Biochemical Society transactions最新文献

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

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-07-04 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":"https://doi.org/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":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Straight A's: protein acylation in the S-activation and autophagic degradation of NOD-like receptors. 直接A: s活化和nod样受体自噬降解中的蛋白酰化。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-07-04 DOI: 10.1042/BST20253026

Noah R Martin, Gregory D Fairn

{"title":"Straight A's: protein acylation in the S-activation and autophagic degradation of NOD-like receptors.","authors":"Noah R Martin, Gregory D Fairn","doi":"10.1042/BST20253026","DOIUrl":"https://doi.org/10.1042/BST20253026","url":null,"abstract":"Over the past decade, S-acylation has emerged as a crucial regulator of several innate immune signaling pathways, with new insights continually being gained. S-acylation, a reversible post-translational modification, involves the attachment of fatty acyl chains to cysteine residues, influencing protein localization, function, and stability. In this mini-review, we examine the accumulating evidence of the role of S-acylation in regulating nucleotide oligomerization domain (NOD)-like receptors. NOD-like receptor subfamily P3 (NLRP3), a key player in inflammasome formation, undergoes S-acylation at specific cysteine residues, which are essential for its localization to the trans-Golgi network and other organelles. Various zinc finger Asp-His-His-Cys motif-containing (zDHHC) enzymes mediate this modification, with zDHHC5 being particularly important for activation and the ability of NLRP3 to interact with never in mitosis gene A (NIMA)-related protein kinase 7 (NEK7), promoting inflammasome assembly, caspase-1 activation, and pyroptosis. Alternatively, S-acylation by zDHHC12 targets NLRP3 for chaperone-mediated autophagy, preventing excessive inflammation. NOD2, another NLR, requires S-acylation for membrane localization and effective signaling via the NF-κB and mitogen-activated protein kinase pathways in response to peptidoglycan components. Dysregulation of S-acylation in NOD2 is associated with Crohn's Disease (hypo-acylated) and Blau syndrome/early-onset sarcoidosis (hyper-acylated). Soluble NOD2 lacking S-acylation is ubiquitinated and eliminated by the autophagic pathway. This review highlights the significance of understanding the S-acylation cycle and its regulatory mechanisms in developing potential therapeutic interventions for related inflammatory diseases. We also discuss unresolved questions regarding the S-acylation of NOD2 and NLRP3, as well as the regulation of S-acylation in general.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Molecular insight on the role of the phosphoinositide PIP3 in regulating the protein kinases Akt, PDK1, and BTK. 磷酸肌肽PIP3在调节蛋白激酶Akt， PDK1和BTK中的分子作用。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-07-04 DOI: 10.1042/BST20253059

Alexandria L Shaw, John E Burke

{"title":"Molecular insight on the role of the phosphoinositide PIP3 in regulating the protein kinases Akt, PDK1, and BTK.","authors":"Alexandria L Shaw, John E Burke","doi":"10.1042/BST20253059","DOIUrl":"https://doi.org/10.1042/BST20253059","url":null,"abstract":"Protein kinases are master regulators of myriad processes in eukaryotic cells playing critical roles in growth, metabolism, cellular differentiation, and motility. A subclass of protein kinases is regulated by their ability to be localized and activated by the phosphoinositide phosphatidylinositol (3,4,5)-trisphosphate (PIP3). This includes multiple members of the AGC and TEC family kinases, which contain PIP3 binding pleckstrin homology (PH) domains. It has been postulated that they can be activated by PIP3-mediated disruption of autoinhibitory interactions between their kinase domains and PH domains. There has been considerable controversy based on differing molecular models for how these kinases are regulated by lipid binding and post-translational modifications. This review focuses on understanding the molecular underpinnings for how the PH domains of these enzymes regulate kinase activity and what role PIP3 plays in pathway activation. A specific focus is on the integration of experimental data derived from X-ray crystallography, cryo-electron microscopy, and hydrogen deuterium exchange mass spectrometry along with recent advances in artifical intelligence enabled protein modeling. The main lipid-binding enzymes described are the AGC protein kinases 3-phosphoinositide-dependent kinase (PDK1) and Akt, and the TEC family kinase, Bruton's agammaglobulinemia tyrosine kinase (BTK).","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Insights into the synchronization between DNA replication and parental histone recycling. DNA复制和亲本组蛋白循环同步的见解。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-06-30 DOI: 10.1042/BST20253014

Xiaorong Tang, Yuan Yao, Gang Li, Haiyun Gan

引用次数: 0

Insights into the role of collided ribosomes during the activation of the integrated stress response. 在综合应激反应的激活过程中碰撞核糖体的作用。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-06-30 DOI: 10.1042/BST20253034

Ankanahalli N Nanjaraj Urs, Lucas Kim, Hani S Zaher

{"title":"Insights into the role of collided ribosomes during the activation of the integrated stress response.","authors":"Ankanahalli N Nanjaraj Urs, Lucas Kim, Hani S Zaher","doi":"10.1042/BST20253034","DOIUrl":"10.1042/BST20253034","url":null,"abstract":"Mechanisms that regulate and reprogram gene expression are particularly important under stress conditions. The integrated stress response (ISR) signaling pathway is one such pro-survival and adaptive mechanism conserved in eukaryotes. The ISR is characterized by the activation of protein kinases that phosphorylate the eukaryotic initiation factor 2α (eIF2α) in response to several stress conditions, including nutrient deprivation, viral infection, and protein misfolding. Phosphorylation of eIF2α results in global inhibition of translation, while promoting the translation of a few pro-survival genes. Here, we focus on the mechanism of activation of the eIF2α kinase general control nonderepressible 2 (Gcn2). The protein was initially discovered in yeast more than four decades ago, and it was proposed to respond to amino acid starvation through the accumulation of deacylated tRNAs. However, more recent studies have changed our understanding of its activation and suggest a direct role for ribosome stalling and collisions in the process. In this review, we discuss the classical model for the tRNA-mediated activation of GCN2 and the recent shift in this model to accommodate the observations that wide-ranging translational stresses trigger its activation.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"615-626"},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Mechanisms of heme transport in the mitochondria. 线粒体中血红素运输的机制。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-06-30 DOI: 10.1042/BST20253013

Saieeda Fabia Ali, Adrianna E White, Amy Medlock, Oleh Khalimonchuk

引用次数: 0

Emerging tools and methods to study cell signalling mediated by branched ubiquitin chains. 研究分支泛素链介导的细胞信号传导的新兴工具和方法。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-06-30 DOI: 10.1042/BST20253015

Matthew R McFarland, Yogesh Kulathu

引用次数: 0

Single-molecule localisation microscopy approaches reveal envelope glycoprotein clusters in single-enveloped viruses: a potential functional role? 单分子定位显微镜方法揭示单包膜病毒的包膜糖蛋白簇：潜在的功能作用？

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-06-30 DOI: 10.1042/BST20240769

David J Williamson, Cecilia Zaza, Irene Carlon-Andres, Tobias Starling, Alessia Gentili, Joseph W Thrush, Audrey Le Bas, Ravi Teja Ravi, Stuart Neil, Ray J Owens, Maud Dumoux, Sabrina Simoncelli, Sergi Padilla-Parra

{"title":"Single-molecule localisation microscopy approaches reveal envelope glycoprotein clusters in single-enveloped viruses: a potential functional role?","authors":"David J Williamson, Cecilia Zaza, Irene Carlon-Andres, Tobias Starling, Alessia Gentili, Joseph W Thrush, Audrey Le Bas, Ravi Teja Ravi, Stuart Neil, Ray J Owens, Maud Dumoux, Sabrina Simoncelli, Sergi Padilla-Parra","doi":"10.1042/BST20240769","DOIUrl":"10.1042/BST20240769","url":null,"abstract":"Understanding how viruses enter and fuse with host cells is crucial for developing effective antiviral therapies. The process of viral entry and fusion involves a series of complex steps that allow the virus to breach the host cell membrane and deliver its genetic material inside, with viral fusogens often co-operating to attain the required energy for successful membrane fusion. This co-operative clustering of fusogens in viral envelopes is similar to receptor clustering in cellular systems, where receptors aggregate to initiate signalling cascades. Single-molecule localisation microscopy (SMLM) approaches have emerged as powerful tools to study these intricate mechanisms, allowing the observation of proteins with unprecedented levels of detail. These technologies provide unparalleled insights into the dynamics of viral entry and fusion at a molecular level, revealing how the co-ordinated action of fusogens facilitates membrane fusion. By employing the newest advances in SMLM techniques, such as DNA-PAINT and MINFLUX, we anticipate that precise information on the key steps of viral fusion can be revealed with high spatial and temporal resolutions, identifying critical points in the process that can be targeted by antiviral strategies.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"643-652"},"PeriodicalIF":3.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Is the SPLUNC1-Orai1 axis a critical determinant of lung health? SPLUNC1-Orai1轴是肺健康的关键决定因素吗？

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-06-30 DOI: 10.1042/BST20241029

Robert Tarran

引用次数: 0

Understanding carboxysomes to enhance carbon fixation in crops. 了解羧酶体促进作物固碳的作用。

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-06-30 DOI: 10.1042/BST20253072

Nghiem Dinh Nguyen, Loraine M Rourke, Alexandra Cleaver, Joseph Brock, Benedict M Long, Dean G Price

引用次数: 0