Biochemical Society transactions最新文献

PROTACs in cancer immunotherapy: a minireview. PROTACs在癌症免疫治疗中的应用综述。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-10-01 DOI: 10.1042/BST20253065

Köckenberger J E, Cardenas Alcoser E S, Chang E T, Gutkind J S, Ferguson F M

引用次数: 0

Move over endosymbionts, peroxisomes pass electrons too. 越过内共生体，过氧化物酶体也传递电子。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-09-30 DOI: 10.1042/BST20253101

Berkley J Walker, Edward N Smith, Lee J Sweetlove

{"title":"Move over endosymbionts, peroxisomes pass electrons too.","authors":"Berkley J Walker, Edward N Smith, Lee J Sweetlove","doi":"10.1042/BST20253101","DOIUrl":"https://doi.org/10.1042/BST20253101","url":null,"abstract":"The importance of the peroxisome as a site of oxidative metabolism in plants is well recognised, but the consequences of peroxisomal biochemistry for the broader metabolic network of plant cells are somewhat overlooked. In this review, we place a spotlight on the peroxisome as a redox-active organelle which mediates substantial flows of electrons. These electron flows not only have consequences within the peroxisome, but they also flow to and from the cytosol and at least two other major redox-active organelles, chloroplasts and mitochondria, with broad implications for metabolism and redox balance of electron carriers such as NADPH and NADH. We will outline the nature of these peroxisome-mediated electron flows and discuss the new appreciation of their quantitative significance derived from metabolic network flux analysis. We emphasise that the flows of reducing equivalents into and out of the peroxisome can be substantial - in some tissues equivalent to that to and from mitochondria. We also highlight key areas of uncertainty around specific redox reactions in the peroxisome and open questions about how redox state is balanced. Finally, we also consider the implications of peroxisomal electron flows in the context of re-engineering key metabolic processes such as photorespiration and lipid accumulation.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197942","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

New molecular targets in acute leukemias: cytoskeletal regulatory proteins. 急性白血病的新分子靶点：细胞骨架调节蛋白。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-09-22 DOI: 10.1042/BST20253017

João Agostinho Machado-Neto, Hugo Passos Vicari, Jean Carlos Lipreri da Silva, Keli Lima, James Murphy

{"title":"New molecular targets in acute leukemias: cytoskeletal regulatory proteins.","authors":"João Agostinho Machado-Neto, Hugo Passos Vicari, Jean Carlos Lipreri da Silva, Keli Lima, James Murphy","doi":"10.1042/BST20253017","DOIUrl":"https://doi.org/10.1042/BST20253017","url":null,"abstract":"Acute leukemias are hematological malignancies characterized by the uncontrolled proliferation of immature bone marrow cells, disrupting normal hematopoiesis. These diseases, classified into acute lymphoblastic leukemia and acute myeloid leukemia (AML), often result from acquired genetic alterations that drive deregulated cell growth and inhibit differentiation. The cytoskeleton has emerged as a promising therapeutic target due to its pivotal role in cellular processes such as adhesion, motility, and division. Among its components, stathmin 1 (STMN1) and ezrin (EZR) stand out for their significant involvement in the pathogenesis and progression of acute leukemias. STMN1, a regulator of microtubule dynamics, is associated with chromosomal instability and leukemic cell proliferation, and is frequently overexpressed in these malignancies. Anti-microtubule agents, such as paclitaxel, eribulin, and cyclopenta[b]indole derivatives have demonstrated the ability to inhibit STMN1 by inducing its phosphorylation at regulatory sites, thereby impairing cell viability and promoting apoptosis. EZR, a membrane-actin linker protein, plays a critical role in cell signaling and tumor survival. Its overexpression has been correlated with poor prognosis in AML. Pharmacological inhibitors like NSC305787 have shown efficacy in reducing cell viability, modulating key pathways such as PI3K (phosphatidylinositol-3-kinase)/AKT (AKT serine-threonine protein)/mTOR (mammalian target of rapamycin), and enhancing the activity of standard chemotherapeutics, thereby supporting their potential use in combination therapies. This review aims to explore the roles of STMN1 and EZR in the pathogenesis of acute leukemias, assessing their potential as therapeutic targets. The goal is to synthesize recent evidence to guide the development of more effective inhibitors, focusing on overcoming therapeutic resistance and tailoring treatments to individual profiles.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124079","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 underpinning natural variation in non-photochemical quenching kinetics. 非光化学猝灭动力学中自然变化的机制。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-09-18 DOI: 10.1042/BST20253087

Katarzyna Glowacka

{"title":"Mechanisms underpinning natural variation in non-photochemical quenching kinetics.","authors":"Katarzyna Glowacka","doi":"10.1042/BST20253087","DOIUrl":"https://doi.org/10.1042/BST20253087","url":null,"abstract":"Plants use light as an energy source to reduce carbon dioxide into carbohydrates during photosynthesis. However, when the incident light exceeds the photosynthesis rate, the excess energy must be dispersed, or it can result in the unregulated formation of harmful reactive oxygen species, especially in plants exposed to very high light or abiotic stress conditions that compromise photosynthetic efficiency. The excess energy is typically dispersed harmlessly as heat, which can be measured as non-photochemical quenching (NPQ) of chlorophyll fluorescence. NPQ kinetics vary within plant populations, and understanding the basis of this variation will contribute to improving resiliency to abiotic stresses, including high light, in crops. Here it is reviewed how three key NPQ genes, Photosystem II subunit S (PsbS), Violaxanthin de-epoxidase (VDE), and Zeaxanthin epoxidase (ZEP), contribute to natural variation in NPQ kinetics. PsbS expression level is an important determinant of NPQ variation, whereas VDE and ZEP contribute to NPQ variation via post-translational regulation related to natural variation in many genes affecting these enzymes' activity. Post-translational mechanisms that influence NPQ, including redox regulation via thioredoxins and regulation of ascorbate availability, thylakoid lumen pH, and violaxanthin accessibility are discussed. There are also addressed NPQ regulatory mechanisms beyond PsbS, ZEP, and VDE, including natural regulation of light accessibility, modulation of light harvesting, and feedback from the steps following light harvesting. Finally, how this knowledge can be harnessed to engineer more resilient crops is briefly summarized.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085098","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

The impact of ribosome association on lncRNA stability: a new layer of post-transcriptional control? 核糖体结合对lncRNA稳定性的影响：转录后控制的新层面？

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-09-12 DOI: 10.1042/BST20253024

Courteney K Pienaar, Benjamin P Towler, Sarah F Newbury

{"title":"The impact of ribosome association on lncRNA stability: a new layer of post-transcriptional control?","authors":"Courteney K Pienaar, Benjamin P Towler, Sarah F Newbury","doi":"10.1042/BST20253024","DOIUrl":"https://doi.org/10.1042/BST20253024","url":null,"abstract":"Long non-coding RNAs (lncRNAs) play crucial roles in cellular processes; however, the mechanisms controlling their stability are not well understood. Since the appropriate levels of lncRNAs in cells are required to carry out their functions, it is critical that their degradation is tightly controlled. Extensive research has shown that translation and degradation of messenger RNAs (mRNAs) are intricately linked, with repression of translation usually leading to degradation of the RNA. Recently, evidence has emerged to suggest that translation may also affect lncRNA stability. Ribosome engagement may stabilise lncRNAs by protecting them from nucleases or by promoting their degradation via ribosome-associated decay pathways such as nonsense-mediated decay. In this review, we first highlight specific human diseases that result from misregulation of lncRNA stability. We then explore the mechanisms underlying ribosome association and lncRNA stability, drawing comparisons with canonical mRNA mechanisms and highlighting emerging hypotheses that may be particularly relevant to lncRNAs. We also discuss how advanced techniques such as ribosome profiling can be applied to investigate whether lncRNAs are translated. Finally, we suggest future strategies to aid further understanding of lncRNA stability and its relationship with development and disease. Understanding the dynamic relationship between translation and lncRNA decay offers broad implications for RNA biology and provides new insights into the regulation of lncRNAs in both cellular and disease contexts.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051749","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

The regulatory mechanisms controlling meiotic cross-over patterning in plants. 植物减数分裂交叉模式的调控机制。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-09-12 DOI: 10.1042/BST20253025

Wanyue Xu, Qichao Lian, Meiling Li, Gregory P Copenhaver, Yingxiang Wang

引用次数: 0

Structural and evolutionary insights into understudied bacterial serine-threonine pseudokinase families. 未被充分研究的细菌丝氨酸-苏氨酸假激酶家族的结构和进化见解。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-09-11 DOI: 10.1042/BST20253080

Brady O'Boyle, Debarshi Ryan Bhowmik, Patrick A Eyers, Dominic P Byrne, Natarajan Kannan

{"title":"Structural and evolutionary insights into understudied bacterial serine-threonine pseudokinase families.","authors":"Brady O'Boyle, Debarshi Ryan Bhowmik, Patrick A Eyers, Dominic P Byrne, Natarajan Kannan","doi":"10.1042/BST20253080","DOIUrl":"https://doi.org/10.1042/BST20253080","url":null,"abstract":"Pseudokinases, once considered catalytically inactive remnants of evolution, have emerged as key regulators of numerous fundamental biological processes. While eukaryotic pseudokinases have attracted significant attention, bacterial pseudokinases remain largely unexplored experimentally. Recent advances in sequence analysis and structural modeling have identified and characterized multiple conserved bacterial pseudokinase families, each with distinct predicted catalytic impairments but unknown functions. This review delves into their classification, structural features, and evolutionary adaptation. We also highlight the significance of bacterial pseudokinases in host-microbe interactions and their emerging potential as therapeutic targets. By integrating bioinformatics with experimental approaches, future research is poised to uncover the biological functions of bacterial pseudokinases, providing new insights into microbial signaling mechanisms and revealing new strategies to interrogate bacterial cell signaling, including pseudokinase drivers of infection and antimicrobial drug resistance.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051688","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

Mechanistic insights into MET exon 14 skipping mutations and their role in tumor progression. MET外显子14跳过突变的机制及其在肿瘤进展中的作用。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-09-09 DOI: 10.1042/BST20253091

Promita Ghosh, Isabella Pecora, Morag Park

{"title":"Mechanistic insights into MET exon 14 skipping mutations and their role in tumor progression.","authors":"Promita Ghosh, Isabella Pecora, Morag Park","doi":"10.1042/BST20253091","DOIUrl":"https://doi.org/10.1042/BST20253091","url":null,"abstract":"The MET receptor tyrosine kinase is a pivotal regulator of cellular survival, motility, and proliferation. Mutations leading to skipping of exon 14 (METΔex14) within the juxtamembrane domain of MET impair receptor degradation and prolong oncogenic signaling, contributing significantly to tumor progression across multiple cancer types. METΔex14 mutations are associated with aggressive clinical behavior, therapeutic resistance, and poor outcomes. Next-generation sequencing from both tissue and liquid biopsies has significantly improved the detection frequency of METΔex14 in lung and other cancers. However, clinical trials targeting METΔex14 have rendered partial responses and mixed outcomes due to the lack of a comprehensive mechanistic understanding of METΔex14 regulation and a diverse mutational landscape. This review synthesizes current knowledge on the mechanistic basis of METΔex14-driven oncogenesis, including alterations in receptor dynamics, downstream signaling perturbations, genomic alterations underlying this mutation, and mechanisms of acquired therapeutic resistance. We further discuss the clinical implications of these insights and highlight future research directions essential for optimizing targeted therapies.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028845","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 from deep mutational scanning in the context of an emerging pathogen. 在一种新出现的病原体的背景下，从深度突变扫描的见解。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-09-04 DOI: 10.1042/BST20253033

Melissa J Call, Matthew E Call, Xinyu Wu

引用次数: 0

Using modified mRNA for cardiomyocyte proliferation and cardiac genetic disease modelling and treatment. 利用修饰的mRNA进行心肌细胞增殖和心脏遗传疾病的建模和治疗。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-09-04 DOI: 10.1042/BST20243001

Christopher A P Batho, James E Hudson, Catherine H Wilson

{"title":"Using modified mRNA for cardiomyocyte proliferation and cardiac genetic disease modelling and treatment.","authors":"Christopher A P Batho, James E Hudson, Catherine H Wilson","doi":"10.1042/BST20243001","DOIUrl":"https://doi.org/10.1042/BST20243001","url":null,"abstract":"Heart failure (HF) is a leading cause of death worldwide and the associated mortality and socioeconomic burden is predicted to worsen. Current therapies for HF focus on managing the causes and symptoms; however, these current treatment options are unable to reverse heart muscle degeneration, with heart transplantation the only cure. The ability to re-muscularise the heart represents a significant unmet clinical need. Although numerous biological pathways driving re-muscularisation have been identified, delivery of therapeutic factors is challenging. Modified mRNA (modRNA) is synthetic mRNA with greater gene packaging capacity, low immunogenic response and allows transient but robust protein expression. In this mini-review, we highlight the emerging discoveries surrounding the application of modRNA in the cardiovascular field. Specifically, we focus on different examples illustrating how modRNA delivery post-myocardial infarction can drive cardiomyocyte proliferation and achieve cardiac regeneration. In addition, we demonstrate how modRNA is being used for protein replacement and Cas delivery for both modelling and therapeutic studies focussed on genetic cardiac diseases. For these applications, in particular Cas delivery, the transient nature of modRNA overexpression is a beneficial property with reduced side effects compared with other modalities. Finally, we preview some of the roadblocks limiting the clinical translation of modRNA and avenues being explored to overcome these. In summary, the flexibility of modRNA combined with its improved safety profile provides a gene overexpression tool capable of integration into all steps of the preclinical and clinical therapeutic pipeline enabling the discovery of improved treatments for HF.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991428","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