Biochemical Society transactions最新文献_第2页

Fc-engineering for improved cancer immunotherapy. 改进癌症免疫治疗的fc工程。

IF 4.4 3区生物学

Biochemical Society transactions Pub Date : 2026-08-26 DOI: 10.1042/BST20250554

Ella Borgman, Camille Le Gall, Hidde Ploegh, Novalia Pishesha

引用次数: 0

Functional amyloids as molecular switches: emerging roles in diverse signalling pathways. 作为分子开关的功能性淀粉样蛋白：在不同信号通路中的新角色。

IF 4.4 3区生物学

Biochemical Society transactions Pub Date : 2026-08-26 DOI: 10.1042/BST20250193

Jessica A Buchanan, Brayden C Williams, Megan Steain, Margaret Sunde

{"title":"Functional amyloids as molecular switches: emerging roles in diverse signalling pathways.","authors":"Jessica A Buchanan, Brayden C Williams, Megan Steain, Margaret Sunde","doi":"10.1042/BST20250193","DOIUrl":"10.1042/BST20250193","url":null,"abstract":"Across all domains of life, functional amyloid fibrils serve structural, storage and signalling functions. In signalling pathways, assembly into the amyloid state constitutes a rapid and cooperative molecular switch that can reorganise protein function, promote multivalent interactions, and amplify downstream responses through templated self-propagation. Advances in the understanding of functional amyloids as regulators of signalling highlight their tailored structural properties and biological consequences. The nucleation-dependent polymerisation of amyloid enables sensitive control over activation thresholds, while the repetitive fibrillar architecture concentrates functional domains to enhance avidity and cooperativity. Controlled mechanisms for assembly, compartmentalisation and reversibility prevent inappropriate persistence or activity. These features underpin diverse signalling systems, including the RIPK1:RIPK3 necrosome in mammalian necroptosis, fungal prion-based cell-death pathways and prion-like regulatory systems in yeast and metazoans that modulate translation, development and cellular memory. Functional amyloids represent a versatile and evolutionarily conserved mechanism for molecular signalling and offer opportunities for the design of programmable amyloid-based switches with potential applications in therapeutics and synthetic biology.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 8","pages":"1131-1143"},"PeriodicalIF":4.4,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811917","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

Beyond the scaffold: extracellular matrix uptake in breast cancer. 支架之外：乳腺癌的细胞外基质摄取。

IF 4.4 3区生物学

Biochemical Society transactions Pub Date : 2026-07-29 DOI: 10.1042/BST20250121

Elena Rainero

{"title":"Beyond the scaffold: extracellular matrix uptake in breast cancer.","authors":"Elena Rainero","doi":"10.1042/BST20250121","DOIUrl":"10.1042/BST20250121","url":null,"abstract":"Breast cancer is associated with a highly fibrotic tumour microenvironment, where cancer-associated fibroblasts (CAFs) secrete excessive amounts of extracellular matrix (ECM). Fibrosis and collagen deposition correlate with poor patient survival, indicating that the ECM plays a role in promoting tumorigenesis. The ECM is constantly remodelled through extracellular and intracellular degradation pathways. While protease-dependent extracellular ECM degradation has been well studied, the intracellular degradation pathway is less understood. Here, I will describe the evidence supporting a role for ECM internalisation and lysosomal degradation in promoting breast cancer progression. Both cancer cells and CAFs are reported to uptake ECM components via different ECM receptors. These include TEM8 in fibroblasts, Endo180 in both cancer cells and CAFs, and α2β1 integrin in cancer cells. Importantly, this process has been associated with metabolic reprogramming under nutrient deprivation conditions representative of the breast cancer TME, cancer cell growth in vitro and in vivo, and cancer cell migration and invasion. Therefore, regulators of ECM endocytosis and lysosomal delivery might represent novel potential targets to prevent tumour growth and metastasis in ECM-rich breast cancers.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 7","pages":"915-922"},"PeriodicalIF":4.4,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13358726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403440","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

TDP-43 proteinopathy as a biomarker and therapeutic target in amyotrophic lateral sclerosis. TDP-43蛋白病变作为肌萎缩侧索硬化症的生物标志物和治疗靶点。

IF 4.4 3区生物学

Biochemical Society transactions Pub Date : 2026-07-29 DOI: 10.1042/BST20260896

Eleni Christoforidou, Emily McFagan, Martha McLaughlin, Majid Hafezparast

{"title":"TDP-43 proteinopathy as a biomarker and therapeutic target in amyotrophic lateral sclerosis.","authors":"Eleni Christoforidou, Emily McFagan, Martha McLaughlin, Majid Hafezparast","doi":"10.1042/BST20260896","DOIUrl":"10.1042/BST20260896","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is the most common form of adult-onset motor neuron disease, characterised by the degeneration of upper and lower motor neurons. The cytoplasmic aggregation of TDP-43 (TAR DNA-binding protein 43), an RNA-binding protein, is considered a hallmark of ALS pathology, found in nearly all postmortem cases of ALS. TDP-43 is normally primarily nuclear, where it has a widespread role in gene regulation. Mutations, extrinsic stressors, and alterations in RNA homeostasis in ALS lead to nuclear depletion of TDP-43 and the formation of cytosolic TDP-43 aggregates. This causes multiple downstream effects on neuronal function and degeneration as well as gene expression. TDP-43 is a promising target as a biomarker, as it is found to be elevated in the biofluids of ALS patients, and its cytoplasmic aggregation can also be observed in peripheral tissues; however, methodological variability and technical limitations currently preclude the establishment of TDP-43 as a standalone biomarker. There are also promising therapeutic strategies in development targeting TDP-43 pathology, but a critical challenge that remains is achieving a balance between eliminating toxic aggregates and preserving the essential functions of TDP-43. In summary, with further research, considering TDP-43 pathology in ALS gives hope for finding future novel diagnostics and therapeutics for ALS.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 7","pages":"901-913"},"PeriodicalIF":4.4,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13329289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359194","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

Implications of Rho GTPase signaling in cancer immunotherapy. Rho GTPase信号在癌症免疫治疗中的意义。

IF 4.4 3区生物学

Biochemical Society transactions Pub Date : 2026-07-29 DOI: 10.1042/BST20260485

Mingjun Cai, Fukun Guo, Yi Zheng

{"title":"Implications of Rho GTPase signaling in cancer immunotherapy.","authors":"Mingjun Cai, Fukun Guo, Yi Zheng","doi":"10.1042/BST20260485","DOIUrl":"10.1042/BST20260485","url":null,"abstract":"Cancer immunotherapy, including immune checkpoint inhibitors (ICIs) and chimera-antigen receptor (CAR)-T cell therapy, has achieved substantial clinical success. However, response rates remain limited in many patients due to tumor-intrinsic immune evasion and immune cell dysfunction within the tumor microenvironment (TME). Rho family small GTPases are key signaling regulators of cytoskeletal dynamics, intracellular trafficking, transcription, and metabolism in cancers. Emerging evidence implicates Rho GTPase signaling in mediating immunotherapy efficiency through its context-dependent functions. Individual Rho GTPases modulate immunotherapy responses in tumor cells and various immune cells through actomyosin-mediated chemotaxis, cell junctions, cell polarity, and gene/epigenetic networks, among other pathways. The present review summarizes both the direct evidence linking Rho GTPases in tumor cells to immunotherapy responses and the indirect role of the selective Rho GTPase signaling network in various immune cells, with a focus on the recent progress in understanding the molecular mechanisms and associated outcomes of the ICIs and CAR-T cell therapies. We highlight current knowledge gaps at the intersection of Rho GTPase biology and cancer immunology and discuss therapeutic implications, proposing that selective modulation of specific Rho GTPase signaling pathways in tumor or TME immune cells represents a promising strategy to improve immunotherapy efficiency.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 7","pages":"815-829"},"PeriodicalIF":4.4,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13305818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306778","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

Mechanisms influencing transient cytoplasmic protein targeting to intracellular lipid droplets. 影响瞬时胞质蛋白靶向胞内脂滴的机制。

IF 4.4 3区生物学

Biochemical Society transactions Pub Date : 2026-07-29 DOI: 10.1042/BST20250461

Jay L Laws, Ebony A Monson, Lachlan A Wallace, Karla J Helbig, Cameron J Reddington

引用次数: 0

Nitroxoline revisited: antibacterial mechanisms, spectrum, and therapeutic potential of an old drug in the era of antimicrobial resistance. 硝基喹啉重访：抗菌机制，频谱，和治疗潜力的一个老药在抗菌素耐药性的时代。

IF 4.4 3区生物学

Biochemical Society transactions Pub Date : 2026-07-29 DOI: 10.1042/BST20250045

Elisabetta Cacace, Stephan Göttig

{"title":"Nitroxoline revisited: antibacterial mechanisms, spectrum, and therapeutic potential of an old drug in the era of antimicrobial resistance.","authors":"Elisabetta Cacace, Stephan Göttig","doi":"10.1042/BST20250045","DOIUrl":"10.1042/BST20250045","url":null,"abstract":"As the spread of antimicrobial resistance outpaces antibiotic discovery and marketing, there is a critical need to revisit approved compounds with untapped potential. Metal-based complexes (metallo-antimicrobials) represent ideal candidates for such efforts due to their pleiotropic effects, which, unlike antibiotics with single protein targets, may have lower resistance potential. With its well-characterised safety profile, nitroxoline, an 8-hydroxyquinoline derivative, is a prominent compound of this kind. Here, we review recent advances in our understanding of nitroxoline's multimodal mode of action, focusing on its disruption of metal homeostasis at the intracellular and extracellular level. We further explore its clinical utility, including its low propensity for resistance development, and its potential for both combinatorial therapy and as an anti-biofilm agent. Although beyond the scope of the present review, we refer to nitroxoline's antifungal effects whenever they represent a relevant comparison with its antibacterial activity. We highlight current knowledge gaps in nitroxoline's mechanism and in vivo activity that should be bridged to accelerate its repurposing, particularly in the treatment of multidrug-resistant and biofilm-associated infections. Several recent reviews have examined nitroxoline from chemical, clinical, and repurposing perspectives [1, 2, 3, 4]. The present work complements these by providing a mechanistic synthesis of nitroxoline's effects in bacteria, linking its multimodal mode of action to the knowledge gaps that should be addressed before clinical repurposing can proceed.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 7","pages":"937-947"},"PeriodicalIF":4.4,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13358727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410071","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

Bottom-up reconstitution of model membrane systems: a mini-review. 模型膜系统的自下而上重构：一个小回顾。

IF 4.4 3区生物学

Biochemical Society transactions Pub Date : 2026-07-29 DOI: 10.1042/BST20250291

Hemraj Meena, Katon Wibowo, Nicola De Franceschi

引用次数: 0

Advancing the monitoring of organelle contact sites in vitro and in vivo. 推进细胞器接触部位的体外和体内监测。

IF 4.4 3区生物学

Biochemical Society transactions Pub Date : 2026-07-29 DOI: 10.1042/BST20250371

Lucia Barazzuol, Caterina Peggion, Marisa Brini, Yusuke Nasu, Tito Calì

{"title":"Advancing the monitoring of organelle contact sites in vitro and in vivo.","authors":"Lucia Barazzuol, Caterina Peggion, Marisa Brini, Yusuke Nasu, Tito Calì","doi":"10.1042/BST20250371","DOIUrl":"10.1042/BST20250371","url":null,"abstract":"Organelle contact sites are highly dynamic and specialized regions where distinct organelles come into proximity, enabling direct inter-organelle communication. These structures play fundamental roles in cellular homeostasis by coordinating the exchange of lipids, metabolites, and ions, as well as regulating key processes such as organelle dynamics, mitochondrial fission, autophagy, and metabolic integration. Alterations in contact site architecture and function have been increasingly associated with a wide range of human diseases, including neurodegeneration, metabolic disorders, and cancer. Despite their biological relevance, the nanoscale nature and dynamic behaviour of contact sites have historically posed significant challenges for their accurate detection and functional characterization. Here, we provide a comprehensive overview of the methodologies currently available to study organelle contact sites, ranging from classical approaches such as electron microscopy and biochemical fractionation to advanced imaging techniques and genetically encoded reporters. We discuss recent developments in high-resolution and live-cell microscopy that have improved the spatial and temporal resolution of contact site analysis, as well as emerging tools designed to selectively label, quantify, and manipulate these interfaces. Attention is given to the next generation of engineered reporters capable of sensing molecular and ionic exchanges at contact sites, thereby moving beyond structural description toward functional interrogation. By critically evaluating the strengths and limitations of existing approaches, we aim to provide a framework for selecting appropriate tools and to highlight future directions in the field. Ultimately, advancing our ability to monitor and dissect organelle contact sites will be essential for understanding their contribution to cellular physiology and disease.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 7","pages":"887-899"},"PeriodicalIF":4.4,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13314530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343867","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

Theme and variations: activation and regulation of gasdermin-mediated inflammation. 主题和变化：激活和调节气凝胶介导的炎症。

IF 4.4 3区生物学

Biochemical Society transactions Pub Date : 2026-07-29 DOI: 10.1042/BST20250185

Eleanor Yeats Rothera, Soyar Horam, Yizeng Hu, Szu-An Lin, Aidan J David, Tsan Sam Xiao

{"title":"Theme and variations: activation and regulation of gasdermin-mediated inflammation.","authors":"Eleanor Yeats Rothera, Soyar Horam, Yizeng Hu, Szu-An Lin, Aidan J David, Tsan Sam Xiao","doi":"10.1042/BST20250185","DOIUrl":"10.1042/BST20250185","url":null,"abstract":"Gasdermins are effectors for pyroptosis, a highly inflammatory form of cell death. Mammalian gasdermin (GSDM) family members harbor N-terminal domains (NTDs) that bind membrane phospholipids and assemble oligomeric pores. Their C-terminal domains are regulatory modules, which suppress the cytolytic function of the NTDs under homeostatic conditions, and in several cases mediate the recruitment of proteases that cleave GSDMs following upstream signaling. The initial model for gasdermin activation was that upon protease processing their NTDs localize to the plasma membrane to assemble oligomeric pores and mediate pyroptosis. Emerging evidence suggests fascinating variations of this paradigm. For example, cleavage-independent pyroptotic activities have been reported for several family members that undergo post-translational modifications such as S-acylation, PARylation, oxidation, or phosphorylation. Furthermore, some gasdermins associate with membranes from organelles such as mitochondria, and often play non-pyroptotic roles in cellular physiology. In the present mini-review, we briefly summarize the molecular mechanisms governing the activation of different gasdermin family members, focusing on protease processing as the most well-studied mechanism. This is followed by discussion of two aspects of gasdermin biology. Namely, cleavage-independent pyroptotic activities and the localization of gasdermins at mitochondria and nucleus implicated in pyroptotic and non-pyroptotic functions. The diverse mechanisms of gasdermin activation and regulation in response to different upstream signaling pathways demonstrate the versatility of this conserved family of pore-forming proteins in various aspects of cellular physiology throughout evolution. The pleiotropic functions of gasdermins in inflammatory disorders, antimicrobial defense, antitumor immunity, neurodegenerative disorders etc., suggest fertile ground for exploration of therapeutic avenues.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 7","pages":"831-843"},"PeriodicalIF":4.4,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13305819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306754","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