combination therapies and develop digital twins that can recapitulate clinical trial results. With the future of treatment for lymphoma poised to transition from one-size-fits-all towards personalised therapies, computational models are well-placed to identify the right treatments to the right patients, improving outcomes for all lymphoma patients.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"723-735"},"PeriodicalIF":4.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12326154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Engineering protein prenylation: an emerging tool for selective protein modification. 工程蛋白前酰化：一种选择性蛋白质修饰的新兴工具。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-29 DOI: 10.1042/BST20253076

Sneha Venkatachalapathy, Caitlin Lichtenfels, Carston R Wagner, Mark D Distefano

{"title":"Engineering protein prenylation: an emerging tool for selective protein modification.","authors":"Sneha Venkatachalapathy, Caitlin Lichtenfels, Carston R Wagner, Mark D Distefano","doi":"10.1042/BST20253076","DOIUrl":"10.1042/BST20253076","url":null,"abstract":"Prenyltransferases catalyze the attachment of isoprenoids to cysteine residues located near the C-termini of proteins including those containing a 'CaaX' tetrapeptide motif. This enzyme family includes farnesyl transferase (FTase), geranylgeranyltransferase type I (GGTase I), and GGTase type II (GGTase II). The CaaX motif broadly consists of cysteine (C), two aliphatic residues (a), and a variable residue (X), which determines substrate specificity for farnesylation and type I geranylgeranylation. This review primarily focuses on FTase-mediated protein modification strategies for assembling therapeutically valuable proteins. First, the process of protein prenylation and the structural features of the FTase active site are discussed. This is followed by an exploration of FTase-catalyzed bioconjugation of monomeric proteins and peptides, emphasizing its efficiency, modularity, and potential for industrial biological applications. The broader applicability of this approach is then highlighted in the design and assembly of multimeric protein structures, facilitating the development of complex biomolecular architectures with enhanced functionality, stability, and therapeutic potential. Finally, FTase mutagenesis strategies are examined that expand substrate scope, accommodating diverse functional groups for a wide range of biotechnological and therapeutic applications.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 4","pages":"1129-1149"},"PeriodicalIF":4.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12493179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Temporal dynamics of angiogenesis: the emerging role of mechanoregulated pathways. 血管生成的时间动力学：机械调节通路的新作用。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-29 DOI: 10.1042/BST20253048

Shayan Zarin-Bal, Margot Passier, Katie Bentley, Tommaso Ristori

{"title":"Temporal dynamics of angiogenesis: the emerging role of mechanoregulated pathways.","authors":"Shayan Zarin-Bal, Margot Passier, Katie Bentley, Tommaso Ristori","doi":"10.1042/BST20253048","DOIUrl":"10.1042/BST20253048","url":null,"abstract":"Controlling the formation of new blood vessels, i.e. angiogenesis, is a critical challenge for the success of regenerative medicine. The development of effective strategies is hindered by our incomplete understanding of the dynamic mechanisms involved. During physiological angiogenesis, endothelial cells ensure the formation of a functional vascular network by organizing into phenotypic patterns of tip and stalk cells, as mediated by cell-cell signaling communication. While fundamental research identified the major signaling pathways involved in the tip-stalk selection process, recent studies have highlighted the importance of the temporal dynamics of these signaling pathways in determining the final vascular network topology. In this review, we discuss research studies where synergistic approaches between experimental and computational methods led to a renovated understanding of angiogenesis by revealing new temporal regulators of tip-stalk selection. Next, we present increasing evidence suggesting that mechanical cues, such as extracellular matrix stiffness, cyclic strain, and shear stress, are potential temporal regulators of the dynamics of tip-stalk selection and angiogenesis. Future research focused on this promising direction could enable the development of novel approaches that leverage temporal variations of mechanical cues to steer blood vessel growth.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"909-923"},"PeriodicalIF":4.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12410000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The states of senescent cells. 衰老细胞的状态

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-29 DOI: 10.1042/BST20253054

Laura Boose de Mendonça, Guido Lenz, Eduardo Cremonese Filippi-Chiela

{"title":"The states of senescent cells.","authors":"Laura Boose de Mendonça, Guido Lenz, Eduardo Cremonese Filippi-Chiela","doi":"10.1042/BST20253054","DOIUrl":"10.1042/BST20253054","url":null,"abstract":"Senescent cells (SnCs) have typical changes in multiple features, such as increased cellular and nuclear size, morphofunctional alterations in organelles, and high secretory activity. The literature generally groups cellular changes and the non-proliferative character of SnCs into the autonomous senescent phenotype. In contrast, the influence of molecules and extracellular vesicles secreted by SnCs characterizes their non-autonomous phenotype. Unlike the detailed characterization of the structure of SnCs, the discussion regarding SnC states, which are characterized by the comprehensive integration of multiple features a cell harbors in a given moment, is still incipient. This review discusses the possible SnC states (SenStates) and their influence in pathophysiological contexts. We also discuss the main mechanisms and molecular players involved in the establishment and dynamics of these states, such as transcription factors, epigenetic marks, chromatin structure, and others. Finally, we discuss the biological relevance and potential clinical applications of SenStates, as well as open questions in the field.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"935-952"},"PeriodicalIF":4.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

UBQLN2 in neurodegenerative disease: mechanistic insights and emerging therapeutic potential. UBQLN2在神经退行性疾病中的作用机制和新出现的治疗潜力

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-29 DOI: 10.1042/BST20253053

Autumn M Matthews, Alexandra M Whiteley

{"title":"UBQLN2 in neurodegenerative disease: mechanistic insights and emerging therapeutic potential.","authors":"Autumn M Matthews, Alexandra M Whiteley","doi":"10.1042/BST20253053","DOIUrl":"10.1042/BST20253053","url":null,"abstract":"Ubiquilins (UBQLNs) regulate cellular protein turnover by shuttling proteins, or 'clients', to the proteasome or autophagy pathways for degradation. Of the five different UBQLN genes in humans, UBQLN2 is the most highly expressed in the nervous system and muscle tissue and has been linked to multiple neurodegenerative diseases. In particular, point mutations of UBQLN2 cause an X-linked, dominant form of amyotrophic lateral sclerosis (ALS), ALS with frontotemporal dementia (ALS/FTD), or FTD. Failed protein degradation is a hallmark of many neurodegenerative diseases, including ALS and FTD; however, it is not clear exactly how ALS/FTD-associated UBQLN2 mutations contribute to pathogenesis. Recent studies have revealed the complexity of UBQLN2 biology and allow deeper understanding as to how UBQLN2 dysfunction may contribute to neurodegenerative disease. UBQLN2 is necessary for mitochondrial protein degradation and for regulating mitochondrial turnover, both of which are essential for motor neurons and have been implicated in the pathogenesis of ALS. Stress granule (SG) formation and regulation are also affected by UBQLN2 mutations, and their dysregulation may contribute to the toxic protein aggregation and SG changes observed in neurodegenerative disease. Finally, there are compelling links connecting UBQLN2 dysfunction with changes to downstream neuronal morphology, function, and behavior. This review will detail the emerging consensus on how UBQLN2 protects against neurodegenerative disease and will provide insights into potential therapeutic approaches.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"823-833"},"PeriodicalIF":4.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12410002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Emerging drivers of DNA repeat expansions. DNA重复扩增的新兴驱动因素。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-29 DOI: 10.1042/BST20253067

Liangzi Li, W Shem Scott, Sergei M Mirkin

引用次数: 0

Canonical and alternate mechanisms that regulate ubiquitylation by the E3 ligase parkin. E3连接酶激酶调控泛素化的典型和替代机制。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-29 DOI: 10.1042/BST20253050

Nicoletta T Basilone, Viveka M Pimenta, Gary S Shaw

{"title":"Canonical and alternate mechanisms that regulate ubiquitylation by the E3 ligase parkin.","authors":"Nicoletta T Basilone, Viveka M Pimenta, Gary S Shaw","doi":"10.1042/BST20253050","DOIUrl":"10.1042/BST20253050","url":null,"abstract":"Parkin, a Ring-InBetweenRING-Rcat E3 ubiquitin ligase, plays a vital role in the clearance of damaged mitochondria (mitophagy) by ubiquitylating a broad spectrum of mitochondrial proteins. Mutations in the PRKN gene alter parkin ubiquitylation activity and are a leading cause of early-onset Parkinsonism, underlining its critical function in maintaining mitochondrial homeostasis. The structures, substrates, and ubiquitylation mechanisms used by parkin in mitophagy are well established. Yet, early studies as well as more recent proteomics studies identify alternative substrates that reside in the cytosol or other cellular compartments, suggesting potential roles for parkin beyond mitophagy. In addition to its well-documented activation via S65 phosphorylation, numerous other post-translational modifications (PTMs) have been identified in parkin. Some of these modifications have the potential to serve key regulatory mechanisms, perhaps fine-tuning parkin activity or potentially signaling the involvement in alternative cellular pathways beyond mitochondrial quality control. This review examines the canonical mechanism of parkin-mediated ubiquitylation while also exploring alternative regulatory influences that may modulate its enzyme activity. By analyzing emerging evidence on PTMs including phosphorylation, acetylation, ubiquitylation, oxidation, and interaction with alternative activating molecules, we highlight the broader functional landscape of parkin and its implications for cellular stress response.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1053-1065"},"PeriodicalIF":4.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12493190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recent insights into the implications of UGDH mutations for human developmental disease. UGDH突变对人类发育性疾病的影响的最新见解。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-29 DOI: 10.1042/BST20253083

Hali Harwood, Brenna M Zimmer, Asher R Utz, Joseph J Barycki, Melanie A Simpson

引用次数: 0

How does protein aggregate structure affect mechanisms of disaggregation? 蛋白质聚集结构如何影响分解机制？

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-29 DOI: 10.1042/BST20253077

YuChen Yang, Hays S Rye

{"title":"How does protein aggregate structure affect mechanisms of disaggregation?","authors":"YuChen Yang, Hays S Rye","doi":"10.1042/BST20253077","DOIUrl":"10.1042/BST20253077","url":null,"abstract":"Protein misfolding and aggregation underpin numerous pathological conditions, including Alzheimer's, Parkinson's, and Huntington's diseases. Within cells, the competition between protein folding and misfolding-driven aggregation necessitates intricate quality control systems known collectively as the proteostasis network, with molecular chaperones playing central roles. Critical gaps remain in our understanding of why certain protein aggregates are amenable to efficient chaperone-mediated disassembly, while others resist such intervention. Aggregates can be most broadly categorized into structurally ordered amyloid fibrils and more irregular amorphous clusters. Amyloid fibrils are characterized by a highly structured, cross-β-sheet architecture, and they generally display nucleation-driven growth kinetics. In contrast, amorphous aggregates form through heterogeneous interactions among partially unfolded proteins, which typically lack ordered and repeating structure but still display poorly understood, specific assembly constraints. Importantly, amorphous aggregation and amyloid formation are often linked to one another, with several different types of aggregate structures forming at the same time. The ability of molecular chaperones to remodel and disassemble aggregates is affected by aggregate size, internal structure, surface dynamics, and exposure of chaperone-binding sites. However, despite these insights, the mechanistic complexity, aggregate heterogeneity, and dynamic properties present substantial experimental and theoretical challenges. Addressing these challenges will require innovative approaches combining single-molecule biophysics, structural biology, and computational modeling to unveil universal principles governing protein aggregation and disaggregation within cellular environments.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"881-895"},"PeriodicalIF":4.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12410005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Should I stay or should I go: TFIIIC as assembly factor and barrier in RNA polymerase III transcription. 我该走还是该留：TFIIIC作为RNA聚合酶III转录的组装因子和屏障。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-29 DOI: 10.1042/BST20253058

Wolfram Seifert-Davila, Maria Elize van Breugel, Fred van Leeuwen, Christoph W Müller

{"title":"Should I stay or should I go: TFIIIC as assembly factor and barrier in RNA polymerase III transcription.","authors":"Wolfram Seifert-Davila, Maria Elize van Breugel, Fred van Leeuwen, Christoph W Müller","doi":"10.1042/BST20253058","DOIUrl":"10.1042/BST20253058","url":null,"abstract":"Critical for the regulation of eukaryotic gene transcription is the assembly and interplay of general transcription factors (GTFs) with RNA polymerases (RNAPs), leading to the formation of pre-initiation complexes (PICs) as a rate-limiting step in transcription activation. Compared with RNAPII PIC assembly involving many GTFs, activators, and co-activators, RNAPIII PIC assembly is less complex, involving mainly the four GTFs TFIIIA, TFIIIB, TFIIIC, and snRNA activating protein complex with only a few additional factors. The RNAPIII-specific GTF TFIIIC is present in type I and II promoters. One prominent area of investigation has been the dynamic interaction between TFIIIC and its promoter elements, the varying affinities of TFIIIC toward these elements, and the flexible linker within TFIIIC. Additionally, evidence suggests that TFIIIC may play a dual role, acting as an assembly factor that positions TFIIIB during PIC formation and as a barrier during RNAPIII-mediated transcription. By summarizing recent structural, biochemical, and genomic data, this review explores the mechanisms by which RNAPIII-specific GTFs, with a focus on TFIIIC, dynamically regulate RNAPIII transcription.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"925-934"},"PeriodicalIF":4.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0