Biochemical Society transactions最新文献_第3页

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

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

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

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

Understanding the release mechanisms and secretion patterns for glucagon-like peptide-1 using the isolated perfused intestine as a model.

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-01-31 DOI: 10.1042/BST20241062

Katrine D Galsgaard, Ida M Modvig, Jens J Holst

{"title":"Understanding the release mechanisms and secretion patterns for glucagon-like peptide-1 using the isolated perfused intestine as a model.","authors":"Katrine D Galsgaard, Ida M Modvig, Jens J Holst","doi":"10.1042/BST20241062","DOIUrl":"https://doi.org/10.1042/BST20241062","url":null,"abstract":"In the gastrointestinal (GI) tract, food is digested and absorbed while GI hormones are secreted from the enteroendocrine cells (EECs). These hormones regulate food intake, glucose homeostasis, digestion, GI motility, and metabolism. Although ECCs may express more than a single hormone, the ECCs usually secrete only one or a few hormones. The pattern of EEC secretion varies along the length of the GI tract as the different EEC types are scattered in different densities along the GI tract. Following bariatric surgery, a postprandial hypersecretion of certain GI hormones occurs which contributes to the postsurgery weight loss. Mimicking this postprandial hypersecretion of GI hormones by targeting endogenous EEC secretion, using specific modulators of receptors, ion channels, and transporters found on specific EECs, to induce weight loss is a current research aim. To achieve this, a more complete understanding of the release mechanisms, expression of receptors, transporters, and the secretion pattern of the different ECC types is needed. Using the vascularly perfused intestinal model, it is possible to obtain a detailed knowledge of these release mechanisms by evaluating the effects on secretion of blocking or stimulating specific receptors, ion channels, and transporters as well as evaluating nutrient handling and absorption in each of the different sections of the intestine. This mini-review will focus on how the isolated perfused intestine has been used in our group as a model to investigate the nutrient-induced release mechanisms of ECCs with a focus on glucagon-like peptide-1 secreting cells.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063319","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

Axonemal microtubule dynamics in the assembly and disassembly of cilia.

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-01-31 DOI: 10.1042/BST20240688

Yi Zhang, Mu He, Junmin Pan

引用次数: 0

Structural glycobiology - from enzymes to organelles.

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-01-31 DOI: 10.1042/BST20241119

Courtney J Mycroft-West, Miron A Leanca, Liang Wu

{"title":"Structural glycobiology - from enzymes to organelles.","authors":"Courtney J Mycroft-West, Miron A Leanca, Liang Wu","doi":"10.1042/BST20241119","DOIUrl":"https://doi.org/10.1042/BST20241119","url":null,"abstract":"Biological carbohydrate polymers represent some of the most complex molecules in life, enabling their participation in a huge range of physiological functions. The complexity of biological carbohydrates arises from an extensive enzymatic repertoire involved in their construction, deconstruction and modification. Over the past decades, structural studies of carbohydrate processing enzymes have driven major insights into their mechanisms, supporting associated applications across medicine and biotechnology. Despite these successes, our understanding of how multienzyme networks function to create complex polysaccharides is still limited. Emerging techniques such as super-resolution microscopy and cryo-electron tomography are now enabling the investigation of native biological systems at near molecular resolutions. Here, we review insights from classical in vitro studies of carbohydrate processing, alongside recent in situ studies of glycosylation-related processes. While considerable technical challenges remain, the integration of molecular mechanisms with true biological context promises to transform our understanding of carbohydrate regulation, shining light upon the processes driving functional complexity in these essential biomolecules.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070886","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

Beyond the mono-nucleosome.

IF 3.8 3区生物学

Biochemical Society transactions Pub Date : 2025-01-31 DOI: 10.1042/BST20230721

Juliana Kikumoto Dias, Sheena D'Arcy

{"title":"Beyond the mono-nucleosome.","authors":"Juliana Kikumoto Dias, Sheena D'Arcy","doi":"10.1042/BST20230721","DOIUrl":"https://doi.org/10.1042/BST20230721","url":null,"abstract":"Nucleosomes, the building block of chromatin, are responsible for regulating access to the DNA sequence. This control is critical for essential cellular processes, including transcription and DNA replication and repair. Studying chromatin can be challenging both in vitro and in vivo, leading many to use a mono-nucleosome system to answer fundamental questions relating to chromatin regulators and binding partners. However, the mono-nucleosome fails to capture essential features of the chromatin structure, such as higher-order chromatin folding, local nucleosome-nucleosome interactions, and linker DNA trajectory and flexibility. We briefly review significant discoveries enabled by the mono-nucleosome and emphasize the need to go beyond this model system in vitro. Di-, tri-, and tetra-nucleosome arrays can answer important questions about chromatin folding, function, and dynamics. These multi-nucleosome arrays have highlighted the effects of varying linker DNA lengths, binding partners, and histone post-translational modifications in a more chromatin-like environment. We identify various chromatin regulatory mechanisms yet to be explored with multi-nucleosome arrays. Combined with in-solution biophysical techniques, studies of minimal multi-nucleosome chromatin models are feasible.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063316","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