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PubMed2026

Acidic transcription factors position the genome at nuclear speckles through transcription-dependent and -independent mechanisms.

A small fraction of the genome reproducibly positions near nuclear speckles (NSs), increasing the expression and/or splicing efficiency of NS-associated genes. How specific genomic regions in mammalian cells are targeted to NSs remains unclear. Here, we demonstrate the establishment of genome-wide NS association without active transcription. We show that DNA sequences derived from NS-associated regions, when integrated as transgenes, are autonomously targeted to NSs. By systematically dissecting one such genomic locus, the COL1A1-SGCA locus, we identified redundant NS-targeting cis-regulatory elements, including an ∼600-bp fragment with 17 binding motifs for 8 transcription factors (TFs). Four NS-targeting TFs within this fragment contain acidic activation domains (AADs) that provide both chromatin-context and transcription-dependent NS targeting, properties that appear to be common among several other tested AADs. A subset of acidic activator TFs contains an additional, transcription-independent NS-targeting activity. Our findings establish diverse and partially redundant NS-targeting activities, which may facilitate dynamic gene positioning at the NS periphery for context-specific transcriptional responses.

Transcription, Genetic↗

PubMed2026

Expansion of the allelic and phenotypic spectrum of MED25-related developmental disorder: novel compound heterozygous variants with structural domain implications.

MED25-related developmental disorder (Basel-Vanagaite-Smirin-Yosef syndrome) is a rare autosomal recessive disorder, defined by severe neurodevelopmental delay, corpus callosum abnormalities, ocular involvement, epilepsy, and marked facial appearance. MED25 pathogenic variants interfere with the functioning of the Mediator complex, which is responsible for RNA polymerase II transcription. We report a 9-year-old girl who presents with significant global developmental delay, agenesis of the corpus callosum, congenital cataracts, epilepsy, hypotonia, musculoskeletal abnormalities, and typical craniofacial features. Trio-based whole-exome sequencing revealed compound heterozygous variants in MED25: a maternally transmitted truncating variant (c.1366 C > T; p.Gln456*) and a paternally inherited missense variant (c.430 C > T; p.Leu144Phe). The new classification of the missense variant as potentially pathogenic is supported by a systematic ACMG re-evaluation supported by segregation analysis, phenotypic specificity, computational prediction, and structural localization in the MED25 Activator Interaction Domain (ACID). Comparative phenotypic analyses show strong agreement with reported cases but add more data to fine-tune clinical spectrum. This article broadens the allelic and phenotypic spectrum of MED25-related developmental disorder and highlights the need for comprehensive evaluation across molecular, structural, and phenotypic pathways to elucidate variant signature in rare genetic disease models correctly.

Humans↗

PubMed2026

Active Site Assembly by SMG5 as a Mechanism for SMG6 Endonuclease Licencing in Nonsense-mediated mRNA Decay.

Nonsense-mediated mRNA decay (NMD) is a conserved eukaryotic surveillance pathway that eliminates transcripts containing premature termination codons (PTCs). Substantial progress has been made in defining the transcript features that mark aberrant translation termination for NMD activation, yet key mechanistic steps remain incompletely understood - including how recruitment of the central NMD factor UPF1 is coupled to the downstream effector phase in which targeted mRNAs are nucleolytically degraded. In metazoans, NMD employs an endonucleolytic route mediated by SMG6, a PIN-domain nuclease, alongside SMG5 and SMG7, which act downstream of PTC recognition. SMG5 has recently been proposed to licence SMG6 activity, yet the molecular basis of this licencing has remained elusive. Here, we combine AlphaFold structural predictions with biochemical assays to investigate interactions among human SMG5, SMG6, and SMG7. Structural models predict a high-confidence interface between SMG5 and SMG6 PIN domains that forms a composite active site: a conserved SMG5 aspartate (D893) complements the SMG6 acidic triad to reinstate the canonical tetrad required for PIN-domain catalysis. In vitro, SMG6 alone exhibits weak endonucleolytic activity, which is enhanced ∼10-fold by the SMG5 PIN domain. Mutational analyses confirm that conserved residues from both proteins are essential for this composite configuration. Our findings reveal that the SMG5 PIN domain, previously considered catalytically inert, plays a critical role in activating SMG6 by completing its active site. This work provides mechanistic insight into the SMG5-dependent licencing step and uncovers a composite PIN nuclease architecture at the heart of the metazoan NMD effector phase.

Nonsense Mediated mRNA Decay↗

PubMed2004

Dlx3 transcriptional regulation of osteoblast differentiation: temporal recruitment of Msx2, Dlx3, and Dlx5 homeodomain proteins to chromatin of the osteocalcin gene.

Genetic studies show that Msx2 and Dlx5 homeodomain (HD) proteins support skeletal development, but null mutation of the closely related Dlx3 gene results in early embryonic lethality. Here we find that expression of Dlx3 in the mouse embryo is associated with new bone formation and regulation of osteoblast differentiation. Dlx3 is expressed in osteoblasts, and overexpression of Dlx3 in osteoprogenitor cells promotes, while specific knock-down of Dlx3 by RNA interference inhibits, induction of osteogenic markers. We characterized gene regulation by Dlx3 in relation to that of Msx2 and Dlx5 during osteoblast differentiation. Chromatin immunoprecipitation assays revealed a molecular switch in HD protein association with the bone-specific osteocalcin (OC) gene. The transcriptionally repressed OC gene was occupied by Msx2 in proliferating osteoblasts, while Dlx3, Dlx5, and Runx2 were recruited postproliferatively to initiate transcription. Dlx5 occupancy increased over Dlx3 in mature osteoblasts at the mineralization stage of differentiation, coincident with increased RNA polymerase II occupancy. Dlx3 protein-DNA interactions stimulated OC promoter activity, while Dlx3-Runx2 protein-protein interaction reduced Runx2-mediated transcription. Deletion analysis showed that the Dlx3 interacting domain of Runx2 is from amino acids 376 to 432, which also include the transcriptionally active subnuclear targeting sequence (376 to 432). Thus, we provide cellular and molecular evidence for Dlx3 in regulating osteoprogenitor cell differentiation and for both positive and negative regulation of gene transcription. We propose that multiple HD proteins in osteoblasts constitute a regulatory network that mediates development of the bone phenotype through the sequential association of distinct HD proteins with promoter regulatory elements.

Amino Acid Sequence↗

PubMed2026

Pervasive phosphorylation by phage T7 kinase disarms bacterial defences.

Bacteria and bacteriophages are in a constant arms race to develop defence and anti-defence systems, respectively. Currently known phage-encoded anti-defence systems are specific to the activity of the targeted bacterial defence system. Here we identify a mechanism by which the T7 bacteriophage broadly counteracts bacterial defences using protein phosphorylation. Its kinase (T7K), which has been reported to redirect the function of a few host proteins1-5, is actually a hyperpromiscuous dual-specificity kinase that phosphorylates nearly all host and phage proteins during infection. The scale of phosphorylation vastly exceeds known phosphosites in Escherichia coli, has no sequence motif specificity and results in a higher proteome-wide phosphorylation density than mammalian cells with around 500 kinases. Stoichiometry analysis of phosphorylation sites revealed strong bias in T7K activity towards nucleic-acid-binding substrates mediated by its C-terminal DNA-binding domain. This highly stoichiometric phosphorylation enables the deactivation of DNA-targeting or DNA-containing bacterial defence systems. We provide mechanistic insights into how T7K weakens DNA-containing Retron-Eco9 through specific phosphorylation events, with single phosphomimetic mutations in key sites of the toxin abolishing defence. Moreover, by screening a large collection of E. coli strains, we provide evidence of broad anti-defence abilities of T7K in nature, as counteracted strains contain diverse bacterial defence systems. T7K homologues are found almost exclusively in phages, with hyperpromiscuous kinase activity probably being enabled by a divergent DFG-like motif in the catalytic centre.

Journal Article↗

PubMed2026

Physiological sub-typing of cold and freezing injury in Triticum turgidum subspecies with bioinformatic and expression characterization of glutathione reductase.

BACKGROUND: This study examined how different subspecies of Triticum turgidum (T. durum, T. polonicum, T. turanicum) respond to cold and freezing, assessing their water status, stress responses, and antioxidant system, with particular focus on the structure and function of glutathione reductase (TtGR). METHODS: TtGR genes were first identified from the T. turgidum genome using publicly available genomic resources such as Ensembl Plants. Promoter regions (~2 kb upstream) were analyzed to identify cis-regulatory elements using PlantCARE. Gene classification was performed based on predicted subcellular localization and conserved domain features. Plants were subjected to cold acclimation and freezing treatments, and physiological, biochemical, and enzymatic parameters were measured. RESULTS: Bioinformatics analyses identified four TtGR genes in the T. turgidum genome. The genes in two groups: cytosolic (Class I) and chloroplastic (Class II). Gene structure analysis showed a conserved exon-intron organization, while motif analysis confirmed the presence of Nicotinamide Adenine Dinucleotide Phosphate (NADPH)-binding and redox-active domains across all TtGR proteins. Several regulatory sequences in the promoters are involved in cold (DRE), abscisic acid (ABRE), and stress (STRE) responses, indicating that TtGR genes are dynamically regulated in response to environmental changes. Physiological analyses showed that freezing treatment reduces leaf water content in all genotypes, leading to turgor loss, hydrogen peroxide (H2O2) accumulation, and increased malondealdehyte (MDA) levels. However, tolerance mechanisms addressing water stress and membrane damage differ among genotypes. At the biochemical level, activation of the antioxidant defense system occurs in all genotypes. T. turanicum displays strong defense by significantly increasing enzyme activities, ensuring that the ascorbate-glutathione cycle continues under stress. By contrast, T. polonicum, although showing increased overall enzyme activities, experiences a dramatic drop in glutathione reductase (GR) activity at freezing temperatures, which restricts reduced glutathione (GSH) regeneration and creates a functional bottleneck in the antioxidant cycle. T. durum fails to sustain enzyme activities over the stress period, leading to an intermediate-sensitive response. Thus, whereas T. turanicum effectively maintains antioxidant function during freezing, T. polonicum and T. durum exhibit less efficient stress responses, either through enzymatic bottlenecks or a lack of sustained defense. CONCLUSIONS: One of the most striking findings of this study is the observed dissociation between TtGR gene expression levels and enzyme activities. Low temperature limits the link between transcription and enzyme function. The primary determinant of low-temperature tolerance in T. turgidum subspecies is the sustainability of GR enzyme activity and GSH regeneration under freezing conditions.

Triticum↗

PubMed2010

CCDC6 represses CREB1 activity by recruiting histone deacetylase 1 and protein phosphatase 1.

RET/papillary thyroid carcinoma 1 (PTC1) oncogene is frequently activated in human PTCs. It is characterized by the fusion of the intracellular kinase-encoding domain of RET to the first 101 amino acids of CCDC6. The aim of our work is to characterize the function of the CCDC6 protein to better understand the function of its truncation, that results in the loss of the expression of one allele, in the process of thyroid carcinogenesis. Here, we report that CCDC6 interacts with CREB1 and represses its transcriptional activity by recruiting histone deacetylase 1 and protein phosphatase 1 proteins at the CRE site of the CREB1 target genes. Finally, we show an increased CREB1 phosphorylation and activity in PTCs carrying the RET/PTC1 oncogene. Consistently, an increased expression of two known CREB1 target genes, AREG and cyclin A, was observed in this subgroup of thyroid papillary carcinomas. Therefore, the repression of CREB1 activity by CCDC6 has a critical function in the development of human thyroid papillary carcinomas carrying RET/PTC1 activation.

Amphiregulin↗

PubMed2025

Molecular Characterization of the Group A Streptococcus Virulence-Regulatory System FasBCAX.

By regulating the assortment and abundance of its virulence factors at different anatomic sites, the group A Streptococcus (GAS) can cause a range of human diseases. The Fas regulatory system is encoded by a four-gene locus, fasBCAX, with fasX encoding the FasX small regulatory RNA effector molecule. FasX post-transcriptionally regulates target mRNAs through well-characterized mechanisms. Less characterized are the layers of regulation that occur upstream of FasX activity, such as how the products of the fasBCA genes enhance FasX abundance 100-fold. Here, we present data consistent with FasBCA forming a three-component regulatory system, with FasBC being sensor kinase-like proteins that, upon recognizing one or more signals, heterodimerize and phosphorylate FasA, with phosphorylated FasA binding to the fasX promoter and inducing transcription. We identified key amino acids involved in phosphate flow, including H246 of FasC and D60 of FasA, and demonstrated that certain domains (e.g., the kinase domain of FasC) are dispensable for activity. Additionally, we show that a proteinaceous factor within human plasma activates the Fas system. This work represents the first molecular analysis of the Fas proteins which, by modulating FasX levels, play a critical role in the ability of GAS to coordinately regulate virulence factor production.

Streptococcus pyogenes↗

PubMed2025

AFL1 is a phosphoinositide phosphate- and actin-binding protein.

At14a-Like 1 (AFL1) is highly induced during low water potential stress and remains at high levels during stress acclimation. AFL1, and the closely related At14a, are plant-specific proteins that have limited similarity to mammalian actin- and membrane-associated proteins. Previous research indicated that manipulation of AFL1 expression affects actin cytoskeleton dynamics and endocytic trafficking (as measured by uptake of membrane dye FM4-64). However, it has remained unclear whether this is a direct activity of AFL1 or an indirect effect. We found that AFL1 specifically bound actin filaments as well as the phosphoinositide phosphates (PIPs) phosphoinositide-3-monophosphate [PI(3)P], PI(5)P, and the diphosphate PI(3,5)P2 in co-sedimentation and PIP strip membrane assays, respectively. Interestingly, these binding activities were mediated by the same site within the C-terminal domain of AFL1. Mutation of a single amino acid in the AFL1 C-terminal domain was sufficient to disrupt both actin filament and PIP binding in vitro and to disrupt accumulation of the mutated protein in transgenic plants. We also found that the central hydrophobic region of AFL1 was required for AFL1 co-localization with actin filaments and plasma membrane. Mutation of AFL1 and At14a using genome editing confirmed that loss of these proteins reduced growth during low water potential stress and resulted in less extensive actin filament arrays and disrupted FM4-64 uptake. Together these observations indicate that AFL1 can directly participate in cytoskeleton organization and membrane dynamics via PIP and actin filament binding.

Arabidopsis↗

PubMed2026

Developmental analysis of the cone photoreceptor-less little skate retina reveals distinct Onecut1 isoforms.

The retinal development of elasmobranchs, the subclass comprising sharks, skates, and rays, remains poorly understood. This group is diverse in retinal phenotype, with many sharks and rays possessing rods together with one or more cone types. In contrast, the little skate (Leucoraja erinacea) has only a single rod photoreceptor type, which has been reported to exhibit some physiological and anatomical properties associated with cones. To investigate how this unusual photoreceptor system develops, we first identified an embryonic stage of early photoreceptor formation based on otx2 expression. We then developed a retinal electroporation approach to test whether a onecut1-dependent cone-associated reporter could be activated in the embryonic skate retina. Activation of this reporter was not detected, indicating that the corresponding enhancer is not robustly active under the conditions tested. To assess developmental changes in gene expression, we generated bulk RNA-seq datasets from embryonic, hatchling, and adult retinas. These analyses showed strong embryonic expression of onecut1, increasing expression of rod-associated genes through development, and pseudogenization or loss of multiple cone-enriched genes. We further identified a developmentally regulated onecut1 splice isoform containing an additional 48 amino acid sequence between the CUT and homeodomain DNA-binding domains. This spacer-containing isoform, termed LSOC1X2, was most abundant in the embryonic retina. To test whether LSOC1X2 retained regulatory activity, we assayed it in a mouse retinal reporter system. Both skate Onecut1 isoforms activated the ThrbCRM1 reporter in this heterologous context. Together, these findings identify a novel, developmentally regulated retinal onecut1 isoform in the little skate and establish it as a candidate regulator for future studies of photoreceptor development in this species and its elasmobranch relatives.

Animals↗

PubMed2002

Control of the hypoxic response in Drosophila melanogaster by the basic helix-loop-helix PAS protein similar.

In mammalian systems, the heterodimeric basic helix-loop-helix (bHLH)-PAS transcription hypoxia-inducible factor (HIF) has emerged as the key regulator of responses to hypoxia. Here we define a homologous system in Drosophila melanogaster, and we characterize its activity in vivo during development. By using transcriptional reporters in developing transgenic flies, we show that hypoxia-inducible activity rises to a peak in late embryogenesis and is most pronounced in tracheal cells. We show that the bHLH-PAS proteins Similar (Sima) and Tango (Tgo) function as HIF-alpha and HIF-beta homologues, respectively, and demonstrate a conserved mode of regulation for Sima by oxygen. Sima protein, but not its mRNA, was upregulated in hypoxia. Time course experiments following pulsed ectopic expression demonstrated that Sima is stabilized in hypoxia and that degradation relies on a central domain encompassing amino acids 692 to 863. Continuous ectopic expression overrode Sima degradation, which remained cytoplasmic in normoxia, and translocated to the nucleus only in hypoxia, revealing a second oxygen-regulated activation step. Abrogation of the Drosophila Egl-9 prolyl hydroxylase homologue, CG1114, caused both stabilization and nuclear localization of Sima, indicating a central involvement in both processes. Tight conservation of the HIF/prolyl hydroxylase system in Drosophila provides a new focus for understanding oxygen homeostasis in intact multicellular organisms.

Active Transport, Cell Nucleus↗

PubMed2002

The ETS domain transcription factor Elk-1 contains a novel class of repression domain.

The ETS domain transcription factor Elk-1 serves as an integration point for different mitogen-activated protein (MAP) kinase pathways. Phosphorylation of Elk-1 by MAP kinases triggers its activation. However, while the activation process is well understood, its downregulation-inactivation is less well characterized. The ETS DNA-binding domain plays a role in the downregulation of Elk-dependent promoter activity following mitogenic activation by recruiting the mSin3A-HDAC complex. Here we have identified a novel evolutionarily conserved repression domain in Elk-1, termed the R motif, which serves to reduce the basal transcriptional activity of Elk-1 and dampen its response to mitogenic signals. This domain is highly potent and portable and can repress transcription in trans. The R motif is related to the CRD1 repression domain in p300 and can functionally replace this domain and confer p21(waf1/cip1) inducibility on p300. However, the R motif acts in a context-dependent manner and is not p21(waf1/cip1) responsive in Elk-1. Thus, the Elk-1 R motif and the p300 CRD1 motif represent a new class of repression domains that are regulated in a context-dependent manner.

Amino Acid Motifs↗

PubMed2026

Functions of tandem-repeat galectins and domain coordination governs galectin-4 activity in grass carp (Ctenopharyngodon idella).

Galectins are β-galactoside-binding lectins that play essential roles in innate immunity. Among them, tandem-repeat galectins (TrGals), typically composed of two distinct carbohydrate-recognition domains (CRDs) connected by a linker peptide, are well established as key regulators of pathogen recognition and host defense in mammals. However, their structural diversity and immunological functions in teleost fish remain poorly understood. In this study, five TrGals (Gal-4, Gal-8a, Gal-8b, Gal-9, and Gal-9like) were identified in grass carp. Sequence and structural analysis revealed that Gal-8a/b, Gal-9, and Gal-9like possess the canonical two-CRD architecture, whereas Gal-4 uniquely contains four highly similar tandem-repeat domains. All five TrGals were broadly expressed across examined tissues, with predominant expression in the liver. Upon Aeromonas hydrophila infection, Gal-4, Gal-8a, Gal-8b, and Gal-9 were rapidly up-regulated at early time points (3-6 h). To elucidate the functional significance of CRD number, recombinant full-length CiGal-4 (CiGal4-full) and three truncated variants containing one, two, or three CRDs (CiGal4-1CRD, CiGal4-2CRD, and CiGal4-3CRD) were generated and systematically characterized. All recombinant proteins contained the conserved β-sheet structure typical of galectin CRDs. Functional assays revealed that CiGal4-full displayed the strongest growth-inhibitory activity against all tested bacteria, whereas CiGal4-1CRD showed the weakest effect. Notably, CiGal4-2CRD exhibited the most potent bactericidal activity, surpassing the full-length protein, while CiGal4-3CRD showed no further enhancement. CiGal4-full and CiGal4-2CRD showed superior carbohydrate-binding activities compared with the other variants. Collectively, these results reveal that CRD copy number alone does not linearly determine galectin function. Instead, domain organization and conformational coordination are critical for optimizing antimicrobial activity. This study provides new insights into the structure-function relationships and evolutionary diversification of galectins in teleosts and highlights their potential as novel antimicrobial and immunomodulatory agents in aquaculture.

Animals↗

PubMed2026

Viral replication through phase separation: Cytosolic and nuclear condensates.

Replication of many RNA and DNA viruses occurs within specialized intracellular hubs organized as membraneless biomolecular condensates (BCs) driven by liquid-liquid phase separation. As obligate intracellular parasites, viruses depend on the host cell machinery to complete their replication cycles and therefore actively remodel the intracellular environment to favor viral genome replication, transcription, and assembly. Cytosolic and nuclear phase-separated replication compartments (RC) provide concentrated and dynamic platforms that promote efficient interactions between viral genomes and viral or host proteins essential for infection. The formation of viral replication BCs is typically facilitated by viral proteins enriched in intrinsically disordered regions and low-complexity domains, which enable multivalent interactions with viral nucleic acids and cellular factors. These interactions are mediated by diverse biophysical forces, including hydrophobic and π interactions, hydrogen bonding, molecular crowding, and osmotic effects. Throughout infection, viral BCs remain highly dynamic, allowing continuous exchange of components and functional maturation of replication hubs. Their properties and activities are further regulated by post-translational modifications of viral and host proteins, such as phosphorylation, acetylation, and methylation. In this review, we summarize current evidence supporting liquid-liquid phase separation as a central organizing principle of viral RCs. We focus on representative RNA and DNA viruses that replicate in the cytosol or nucleus, highlighting virus-specific strategies, conserved mechanisms, and the consequences of BC formation for viral replication efficiency, host antiviral responses, and therapeutic intervention.

Phase Separation↗

PubMed2026

A novel domain of unknown function 707 protein coordinates root growth and drought tolerance.

A well-developed root system is one of the morphological mechanisms through which xerophytes adapt to drought. However, the molecular mechanisms underlying root growth are not completely known. In this work, two domain of unknown function 707 (DUF707) proteins were identified as hub genes for the response of roots to drought stress in Lespedeza potaninii, a xerophytic subshrub. We found that angiosperm DUF707 proteins can be divided into two subfamilies. LpDUF707-1 expression was strongly induced under drought stress and abscisic acid (ABA) treatment in the roots of L. potaninii, and its promoter activity in the roots was significantly induced by drought stress and mannitol treatments. The overexpression of LpDUF707-1 significantly improved root growth and drought tolerance, whereas the silencing of LpDUF707-1 inhibited root growth and reduced drought tolerance. We further revealed that the LpOBP3.1 transcription factor directly binds to the promoter region of LpDUF707-1, thereby repressing its activity. LpOBP3.1 expression was strongly suppressed under drought stress and ABA treatment in the roots of L. potaninii. The overexpression of LpOBP3.1 significantly inhibited root growth and decreased drought tolerance, whereas LpOBP3.1-RNAi lines presented the opposite pattern. Collectively, our results demonstrated that this novel module regulates root growth and drought tolerance in L. potaninii, thus providing gene targets for the development of elite crop varieties with well-developed root-mediated drought tolerance.

Drought Resistance↗

PubMed2026

Unlocking antifungal mechanisms of natural 3-(oxazole-5-yl) indole compound derived from Streptomyces syringium against plant gray mold caused by Botrytis cinerea.

BACKGROUND: Plant fungal diseases cause significant agricultural losses, and Streptomyces-derived antifungal compounds offer a promising biocontrol strategy. This study aimed to isolate and characterize bioactive metabolites from Streptomyces syringium LZ036 and evaluate their activity and mechanism of action against Botrytis cinerea. RESULTS: A strain LZ036 with broad-spectrum antifungal activity was identified as Streptomyces syringium. The 3-(oxazole-5-yl) indole compound NL3 isolated from this strain exhibited potent broad-spectrum antifungal activity, especially against Botrytis cinerea. Compound NL3 inhibited fungal growth and development by inducing severe oxidative damage and membrane disruption. And it could trigger jasmonic acid (JA)-dependent induced systemic resistance (ISR) in plants. Transcriptomic analysis of compound NL3-treated Botrytis cinerea revealed genome-wide transcriptional alterations, including disruption of energy metabolism and mitochondrial function. Key genes related to mitogen-activated protein kinase (MAPK) signaling pathway down-regulated significantly, among which the catalytic S_TKc domain of Bcste7 exhibited a predicted interaction with compound NL3 through hydrophobic interactions and hydrogen bonding. CONCLUSION: The Streptomyces syringium-derived compound NL3 shows high potential as a green fungicide, acting through multiple mechanisms. These findings advance the development of Streptomyces-based antifungal agents. © 2026 Society of Chemical Industry.

3‐(oxazole‐5‐yl) indole compo↗

PubMed2004

SUMO and ubiquitin in the nucleus: different functions, similar mechanisms?

The small ubiquitin-related modifier SUMO posttranslationally modifies many proteins with roles in diverse processes including regulation of transcription, chromatin structure, and DNA repair. Similar to nonproteolytic roles of ubiquitin, SUMO modification regulates protein localization and activity. Some proteins can be modified by SUMO and ubiquitin, but with distinct functional consequences. It is possible that the effects of ubiquitination and SUMOylation are both largely due to binding of proteins bearing specific interaction domains. Both modifications are reversible, and in some cases dynamic cycles of modification may be required for activity. Studies of SUMO and ubiquitin in the nucleus are yielding new insights into regulation of gene expression, genome maintenance, and signal transduction.

Amino Acid Sequence↗

PubMed2026

LitCTL1: A novel C-type lectin involved in the mucosal and cellular immunity of the common periwinkle Littorinalittorea.

C-type lectins (CTLs) are vital pattern-recognition receptors (PRRs) that mediate innate immune responses in mollusks, yet their characterization in Caenogastropoda, the largest gastropod group, remains limited. This study characterizes LitCTL1, a novel secreted single-domain C-type lectin from the common periwinkle, Littorina littorea. The 199-amino acid polypeptide contains a conserved carbohydrate recognition domain with canonical QPD and WND motifs and is predicted to form a homodimer. Uniquely, LitCTL1 was localized in both circulating hemocytes and mucus-secreting epithelial cells of the foot, mantle, and hypobranchial gland - the first report of such dual localization for a molluscan lectin, linking systemic and mucosal defense. Expression analysis revealed that LitCTL1 is constitutively expressed in hemocytes. Functional assays with recombinant LitCTL1 demonstrated its role as a potent opsonin with hemagglutinating activity, significantly enhancing hemocyte spreading and the phagocytosis of zymosan. Genomic analysis reveals that LitCTL1 belongs to a rapidly diversifying, genus-specific expansion distinct from conserved perlucin-like lineages. These results identify LitCTL1 as a key effector molecule in both systemic and mucosal innate immunity, likely reflecting an evolutionary adaptation to the microbial challenges of the intertidal environment.

Animals↗