Biochemical Society Transactions[JOURNAL]
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200 papers
How does the tubulin code facilitate directed cell migration?
Simoes-da-Silva MM, Barisic M
Biochem Soc Trans · 2025 Feb · PMID 39998313 · Full text
Besides being a component of the cytoskeleton that provides structural integrity to the cell, microtubules also serve as tracks for intracellular transport. As the building units of the mitotic spindle, microtubules dist...
Besides being a component of the cytoskeleton that provides structural integrity to the cell, microtubules also serve as tracks for intracellular transport. As the building units of the mitotic spindle, microtubules distribute chromosomes during cell division. By distributing organelles, vesicles, and proteins, they play a pivotal role in diverse cellular processes, including cell migration, during which they reorganize to facilitate cell polarization. Structurally, microtubules are built up of α/β-tubulin dimers, which consist of various tubulin isotypes that undergo multiple post-translational modifications (PTMs). These PTMs allow microtubules to differentiate into functional subsets, influencing the associated processes. This text explores the current understanding of the roles of tubulin PTMs in cell migration, particularly detyrosination and acetylation, and their implications in human diseases.
The cellular basis of meristem development in fern gametophytes.
Xie C, Zhang C, Liu X … +1 more , Zhou Y
Biochem Soc Trans · 2025 Feb · PMID 39945720 · Full text
The life cycle of land plants is characterized by alternating generations of sexual gametophytes and asexual sporophytes. Unlike seed plants, seed-free vascular plants, including ferns, initiate and maintain pluripotent...
The life cycle of land plants is characterized by alternating generations of sexual gametophytes and asexual sporophytes. Unlike seed plants, seed-free vascular plants, including ferns, initiate and maintain pluripotent meristems during their gametophyte phase to sustain body expansion and drive the formation of sexual organs for reproduction. This review summarizes meristem development among various fern species during the gametophyte phase, focusing on the cellular basis of meristem initiation, proliferation, and termination. We review the different types of gametophytic meristems in ferns, including apical cell (AC)-based meristems, multicellular apical meristems, and multicellular marginal meristems. We highlight both conserved and lineage-specific patterns of cell division, which are closely associated with these meristem identities and play crucial roles in shaping gametophytic morphology. Additionally, we highlight recent progress in understanding the dynamics of cell division and growth that drive meristem development, through studies that integrate confocal live imaging and computational quantitative analysis. Furthermore, we discuss the influence of environmental and genetic factors on cell division activity in fern gametophytes, including conserved transcriptional regulators that sustain meristem indeterminacy and proliferation in the model fern Ceratopteris richardii.
Lysine acetylation in cyanobacteria: emerging mechanisms and functions.
Liu X, Yang M, Ge F … +1 more , Zhao J
Biochem Soc Trans · 2025 Feb · PMID 39936403 · Full text
Cyanobacteria are ancient and abundant photosynthetic prokaryotes that play crucial roles in global carbon and nitrogen cycles. They exist in a variety of environments and have been used extensively as model organisms fo...
Cyanobacteria are ancient and abundant photosynthetic prokaryotes that play crucial roles in global carbon and nitrogen cycles. They exist in a variety of environments and have been used extensively as model organisms for studies of photosynthesis and environmental adaptation. Lysine acetylation (Kac), a widespread and evolutionarily conserved protein posttranslational modification, is reversibly catalyzed by lysine acetyltransferases (KAT) and lysine deacetylases (KDACs). Over the past decade, a growing number of acetylated proteins have been identified in cyanobacteria, and Kac is increasingly recognized as having essential roles in many cellular processes, such as photosynthesis, energy metabolism, and stress responses. Recently, cGNAT2 and CddA were identified as KAT and KDAC in the model cyanobacterium Synechococcus sp. PCC 7002, respectively. The identified Kac regulatory enzymes provide novel insight into the mechanisms that globally regulate photosynthesis in cyanobacteria and potentially other photosynthetic organisms. This review summarizes recent progress in our understanding of the functions and mechanisms of lysine acetylation in Cyanobacteria. The challenges and future perspectives in this field are also discussed.
PIEZO channels as multimodal mechanotransducers.
Lacroix JJ, Wijerathne TD
Biochem Soc Trans · 2025 Feb · PMID 39936392 · Full text
All living beings experience a wide range of endogenous and exogenous mechanical forces. The ability to detect these forces and rapidly convert them into specific biological signals is essential to a wide range of physio...
All living beings experience a wide range of endogenous and exogenous mechanical forces. The ability to detect these forces and rapidly convert them into specific biological signals is essential to a wide range of physiological processes. In vertebrates, these fundamental tasks are predominantly achieved by two related mechanosensitive ion channels called PIEZO1 and PIEZO2. PIEZO channels are thought to sense mechanical forces through flexible transmembrane blade-like domains. Structural studies indeed show that these mechanosensory domains adopt a curved conformation in a resting membrane but become flattened in a membrane under tension, promoting an open state. Yet, recent studies suggest the intriguing possibility that distinct mechanical stimuli activate PIEZO channels through discrete molecular rearrangements of these domains. In addition, biological signals downstream of PIEZO channel activation vary as a function of the mechanical stimulus and of the cellular context. These unique features could explain how PIEZOs confer cells the ability to differentially interpret a complex landscape of mechanical cues.
Progress toward a comprehensive brain protein interactome.
Dang V, Voigt B, Marcotte EM
Biochem Soc Trans · 2025 Feb · PMID 39936389 · Full text
Protein-protein interactions (PPIs) in the brain play critical roles across all aspects of the central nervous system, from synaptic transmission, glial development, myelination, to cell-to-cell communication, and more....
Protein-protein interactions (PPIs) in the brain play critical roles across all aspects of the central nervous system, from synaptic transmission, glial development, myelination, to cell-to-cell communication, and more. Understanding these interactions is crucial for deciphering neurological mechanisms and the underlying biochemical machinery affected in neurological disorders. Recently, advances in proteomics techniques have significantly enhanced our ability to study interactions among the proteins expressed in the brain. Here, we review some of the high-throughput studies characterizing brain PPIs, using affinity purification, proximity labeling, co-fractionation, and chemical cross-linking mass spectrometry methods, as well as yeast two-hybrid assays. We present the current state of the field, discuss challenges, and highlight promising future directions.
Advances in nanobody multimerization and multispecificity: from in vivo assembly to in vitro production.
Al-Seragi M, Chen Y, Duong van Hoa F
Biochem Soc Trans · 2025 Feb · PMID 39927832 · Full text
NANOBODIES® (Nbs) have emerged as valuable tools across therapeutic, diagnostic, and industrial applications owing to their small size and consequent ability to bind unique epitopes inaccessible to conventional antibodie...
NANOBODIES® (Nbs) have emerged as valuable tools across therapeutic, diagnostic, and industrial applications owing to their small size and consequent ability to bind unique epitopes inaccessible to conventional antibodies. While Nbs retrieved from immune libraries normally possess sufficient affinity and specificity for their cognate antigens in the practical use case, their multimerization will often increase functional affinity via avidity effects. Therefore, to rescue binding affinity and broaden targeting specificities, recent efforts have focused on conjugating multiple Nb clones - of identical or unique antigen cognates - together. In vivo and in vitro approaches, including flexible linkers, antibody domains, self-assembling coiled coils, chemical conjugation, and self-clustering hydrophobic sequences, have been employed to produce multivalent and multispecific Nb constructs. Examples of successful Nb multimerization are diverse, ranging from immunoassaying reagents to virus-neutralizing moieties. This review aims to recapitulate the in vivo and in vitro modalities to produce multivalent and multispecific Nbs while highlighting the applications, advantages, and drawbacks tied to each method.
Polymer models of chromatin organization in virally infected cells.
Fontana A, Tafuri F, Abraham A … +8 more , Bianco S, Esposito A, Conte M, Vercellone F, Pierno FD, Guha S, Carluccio CD, Chiariello AM
Biochem Soc Trans · 2025 Feb · PMID 39927819 · Full text
Genome architecture is closely tied to essential biological functions, yet a complete understanding of the mechanisms governing DNA folding remains a significant challenge. Theoretical models based on polymer physics hav...
Genome architecture is closely tied to essential biological functions, yet a complete understanding of the mechanisms governing DNA folding remains a significant challenge. Theoretical models based on polymer physics have been applied to decipher the complexity of chromatin architecture and uncover the physical processes shaping its structure. Importantly, recent findings suggest that certain viruses can alter the 3D organization of the host genome. In this review, we highlight recent advances in the development of polymer models used to study how chromatin 3D structure within a cell re-organizes following viral infection, with a particular emphasis on the SARS-CoV-2 virus, capable of altering genome organization of the host cell at different scales, including A/B compartments, TADs and gene-enhancer regulatory contacts.
Advancing structure modeling from cryo-EM maps with deep learning.
Li S, Terashi G, Zhang Z … +1 more , Kihara D
Biochem Soc Trans · 2025 Feb · PMID 39927816 · Full text
Cryo-electron microscopy (cryo-EM) has revolutionized structural biology by enabling the determination of biomolecular structures that are challenging to resolve using conventional methods. Interpreting a cryo-EM map req...
Cryo-electron microscopy (cryo-EM) has revolutionized structural biology by enabling the determination of biomolecular structures that are challenging to resolve using conventional methods. Interpreting a cryo-EM map requires accurate modeling of the structures of underlying biomolecules. Here, we concisely discuss the evolution and current state of automatic structure modeling from cryo-EM density maps. We classify modeling methods into two categories: de novo modeling methods from high-resolution maps (better than 5 Å) and methods that model by fitting individual structures of component proteins to maps at lower resolution (worse than 5 Å). Special attention is given to the role of deep learning in the modeling process, highlighting how AI-driven approaches are transformative in cryo-EM structure modeling. We conclude by discussing future directions in the field.
Conformational dynamics of the nuclear pore complex central channel.
Chen Y, Zhou G, Yu M
Biochem Soc Trans · 2025 Feb · PMID 39927798 · Publisher ↗
The nuclear pore complex (NPC) is a vital regulator of molecular transport between the nucleus and cytoplasm in eukaryotic cells. At the heart of the NPC's function are intrinsically disordered phenylalanineglycine-rich...
The nuclear pore complex (NPC) is a vital regulator of molecular transport between the nucleus and cytoplasm in eukaryotic cells. At the heart of the NPC's function are intrinsically disordered phenylalanineglycine-rich nucleoporins (FG-Nups), which form a dynamic permeability barrier within the central channel. This disordered nature facilitates efficient nucleocytoplasmic transport but also poses significant challenges to its characterization, especially within the nano-confined environment of the NPC. Recent advances in experimental techniques, such as cryo-electron microscopy, atomic force microscopy, fluorescence microscopy, and nuclear magnetic resonance, along with computational modeling, have illuminated the conformational flexibility of FG-Nups, which underpins their functional versatility. This review synthesizes these advancements, emphasizing how disruptions in FG-Nup behavior-caused by mutations or pathological interactions-contribute to diseases such as neurodegenerative disorders, aging-related decline, and viral infections. Despite progress, challenges persist in deciphering FG-Nup dynamics within the crowded and complex cellular environment, especially under pathological conditions. Addressing these gaps is critical for advancing therapeutic strategies targeting NPC dysfunction in disease progression.
'Where is my gap': mechanisms underpinning PARP inhibitor sensitivity in cancer.
Buckley-Benbow L, Agnarelli A, Bellelli R
Biochem Soc Trans · 2025 Feb · PMID 39927794 · Full text
The introduction of poly-ADP ribose polymerase (PARP) inhibitors (PARPi) has completely changed the treatment landscape of breast cancer susceptibility 1-2 (BRCA1-BRCA2)-mutant cancers and generated a new avenue of resea...
The introduction of poly-ADP ribose polymerase (PARP) inhibitors (PARPi) has completely changed the treatment landscape of breast cancer susceptibility 1-2 (BRCA1-BRCA2)-mutant cancers and generated a new avenue of research in the fields of DNA damage response and cancer therapy. Despite this, primary and secondary resistances to PARPi have become a challenge in the clinic, and novel therapies are urgently needed to address this problem. After two decades of research, a unifying model explaining sensitivity of cancer cells to PARPi is still missing. Here, we review the current knowledge in the field and the increasing evidence pointing to a crucial role for replicative gaps in mediating sensitization to PARPi in BRCA-mutant and 'wild-type' cancer cells. Finally, we discuss the challenges to be addressed to further improve the utilization of PARPi and tackle the emergence of resistance in the clinical context.
Small RNA-mediated suppression of sex chromosome meiotic conflicts during Drosophila male gametogenesis.
Vedanayagam J
Biochem Soc Trans · 2025 Feb · PMID 39918264 · Full text
Meiosis is an evolutionarily conserved process in eukaryotes that ensures equal segregation of alleles and chromosomes during reproduction. Although parity in allelic transmission is the norm, selfish genes such as meiot...
Meiosis is an evolutionarily conserved process in eukaryotes that ensures equal segregation of alleles and chromosomes during reproduction. Although parity in allelic transmission is the norm, selfish genes such as meiotic drivers can violate Mendel's first law of segregation. Sex chromosome drive is a form of meiotic drive that leads to unequal segregation of sex chromosomes, resulting in sex-ratio distortion and/or sterility in the offspring. Adverse fitness effects due to sex chromosome drive trigger the evolution of suppressors to restore Mendelian segregation. However, the molecular mechanisms by which suppressors emerge and counteract meiotic drive genes remain unclear. Recent studies from Drosophila have shed light on the critical roles of small RNA-mediated post-transcriptional silencing in mitigating sex chromosome meiotic conflicts. This review highlights the recruitment of two distinct small RNA pathways to combat intragenomic conflicts during male gametogenesis and seeks to reveal the impact of molecular arms races between meiotic drivers and their suppressors in shaping genome and sex chromosome evolution.
Electrosome assembly: Structural insights from high voltage-activated calcium channel (CaV)-chaperone interactions.
Chen Z, Minor DL
Biochem Soc Trans · 2025 Feb · PMID 39912874 · Full text
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...
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.
Exploring the oncogenic roles of T-box transcription factor TBX2 and its potential as a therapeutic target.
Bellis C, Mlaza MV, Ali A … +2 more , Abrahams A, Prince S
Biochem Soc Trans · 2025 Feb · PMID 39912718 · Full text
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 developm...
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.
Same same but different? How blood and lymphatic vessels induce cell contact inhibition.
Carlantoni C, Liekfeld LMH, Beerens M … +1 more , Frye M
Biochem Soc Trans · 2025 Feb · PMID 39912714 · Full text
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 esta...
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.
The role of transcription bodies in gene expression: what embryos teach us.
Ugolini M, Vastenhouw NL
Biochem Soc Trans · 2025 Feb · PMID 39912709 · Full text
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...
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.
Structural switching of tubulin in the microtubule lattice.
Chew YM, Cross RA
Biochem Soc Trans · 2025 Feb · PMID 39910801 · Full text
Microtubule (MT) dynamic instability, a cycle of growth, catastrophe, shrinkage and rescue, is driven by the switching of tubulin between two structural states, one stabilised by GTP and the other by GDP. Recent work has...
Microtubule (MT) dynamic instability, a cycle of growth, catastrophe, shrinkage and rescue, is driven by the switching of tubulin between two structural states, one stabilised by GTP and the other by GDP. Recent work has uncovered the ancient origins of this structural switch and revealed further fundamental elements of microtubule dynamic instability, whereby switching can be brought about by a range of allosteric effectors, propagate deep within the lattice of assembled MTs, and profoundly affect MT function. Here, we review evidence for structural switching within the MT lattice and discuss current ideas about its mechanisms.
Current understanding of heparanase 2 regulation, a non-heparanase.
Becker Y, Haller H
Biochem Soc Trans · 2025 Feb · PMID 39910799 · Full text
Heparan sulfate (HS) proteoglycans are life-supporting proteins comprising a core protein to which one or more HS glycan chains are covalently bound. HS proteoglycans act as binding sites for circulating cells and molecu...
Heparan sulfate (HS) proteoglycans are life-supporting proteins comprising a core protein to which one or more HS glycan chains are covalently bound. HS proteoglycans act as binding sites for circulating cells and molecules, allow gradient formation, and provide local storage capacities. They act as coreceptors, fine-tuning growth factor receptors and activating intracellular signaling pathways. HS glycan chains are cleaved and regulated by heparanase 1 (Hpa1). Heparanase 2 (Hpa2) is a close homolog of Hpa1. Unlike Hpa1, Hpa2 lacks enzymatic activity but nonetheless binds HS with high affinity, thus modulating HS-mediated biological processes. Only a few functions of Hpa2 have been unraveled. Under disease conditions that include the Mendelian urofacial syndrome, Hpa2 expression is markedly down-regulated, most compellingly demonstrated in several cancers. Hpa2 also circulates in the bloodstream, potentially originating from secretory organs such as liver and pancreas. The promotor is inducible by cellular stressors including cytotoxic, proteostatic, and endoplasmic reticulum stress. Activating transcription factor 3 (ATF3) induces gene expression. We summarize Hpa2 regulation in the framework of health and disease to foster research into its function. The underlying mystery remains: ‘How does this “heparanase,” which is actually a non-heparanase, work, and what are the ramifications?
Exploring genome-transcriptome correlations in cancer.
Ronemus M, Bradford D, Laster Z … +1 more , Li S
Biochem Soc Trans · 2025 Feb · PMID 39910794 · Full text
We examine the complex relationship between genomic copy number variation (CNV) and gene expression, highlighting the relevance to cancer biology and other biological contexts. By tracing the history of genometranscripto...
We examine the complex relationship between genomic copy number variation (CNV) and gene expression, highlighting the relevance to cancer biology and other biological contexts. By tracing the history of genometranscriptome correlations, we emphasize the complexity and challenges in understanding these interactions, particularly within the heterogeneous landscape of human cancers. Recent advances in computational algorithms and high-throughput single-cell multi-omic sequencing technologies are discussed, demonstrating their potential to refine our understanding of cancer biology and their limitations. The integration of genomic and transcriptomic analyses, which offers novel insights into tumor evolution and heterogeneity as well as therapeutic strategies, is presented as a crucial approach for advancing cancer research.
Activation is only the beginning: mechanisms that tune kinase substrate specificity.
Clark LK, Cullati SN
Biochem Soc Trans · 2025 Feb · PMID 39907081 · Publisher ↗
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,...
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.
Microscopy methods for the in vivo study of nanoscale nuclear organization.
Lokesh NR, Pownall ME
Biochem Soc Trans · 2025 Feb · PMID 39898979 · Full text
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 fa...
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.
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