Biochemical Society transactions最新文献

Small RNA-mediated suppression of sex chromosome meiotic conflicts during Drosophila male gametogenesis.

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-02-06 DOI: 10.1042/BST20240344

Jeffrey Vedanayagam

引用次数: 0

The role of transcription bodies in gene expression: what embryos teach us.

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-02-06 DOI: 10.1042/BST20240599

Martino Ugolini, Nadine L Vastenhouw

{"title":"The role of transcription bodies in gene expression: what embryos teach us.","authors":"Martino Ugolini, Nadine L Vastenhouw","doi":"10.1042/BST20240599","DOIUrl":"https://doi.org/10.1042/BST20240599","url":null,"abstract":"Transcription does not occur diffusely throughout the nucleus but is concentrated in specific areas. Areas of accumulated transcriptional machinery have been called clusters, hubs, or condensates, while transcriptionally active areas have been referred to as transcription factories or transcription bodies. Despite the widespread occurrence of transcription bodies, it has been difficult to study their assembly, function, and effect on gene expression. This review highlights the advantages of developmental model systems such as zebrafish and fruit fly embryos, in addressing these questions. We focus on three important discoveries that were made in embryos. (i) It had previously been suggested that, in transcription bodies, the different steps of the transcription process are organized in space. We explore how work in embryos has revealed that they can also be organized in time. In this case, transcription bodies mature from transcription factor clusters to elongating transcription bodies. This type of organization has important implications for transcription body function. (ii) The relevance of clustering for in vivo gene regulation has benefited greatly from studies in embryos. We discuss examples in which transcription bodies regulate developmental gene expression by compensating for low transcription factor concentrations and low-affinity enhancers. Finally, (iii) while accumulations of transcriptional machinery can facilitate transcription locally, work in embryos showed that transcription bodies can also sequester the transcriptional machinery, modulating the availability for activity at other sites. In brief, the reviewed literature highlights the properties of developmental model organisms that make them powerful systems for uncovering the form and function of transcription bodies.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254545","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

Electrosome assembly: Structural insights from high voltage-activated calcium channel (CaV)-chaperone interactions.

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-02-06 DOI: 10.1042/BST20240422

Zhou Chen, Daniel L Minor

{"title":"Electrosome assembly: Structural insights from high voltage-activated calcium channel (CaV)-chaperone interactions.","authors":"Zhou Chen, Daniel L Minor","doi":"10.1042/BST20240422","DOIUrl":"https://doi.org/10.1042/BST20240422","url":null,"abstract":"Ion channels are multicomponent complexes (termed here as\"electrosomes\") that conduct the bioelectrical signals required for life. It has been appreciated for decades that assembly is critical for proper channel function, but knowledge of the factors that undergird this important process has been lacking. Although there are now exemplar structures of representatives of most major ion channel classes, there has been no direct structural information to inform how these complicated, multipart complexes are put together or whether they interact with chaperone proteins that aid in their assembly. Recent structural characterization of a complex of the endoplasmic membrane protein complex (EMC) chaperone and a voltage-gated calcium channel (CaV) assembly intermediate comprising the pore-forming CaVα1 and cytoplasmic CaVβ subunits offers the first structural view into the assembly of a member of the largest ion channel class, the voltagegated ion channel (VGIC) superfamily. The structure shows how the EMC remodels the CaVα1/CaVβ complex through a set of rigid body movements for handoff to the extracellular CaVα2δ subunit to complete channel assembly in a process that involves intersubunit coordination of a divalent cation and ordering of CaVα1 elements. These findings set a new framework for deciphering the structural underpinnings of ion channel biogenesis that has implications for understanding channel function, how drugs and disease mutations act, and for investigating how other membrane proteins may engage the ubiquitous EMC chaperone.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254488","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

Same same but different? How blood and lymphatic vessels induce cell contact inhibition.

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-02-06 DOI: 10.1042/BST20240573

Claudia Carlantoni, Leon M H Liekfeld, Manu Beerens, Maike Frye

{"title":"Same same but different? How blood and lymphatic vessels induce cell contact inhibition.","authors":"Claudia Carlantoni, Leon M H Liekfeld, Manu Beerens, Maike Frye","doi":"10.1042/BST20240573","DOIUrl":"https://doi.org/10.1042/BST20240573","url":null,"abstract":"Endothelial cells (ECs) migrate, sprout, and proliferate in response to (lymph)angiogenic mitogens, such as vascular endothelial growth factors. When ECs reach high confluency and encounter spatial confinement, they establish mature cell-cell junctions, reduce proliferation, and enter a quiescent state through a process known as contact inhibition. However, EC quiescence is modulated not only by spatial confinement but also by other mechano-environmental factors, including blood or lymph flow and extracellular matrix properties. Changes in physical forces and intracellular signaling can disrupt contact inhibition, resulting in aberrant proliferation and vascular dysfunction. Therefore, it is critical to understand the mechanisms by which endothelial cells regulate contact inhibition. While contact inhibition has been well studied in blood endothelial cells (BECs), its regulation in lymphatic endothelial cells (LECs) remains largely unexplored. Here, we review the current knowledge on extrinsic stimuli and intrinsic molecular pathways that govern endothelial contact inhibition and highlight nuanced differences between BECs and LECs. Furthermore, we provide perspectives for future research on lymphatic contact inhibition. A deeper understanding of the BEC and LEC-specific pathways underlying contact inhibition may enable targeted modulation of this process in blood or lymphatic vessels with relevance to lymphatic or blood vascular-specific disorders.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254491","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

Exploring the oncogenic roles of T-box transcription factor TBX2 and its potential as a therapeutic target.

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-02-06 DOI: 10.1042/BST20241069

Claire Bellis, Mihlali V Mlaza, Abid Ali, Amaal Abrahams, Sharon Prince

{"title":"Exploring the oncogenic roles of T-box transcription factor TBX2 and its potential as a therapeutic target.","authors":"Claire Bellis, Mihlali V Mlaza, Abid Ali, Amaal Abrahams, Sharon Prince","doi":"10.1042/BST20241069","DOIUrl":"https://doi.org/10.1042/BST20241069","url":null,"abstract":"During embryonic development, the T-box transcription factor TBX2 regulates key processes such as cell fate decisions, migration and tissue morphogenesis, and mutations that lead to reduced TBX2 levels result in developmental abnormalities including congenital heart and skeletal defects. TBX2, on the other hand, is overexpressed in a plethora of cancers where it functions as a powerful oncogene contributing to processes ranging from the bypass of senescence and cell death pathways to the promotion of cell proliferation, and epithelial-to-mesenchymal transition to drive invasion and metastasis. Additionally, TBX2 has been implicated in conferring resistance to anti-cancer drugs resulting in poor therapeutic outcomes. To exert its oncogenic functions, TBX2 transcriptionally represses key tumour suppressor genes involved in controlling cell proliferation and epithelial-to-mesenchymal transition such as p21Cip1, p14/p19ARF PTEN, NDRG1, CST6 and E-cadherin. This repression has been shown to involve complex mechanisms by which TBX2 co-opts transcription factors and recruits co-repression complexes to the promoters of these tumour suppressor genes. While limited information is available on how TBX2 is regulated in cancers, there is evidence that the levels and oncogenic functions of TBX2 are induced by developmental signalling pathways that are hijacked by cancer cells such as the Wnt/β-catenin and PI3K/AKT pathways. Understanding the complex molecular networks that TBX2 is involved in to exert its oncogenic functions is important because it may reveal potential therapeutic strategies for targeting TBX2 in TBX2-dependent cancers. This minireview discusses TBX2's involvement in cancer signalling, its regulatory partners, and its impact on cancer progression and resistance to therapy.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254490","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

Activation is only the beginning: mechanisms that tune kinase substrate specificity.

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-02-05 DOI: 10.1042/BST20241420

Landon K Clark, Sierra N Cullati

{"title":"Activation is only the beginning: mechanisms that tune kinase substrate specificity.","authors":"Landon K Clark, Sierra N Cullati","doi":"10.1042/BST20241420","DOIUrl":"https://doi.org/10.1042/BST20241420","url":null,"abstract":"Kinases are master coordinators of cellular processes, but to appropriately respond to the changing cellular environment, each kinase must recognize its substrates, target only those proteins on the correct amino acids, and in many cases, only phosphorylate a subset of potential substrates at any given time. Therefore, regulation of kinase substrate specificity is paramount to proper cellular function, and multiple mechanisms can be employed to achieve specificity. At the smallest scale, characteristics of the substrate such as its linear peptide motif and three-dimensional structure must be complementary to the substrate binding surface of the kinase. This surface is dynamically shaped by the activation loop and surrounding region of the substrate binding groove, which can adopt multiple conformations, often influenced by post-translational modifications. Domain-scale conformational changes can also occur, such as the interaction with pseudosubstrate domains or other regulatory domains in the kinase. Kinases may multimerize or form complexes with other proteins that influence their structure, function, and/or subcellular localization at different times and in response to different signals. This review will illustrate these mechanisms by examining recent work on four serine/threonine kinases: Aurora B, CaMKII, GSK3β, and CK1δ. We find that these mechanisms are often shared by this diverse set of kinases in diverse cellular contexts, so they may represent common strategies that cells use to regulate cell signaling, and it will be enlightening to continue to learn about the depth and robustness of kinase substrate specificity in additional systems.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187651","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

Current understanding of heparanase 2 regulation, a non-heparanase.

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-02-05 DOI: 10.1042/BST20241281

Yannic Becker, Hermann Haller

引用次数: 0

Structural switching of tubulin in the microtubule lattice.

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-02-05 DOI: 10.1042/BST20240360

Yean-Ming Chew, Robert A Cross

引用次数: 0

Exploring genome-transcriptome correlations in cancer.

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-02-05 DOI: 10.1042/BST20240108

Michael Ronemus, Daniel Bradford, Zachary Laster, Siran Li

引用次数: 0

Microscopy methods for the in vivo study of nanoscale nuclear organization.

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-02-03 DOI: 10.1042/BST20240629

Nidhi Rani Lokesh, Mark E Pownall

{"title":"Microscopy methods for the in vivo study of nanoscale nuclear organization.","authors":"Nidhi Rani Lokesh, Mark E Pownall","doi":"10.1042/BST20240629","DOIUrl":"https://doi.org/10.1042/BST20240629","url":null,"abstract":"Eukaryotic genomes are highly compacted within the nucleus and organized into complex 3D structures across various genomic and physical scales. Organization within the nucleus plays a key role in gene regulation, both facilitating regulatory interactions to promote transcription while also enabling the silencing of other genes. Despite the functional importance of genome organization in determining cell identity and function, investigating nuclear organization across this wide range of physical scales has been challenging. Microscopy provides the opportunity for direct visualization of nuclear structures and has pioneered key discoveries in this field. Nonetheless, visualization of nanoscale structures within the nucleus, such as nucleosomes and chromatin loops, requires super-resolution imaging to go beyond the ~220 nm diffraction limit. Here, we review recent advances in imaging technology and their promise to uncover new insights into the organization of the nucleus at the nanoscale. We discuss different imaging modalities and how they have been applied to the nucleus, with a focus on super-resolution light microscopy and its application to in vivo systems. Finally, we conclude with our perspective on how continued technical innovations in super-resolution imaging in the nucleus will advance our understanding of genome structure and function.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078549","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