Biochemical Society transactions最新文献

{"title":"Regulation via compartmentation: adaptive localization of the proteasome under stress.","authors":"Aaron Ciechanover, Ido Livneh","doi":"10.1042/BST20253082","DOIUrl":"10.1042/BST20253082","url":null,"abstract":"<p><p>Protein degradation by the ubiquitin-proteasome system and autophagy are essential mechanisms that are involved in virtually all cellular activities, and their inadequate function was shown to underlie the pathogenesis of various medical conditions. Much of the study into these proteolytic systems has been focused on the components that facilitate the selective substrate identification and targeting for degradation. Given that most of the specific breakdown of proteins is mediated via their modification by ubiquitin, much research was dedicated to the enzymes which are responsible for substrate recognition and ubiquitination-E3 ubiquitin ligases. In addition to the complexity of substrate recognition and targeting for degradation, the mechanisms governing proteasome function were found to be tightly regulated, including the assembly of the different proteasomal sub-complexes, its different compositions and specialized subtypes such as the immunoproteasome, posttranslational modification of proteasomal subunits, and adaptations in its activity in face of different cellular states and stress conditions. Studies from recent years have highlighted an as-yet unexplored tier of proteasome regulation, namely its subcellular compartmentation and trafficking. Intracellular proteasome shuttling was shown to serve as an essential stress-coping mechanism in tumor cells and is emerging as a potential target for therapeutic interventions.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1469-1478"},"PeriodicalIF":4.3,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12751074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145720977","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}

{"title":"Unraveling the interplay of DNA methylation and chromosome organization.","authors":"Yuhe Pei, Guoqiang Li","doi":"10.1042/BST20253094","DOIUrl":"10.1042/BST20253094","url":null,"abstract":"<p><p>Eukaryotic DNA has been covalently modified by DNA methylation and folded into a three-dimensional conformation in the nucleus. While the functions of DNA methylation and chromosome organization have been widely discussed, respectively, the interplay between DNA methylation and chromosome organization remains less clear and needs to be further explained. In this review, we first discuss the cross-talk between DNA methylation and chromosome conformation, highlighting the complexity and importance of DNA methylation on chromosome organization. We also summarize the current methodologies that capture DNA methylation and chromosome organization individually or simultaneously in bulk and single cells. These mechanistic and methodological advancements facilitate broad interest in unveiling the interplay between DNA methylation and chromosome organization.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1433-1444"},"PeriodicalIF":4.4,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12751065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548101","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}

{"title":"Cell fusion in osteoclastogenesis.","authors":"Leonid V Chernomordik, Kamran Melikov","doi":"10.1042/BST20253131","DOIUrl":"10.1042/BST20253131","url":null,"abstract":"<p><p>Multinucleated osteoclasts, generated by fusion of mononucleated precursors, play an essential role in the lifelong remodeling of our bones. Since within the physiological range of osteoclast sizes, their bone-resorbing activity grows with successive fusion events, both initiation of this fusion reaction and its switch off are tightly controlled. In this review, we discuss the mechanisms and proteins that facilitate and regulate this fusion process. The pathway of membrane rearrangements in osteoclast fusion shares many mechanistic motifs with other physiologically important cell-cell fusion processes, such as the formation of multinucleated skeletal muscle cells. However, the protein machinery involved in catalyzing these rearrangements in osteoclasts is still poorly understood. A better understanding of the mechanism of osteoclast fusion will hopefully lead to more effective approaches for treating skeletal diseases caused by excessive or insufficient bone resorption.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1493-1505"},"PeriodicalIF":4.3,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12862956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793113","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}

{"title":"Force writes memory: proline isomerization as a molecular memory switch.","authors":"Ionel Popa, Ronen Berkovich","doi":"10.1042/BST20253127","DOIUrl":"10.1042/BST20253127","url":null,"abstract":"<p><p>Mechanical forces play a pivotal role in cellular processes, acting as molecular switches that encode, store, and retrieve information, thereby facilitating a form of molecular memory. This review explores how protein unfolding and refolding under tensile loads generate history-dependent responses that regulate domain stability and function. We focus on proline isomerization as a reversible switch, enabling distinct quasi-stable states that underpin medium- to long-term mechanical memory. Leveraging insights from molecular dynamics simulations and experimental data, we propose that proline isomerization creates a graded, adaptive memory response, distinct from binary on-off switches, with implications for biomaterial design and biorobotics. This mechanism offers a framework for developing force-responsive materials with memory properties, enhancing applications in tissue engineering and soft robotics.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12794313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145817715","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}

{"title":"Towards a phylogenetically informed approach to solving protein-protein interactions.","authors":"Chun Shen Lim, Peter Mace, Peter C Fineran, Paul P Gardner","doi":"10.1042/BST20253031","DOIUrl":"10.1042/BST20253031","url":null,"abstract":"<p><p>Protein-protein interactions (PPIs) are critical to all cellular activities. Despite having a large number of proteins, cells have spatial and temporal control over PPIs to avoid dysregulation in cellular pathways. Considerable research efforts have aimed to find new PPIs, curate PPIs from the literature and build searchable PPI databases. These databases have been widely used by experimental and computational scientists. Here we find that the PPIs captured by these databases are highly heterogeneous and concentrated on a small number of species. These issues hamper researchers from capturing the full landscape of reliable PPIs, affecting the accuracy of machine-learning models and the effectiveness of experimental designs. However, there are opportunities to fill gaps computationally and experimentally. We suggest developing a phylogenetically informed approach to test PPIs experimentally and computationally.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12751078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676352","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}

{"title":"Critical roles of plasma membrane dynamics and heterogeneity at the early stage of antigen-stimulated FcεRI signaling in mast cells.","authors":"Dishari Medda, Nirmalya Bag","doi":"10.1042/BST20253073","DOIUrl":"10.1042/BST20253073","url":null,"abstract":"<p><p>Stimulated transmembrane (TM) signaling mediated by plasma membrane localized receptors is central to numerous cellular processes, and their dysregulation leads to pathological conditions. Antigen (Ag) stimulated clustering of high-affinity immunoglobulin E (IgE) receptor FcεRI and its functional coupling of selective signaling components such as kinases, but not phosphatases, in the early stage of mast cell signaling represents the general paradigm of TM signaling mediated by membrane receptors lacking kinase module. It has been long thought that plasma membrane organizational features, especially ordered regions and cortical cytoskeletons network, play crucial roles in efficient spatial sorting of the signaling components. In this review, we highlight the observations made by advanced imaging and spectroscopy techniques at high spatial and temporal resolution that essentially establish novel principles of plasma membrane 'adaptivity' in regulating the initial steps of stimulated mast cell signaling involving Ag cross-linked IgE-FcεRI receptor.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1283-1294"},"PeriodicalIF":4.3,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12687437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249429","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}

{"title":"Ins and outs of IRES elements: function and significance.","authors":"Encarnacion Martínez-Salas","doi":"10.1042/BST20253097","DOIUrl":"10.1042/BST20253097","url":null,"abstract":"<p><p>RNA and proteins are key components of all organisms. Internal ribosome entry site (IRES) elements are a diverse type of RNA regulatory structural elements that mediate end-independent, internal translation initiation in viral mRNAs and certain cellular mRNAs translated under stress conditions. Notably, viral IRES elements regulate translation initiation via a dynamic, modular RNA structure organization, which serves as the anchoring site for the ribosome guided by RNA-RNA and/or RNA-protein interactions. The implementation of advanced transcriptomics, proteomics, and computational methodologies has facilitated the identification of novel RNAs potentially translated using cap-independent mechanisms, harboring RNA structural elements with distinctive features. Here, we present a summary of the current understanding of IRES elements, focusing on the molecular functions and the RNA-binding proteins regulating IRES activity.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1377-1386"},"PeriodicalIF":4.3,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12687423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145385290","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}

{"title":"Are you having a LaPh? Diverse roles of Labile Phosphorylation in mammalian cells.","authors":"Christopher J Clarke, Claire E Eyers","doi":"10.1042/BST20253100","DOIUrl":"10.1042/BST20253100","url":null,"abstract":"<p><p>Phosphorylation plays a central role in regulating signal transduction across all kingdoms of life, allowing organisms to sense and respond to their environment. In mammals, the signalling research field is dominated by the functions of pSer, pThr and pTyr, due to both historical and technological factors. Mostly ignored are the labile phosphosites (LaPhs), made up of six other phosphorylatable amino acids: His, Lys, Arg, Asp, Glu and Cys. This group is characterised by an acid and/or heat-labile phosphate linkage, forming a distinct group from the highly stable phosphomonoesters of pSer, pThr and pTyr. LaPhs have distinct thermal and pH stability profiles, which may contribute to, or even dictate, their functions. Here, we review the contribution of LaPhs to mammalian signalling networks, highlighting their currently defined diverse functions.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1337-1349"},"PeriodicalIF":4.3,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12687438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343084","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}

{"title":"Transcriptional condensates and the nuclear pore complex regulate gene expression and 3D genome architecture in response to stress.","authors":"Suman Mohajan, David S Gross","doi":"10.1042/BST20253086","DOIUrl":"10.1042/BST20253086","url":null,"abstract":"<p><p>Cells respond to thermal, chemical, and oxidative stress by activating an evolutionarily conserved adaptive mechanism known as the heat shock response (HSR) that maintains protein homeostasis and ensures cell survival. Central to the HSR is Heat Shock Factor 1 (HSF1), a highly conserved master transcription factor that up-regulates genes encoding molecular chaperones and other homeostasis factors in response to proteotoxic stress. In both yeast and mammals, the HSR is accompanied by the inducible formation of phase-separated condensates that concentrate components of the transcriptional machinery into discrete intranuclear foci. The assembly of these condensates may be driven by a combination of liquid-liquid phase separation and low-valency Interactions with spatially Clustered Binding Sites (ICBS). In budding yeast, these condensates - which contain HSF1, Mediator, and RNA polymerase II - drive concerted intraand interchromosomal interactions between HSF1 target genes, creating extensive DNA loops between regulatory and transcribed sequences. In this and other ways, yeast HSR genes resemble mammalian super-enhancers. Emerging evidence suggests that the nuclear pore complex (NPC) - a macromolecular assembly at the nuclear periphery that regulates protein and RNA transport across the nuclear membrane - serves as a scaffold for the formation of transcriptional condensates and maintains chromatin architecture. In yeast, nuclear basket proteins - which dynamically exchange between the NPC and nucleoplasm - contribute to the heat shock-induced intergenic clustering of HSF1 target loci, whereas essential NPC scaffold-associated proteins do not. Such gene clustering is accompanied by the formation of multiplexed HSR mRNAs that could potentially co-ordinate both mRNA export and translation. Here we review evidence that links genome architecture, transcriptional condensates, the NPC, and nuclear basket proteins and discuss potential implications for the treatment of disease.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1295-1309"},"PeriodicalIF":4.3,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12687440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298176","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}

{"title":"Regulation of neutrophil function by the extracellular matrix.","authors":"Christopher J Calo, Margaret Radke, Tanvi Patil, Laurel E Hind","doi":"10.1042/BST20253020","DOIUrl":"10.1042/BST20253020","url":null,"abstract":"<p><p>Neutrophils play a critical role in maintaining healthy tissue by acting as the first cellular responders to inflammatory challenges. Unfortunately, when this response is dysregulated, defects in neutrophil function can contribute to the pathogenesis of several diseases and conditions, including cancer, fibrosis, and aberrant wound healing. Understanding the factors that regulate the neutrophil response is critical for improving disease outcomes. It is becoming increasingly appreciated that the extracellular matrix (ECM) serves as a significant regulator of the neutrophil response. The ECM is a complex network of fibrous proteins and proteoglycans that provides both physical and biochemical cues that can modulate cell behavior. Importantly, the composition, structure, and mechanics of the ECM often undergo significant changes in disease. Studies have shown that matrix stiffness and composition can alter neutrophil behavior, but our understanding of how the various structural and mechanical properties of the ECM govern the neutrophil response remains incomplete. In part, this is due to the challenges involved in isolating distinct properties of the matrix to determine their individual roles in regulating the neutrophil response. In this review, we summarize the recent efforts that have been made to better understand how ECM properties affect the neutrophil inflammatory response and offer suggestions for future directions for the field.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1325-1336"},"PeriodicalIF":4.3,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12687429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306701","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}