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Keywords = protein subunits

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21 pages, 3840 KiB  
Article
Identification of CaVβ1 Isoforms Required for Neuromuscular Junction Formation and Maintenance
by Amélie Vergnol, Aly Bourguiba, Stephanie Bauché, Massiré Traoré, Maxime Gelin, Christel Gentil, Sonia Pezet, Lucile Saillard, Pierre Meunier, Mégane Lemaitre, Julianne Perronnet, Frederic Tores, Candice Gautier, Zoheir Guesmia, Eric Allemand, Eric Batsché, France Pietri-Rouxel and Sestina Falcone
Cells 2025, 14(15), 1210; https://doi.org/10.3390/cells14151210 (registering DOI) - 6 Aug 2025
Abstract
Voltage-gated Ca2+ channels (VGCCs) are regulated by four CaVβ subunits (CaVβ1–CaVβ4), each showing specific expression patterns in excitable cells. While primarily known for regulating VGCC function, CaVβ proteins also have channel-independent roles, including gene expression modulation. Among these, CaVβ1 is expressed in [...] Read more.
Voltage-gated Ca2+ channels (VGCCs) are regulated by four CaVβ subunits (CaVβ1–CaVβ4), each showing specific expression patterns in excitable cells. While primarily known for regulating VGCC function, CaVβ proteins also have channel-independent roles, including gene expression modulation. Among these, CaVβ1 is expressed in skeletal muscle as multiple isoforms. The adult isoform, CaVβ1D, localizes at the triad and modulates CaV1 activity during Excitation–Contraction Coupling (ECC). In this study, we investigated the lesser-known embryonic/perinatal CaVβ1 isoforms and their roles in neuromuscular junction (NMJ) formation, maturation, and maintenance. We found that CaVβ1 isoform expression is developmentally regulated through differential promoter activation. Specifically, CaVβ1A is expressed in embryonic muscle and reactivated in denervated adult muscle, alongside the known CaVβ1E isoform. Nerve injury in adult muscle triggers a shift in promoter usage, resulting in re-expression of embryonic/perinatal Cacnb1A and Cacnb1E transcripts. Functional analyses using aneural agrin-induced AChR clustering on primary myotubes demonstrated that these isoforms contribute to NMJ formation. Additionally, their expression during early post-natal development is essential for NMJ maturation and long-term maintenance. These findings reveal previously unrecognized roles of CaVβ1 isoforms beyond VGCC regulation, highlighting their significance in neuromuscular system development and homeostasis. Full article
(This article belongs to the Section Tissues and Organs)
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23 pages, 3314 KiB  
Article
Functional Express Proteomics for Search and Identification of Differentially Regulated Proteins Involved in the Reaction of Wheat (Triticum aestivum L.) to Nanopriming by Gold Nanoparticles
by Natalia Naraikina, Tomiris Kussainova, Andrey Shelepchikov, Alexey Tretyakov, Alexander Deryabin, Kseniya Zhukova, Valery Popov, Irina Tarasova, Lev Dykman and Yuliya Venzhik
Int. J. Mol. Sci. 2025, 26(15), 7608; https://doi.org/10.3390/ijms26157608 (registering DOI) - 6 Aug 2025
Abstract
Proteomic profiling using ultrafast chromatography–mass spectrometry provides valuable insights into plant responses to abiotic factors by linking molecular changes with physiological outcomes. Nanopriming, a novel approach involving the treatment of seeds with nanoparticles, has demonstrated potential for enhancing plant metabolism and productivity. However, [...] Read more.
Proteomic profiling using ultrafast chromatography–mass spectrometry provides valuable insights into plant responses to abiotic factors by linking molecular changes with physiological outcomes. Nanopriming, a novel approach involving the treatment of seeds with nanoparticles, has demonstrated potential for enhancing plant metabolism and productivity. However, the molecular mechanisms underlying nanoparticle-induced effects remain poorly understood. In this study, we investigated the impact of gold nanoparticle (Au-NP) seed priming on the proteome of wheat (Triticum aestivum L.) seedlings. Differentially regulated proteins (DRPs) were identified, revealing a pronounced reorganization of the photosynthetic apparatus (PSA). Both the light-dependent reactions and the Calvin cycle were affected, with significant upregulation of chloroplast-associated protein complexes, including PsbC (CP43), chlorophyll a/b-binding proteins, Photosystem I subunits (PsaA and PsaB), and the γ-subunit of ATP synthase. The large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCo) exhibited over a threefold increase in expression in Au-NP-treated seedlings. The proteomic changes in the large subunit RuBisCo L were corroborated by transcriptomic data. Importantly, the proteomic changes were supported by physiological and biochemical analyses, ultrastructural modifications in chloroplasts, and increased photosynthetic activity. Our findings suggest that Au-NP nanopriming triggers coordinated molecular responses, enhancing the functional activity of the PSA. Identified DRPs may serve as potential biomarkers for further elucidation of nanopriming mechanisms and for the development of precision strategies to improve crop productivity. Full article
(This article belongs to the Special Issue Molecular Research and Applications of Nanomaterials)
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19 pages, 3503 KiB  
Article
Discovery of Hub Genes Involved in Seed Development and Lipid Biosynthesis in Sea Buckthorn (Hippophae rhamnoides L.) Using UID Transcriptome Sequencing
by Siyang Zhao, Chengjiang Ruan, Alexey A. Dmitriev and Hyun Uk Kim
Plants 2025, 14(15), 2436; https://doi.org/10.3390/plants14152436 (registering DOI) - 6 Aug 2025
Abstract
Sea buckthorn is a vital woody oil species valued for its role in soil conservation and its bioactive seed oil, which is rich in unsaturated fatty acids and other compounds. However, low seed oil content and small seed size are the main bottlenecks [...] Read more.
Sea buckthorn is a vital woody oil species valued for its role in soil conservation and its bioactive seed oil, which is rich in unsaturated fatty acids and other compounds. However, low seed oil content and small seed size are the main bottlenecks restricting the development and utilization of sea buckthorn. In this study, we tested the seed oil content and seed size of 12 sea buckthorn cultivars and identified the key genes and transcription factors involved in seed development and lipid biosynthesis via the integration of UID RNA-seq (Unique Identifiers, UID), WGCNA (weighted gene co-expression network analysis) and qRT-PCR (quantitative real-time PCR) analysis. The results revealed five cultivars (CY02, CY11, CY201309, CY18, CY21) with significantly higher oil contents and five cultivars (CY10, CY201309, CY18, CY21, CY27) with significantly heavier seeds. A total of 10,873 genes were significantly differentially expressed between the S1 and S2 seed developmental stages of the 12 cultivars. WGCNA was used to identify five modules related to seed oil content and seed weight/size, and 417 candidate genes were screened from these modules. Among them, multiple hub genes and transcription factors were identified; for instance, ATP synthase, ATP synthase subunit D and Acyl carrier protein 1 were related to seed development; plastid–lipid-associated protein, acyltransferase-like protein, and glycerol-3-phosphate 2-O-acyltransferase 6 were involved in lipid biosynthesis; and transcription factors DOF1.2, BHLH137 and ERF4 were associated with seed enlargement and development. These findings provide crucial insights into the genetic regulation of seed traits in sea buckthorn, offering targets for future breeding efforts aimed at improving oil yield and quality. Full article
(This article belongs to the Special Issue Molecular Regulation of Seed Development and Germination)
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16 pages, 1898 KiB  
Article
Screening of qPCR Reference Genes in Quinoa Under Cold, Heat, and Drought Gradient Stress
by Qiuwei Lu, Xueying Wang, Suxuan Dong, Jinghan Fu, Yiqing Lin, Ying Zhang, Bo Zhao and Fuye Guo
Plants 2025, 14(15), 2434; https://doi.org/10.3390/plants14152434 - 6 Aug 2025
Abstract
Quinoa (Chenopodium quinoa), a stress-tolerant pseudocereal ideal for studying abiotic stress responses, was used to systematically identify optimal reference genes for qPCR normalization under gradient stresses: low temperatures (LT group: −2 °C to −10 °C), heat (HT group: 39° C to [...] Read more.
Quinoa (Chenopodium quinoa), a stress-tolerant pseudocereal ideal for studying abiotic stress responses, was used to systematically identify optimal reference genes for qPCR normalization under gradient stresses: low temperatures (LT group: −2 °C to −10 °C), heat (HT group: 39° C to 45 °C), and drought (DR group: 7 to 13 days). Through multi-algorithm evaluation (GeNorm, NormFinder, BestKeeper, the ΔCt method, and RefFinder) of eleven candidates, condition-specific optimal genes were established as ACT16 (Actin), SAL92 (IT4 phosphatase-associated protein), SSU32 (Ssu72-like family protein), and TSB05 (Tryptophan synthase beta-subunit 2) for the LT group; ACT16 and NRP13 (Asparagine-rich protein) for the HT group; and ACT16, SKP27 (S-phase kinase), and NRP13 for the DR group, with ACT16, NRP13, WLIM96 (LIM domain-containing protein), SSU32, SKP27, SAL92, and UBC22 (ubiquitin-conjugating enzyme E2) demonstrating cross-stress stability (global group). DHDPS96 (dihydrodipicolinate synthase) and EF03 (translation elongation factor) showed minimal stability. Validation using stress-responsive markers—COR72 (LT), HSP44 (HT), COR413-PM (LT), and DREB12 (DR)—confirmed reliability; COR72 and COR413-PM exhibited oscillatory cold response patterns, HSP44 peaked at 43 °C before declining, and DREB12 showed progressive drought-induced upregulation. Crucially, normalization with unstable genes (DHDPS96 and EF03) distorted expression profiles. This work provides validated reference standards for quinoa transcriptomics under abiotic stresses. Full article
(This article belongs to the Section Plant Response to Abiotic Stress and Climate Change)
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14 pages, 1669 KiB  
Article
Guinea Pig X Virus Is a Gammaherpesvirus
by Vy Ngoc Yen Truong, Robert Ellis and Brent A. Stanfield
Viruses 2025, 17(8), 1084; https://doi.org/10.3390/v17081084 - 5 Aug 2025
Abstract
The Guinea Pig X Virus (GPXV), a newly identified gammaherpesvirus, provides an opportunity to study viral evolution and host–virus dynamics. This study characterizes the GPXV genome and investigates its phylogenetic relationships and divergence from related viruses through comparative genomic and phylogenetic analyses. Virus [...] Read more.
The Guinea Pig X Virus (GPXV), a newly identified gammaherpesvirus, provides an opportunity to study viral evolution and host–virus dynamics. This study characterizes the GPXV genome and investigates its phylogenetic relationships and divergence from related viruses through comparative genomic and phylogenetic analyses. Virus propagation was conducted in Vero cells, followed by genomic DNA extraction and pan-herpesvirus nested PCR. Sanger sequencing filled gaps in the initial genome assembly, and whole-genome sequencing was performed using the Illumina MiSeq platform. Phylogenetic analyses focused on ORF8 (glycoprotein B), ORF9 (DNA polymerase catalytic subunit), ORF50 (RTA: replication and transcription activator), and ORF73 (LANA: latency-associated nuclear antigen). Results showed that GPXV ORFs showed variable evolutionary relationships with other gammaherpesviruses, including divergence from primate-associated viruses and clustering with bovine and rodent viruses. In addition to phylogenetics, a comprehensive comparative analysis of protein-coding genes between GPXV and the previously described Guinea Pig Herpes-Like Virus (GPHLV) revealed divergence. Twenty-four non-ORF genomic features were unique to GPXV, while 62 shared ORFs exhibited low to high sequence divergence. These findings highlight GPXV’s distinct evolutionary trajectory and its potential role as a model for studying host-specific adaptations and gammaherpesvirus diversity. Full article
(This article belongs to the Special Issue Animal Herpesvirus 2025)
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16 pages, 1921 KiB  
Article
A Bivalent mRNA Vaccine Efficiently Prevents Gammaherpesvirus Latent Infection
by Yannan Yin, Jinkai Zang, Huichun Shi, Zhuang Wang, Linlin Kuang, Shuxia Wang, Haikun Wang, Ning Li, Xiaozhen Liang and Zhong Huang
Vaccines 2025, 13(8), 830; https://doi.org/10.3390/vaccines13080830 (registering DOI) - 4 Aug 2025
Abstract
Background: It is still challenging to develop effective vaccines against tumorigenic human gammaherpesviruses such as Epstein–Barr virus (EBV). A major obstacle is the lack of a small animal model that reproduces the natural infection course of human gammaherpesviruses to allow for proper [...] Read more.
Background: It is still challenging to develop effective vaccines against tumorigenic human gammaherpesviruses such as Epstein–Barr virus (EBV). A major obstacle is the lack of a small animal model that reproduces the natural infection course of human gammaherpesviruses to allow for proper assessment of vaccine efficacy. Murine gammaherpesvirus 68 (MHV68) is a natural pathogen of wild rodents and laboratory mice and therefore can be used as a surrogate for human gammaherpesviruses to evaluate vaccination strategies. Methods: In this study, two mRNA vaccine candidates were generated, one encoding a fusion protein of the MHV68 gH with the gL (gHgL-mRNA) and the other expressing the MHV68 gB protein (gB-mRNA). The immunogenicity and protective efficacy of the mRNA vaccine candidates were evaluated in a mouse model of MHV68 infection. Results: The gHgL-mRNA but not the gB-mRNA candidate vaccine was able to induce neutralizing antibodies in mice, whereas both vaccines could elicit antigen-specific T-cell responses. Following MHV68 intranasal inoculation, complete blocking of the establishment of viral latency was observed in some mice immunized with individual gHgL-mRNA or gB-mRNA vaccines. Notably, co-immunization with the two mRNA vaccines appeared to be more effective than individual vaccines, achieving sterile immunity in 50% of the vaccinated mice. Conclusions: This study demonstrates that immunization with mRNA platform-based subunit vaccines is indeed capable of preventing MHV68 latent infection, thus validating a safe and efficacious vaccination strategy that may be applicable to human gammaherpesviruses. Full article
(This article belongs to the Special Issue The Development of mRNA Vaccines)
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14 pages, 1320 KiB  
Review
Elucidating the Role of CNOT2 in Regulating Cancer Cell Growth via the Modulation of p53 and c-Myc Expression
by Jihyun Lee, Ju-Ha Kim, Yu Jin Lee, Je Joung Oh, Yeo Jeong Han and Ji Hoon Jung
Curr. Issues Mol. Biol. 2025, 47(8), 615; https://doi.org/10.3390/cimb47080615 - 4 Aug 2025
Abstract
CNOT2, a central component of the CCR4-NOT transcription complex subunit 2, plays a pivotal role in the regulation of gene expression and metabolism. CNOT2 is involved in various cellular processes, including transcriptional regulation, mRNA deadenylation, and the modulation of mRNA stability. CNOT2 [...] Read more.
CNOT2, a central component of the CCR4-NOT transcription complex subunit 2, plays a pivotal role in the regulation of gene expression and metabolism. CNOT2 is involved in various cellular processes, including transcriptional regulation, mRNA deadenylation, and the modulation of mRNA stability. CNOT2 specifically contributes to the structural integrity and enzymatic activity of the CCR4-NOT complex with transcription factors and RNA-binding proteins. Recent studies have elucidated its involvement in cellular differentiation, immune response modulation, and the maintenance of genomic stability. Abnormal regulation of CNOT2 has been implicated in a spectrum of pathological conditions, including oncogenesis, neurodegenerative disorders, and metabolic dysfunctions. This review comprehensively examines the interplay between CNOT2 and p53, elucidating their collaborative and antagonistic interactions in various cellular contexts. CNOT2 is primarily involved in transcriptional regulation, mRNA deadenylation, and the modulation of mRNA stability, thereby influencing diverse biological processes such as cell proliferation, apoptosis, and differentiation. Conversely, p53 is renowned for its role in maintaining genomic integrity, inducing cell cycle arrest, apoptosis, and senescence in response to cellular stress and DNA damage. Emerging evidence suggests that CNOT2 can modulate p53 activity through multiple mechanisms, including the regulation of p53 mRNA stability and the modulation of p53 target gene expression. The dysregulation of CNOT2 and p53 interactions has been implicated in the pathogenesis and progression of various cancers, highlighting their potential as therapeutic targets. Additionally, CNOT2 regulates c-Myc, a well-known oncogene, in cancer cells. This review shows the essential roles of CNOT2 in maintaining cancer cellular homeostasis and explores its interactions within the CCR4-NOT complex that influence transcriptional and post-transcriptional regulation. Furthermore, we investigate the potential of CNOT2 as a biomarker and therapeutic target across various disease states, highlighting its significance in disease progression and treatment responsiveness. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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13 pages, 2281 KiB  
Article
Amphipathic Alpha-Helical Peptides AH1 and AH3 Facilitate Immunogenicity of Enhanced Green Fluorescence Protein in Rainbow Trout (Oncorhynchus mykiss)
by Kuan Chieh Peng and Ten-Tsao Wong
J. Mar. Sci. Eng. 2025, 13(8), 1497; https://doi.org/10.3390/jmse13081497 - 4 Aug 2025
Viewed by 63
Abstract
Vaccination is the most effective method to counteract infectious diseases in farmed fish. It secures aquaculture production and safeguards the wild stock and aquatic ecosystem from catastrophic contagious diseases. In vaccine development, recombinant subunit vaccines are favorable candidates since they can be economically [...] Read more.
Vaccination is the most effective method to counteract infectious diseases in farmed fish. It secures aquaculture production and safeguards the wild stock and aquatic ecosystem from catastrophic contagious diseases. In vaccine development, recombinant subunit vaccines are favorable candidates since they can be economically produced in large quantities without growing many pathogens, as in inactivated or attenuated vaccine production. However, recombinant subunit vaccines are often weak or deficient in immunogenicity, resulting in inadequate defenses against infections. Technologies that can increase the immunogenicity of recombinant subunit vaccines are in desperate need. Enhanced green fluorescence protein (EGFP) has a low antigenicity and is susceptible to folding changes and losing fluorescence after fusing with other proteins. Using these valuable features of EGFP, we comprehend two amphipathic alpha-helical peptides, AH1 and AH3, derived from Hepatitis C virus and Influenza A virus, respectively, that can induce high immune responses of their fused EGFP in fish without affecting their folding. AH3-EGFP has the most elevated cell binding, significantly 62% and 36% higher than EGFP and AH1-EGFP, respectively. Immunizations with AH1-EGFP or AH3-EGFP significantly induced higher anti-EGFP antibody levels 300–500-fold higher than EGFP immunization after the boost injection in rainbow trout. Our results suggest that AH1 and AH3 effectively increase the immunogenicity of EGFP without influencing its structure. Further validation of their value in other recombinant proteins is necessary to demonstrate their broader utility in enhancing the immunogenicity of subunit vaccines. We also suggest that EGFP and its variants are promising candidates for initially screening proper immunogenicity-enhancing peptides or proteins to advance recombinant subunit vaccine development. Full article
(This article belongs to the Section Marine Aquaculture)
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16 pages, 332 KiB  
Systematic Review
Blood Biomarkers as Optimization Tools for Computed Tomography in Mild Traumatic Brain Injury Management in Emergency Departments: A Systematic Review
by Ángela Caballero Ballesteros, María Isabel Alonso Gallardo and Juan Mora-Delgado
J. Pers. Med. 2025, 15(8), 350; https://doi.org/10.3390/jpm15080350 - 3 Aug 2025
Viewed by 80
Abstract
Background/Objectives: Traumatic brain injury (TBI), especially mild TBI (mTBI), is frequently caused by traffic accidents, falls, or sports injuries. Although computed tomography (CT) is the gold standard for diagnosis, overuse can lead to unnecessary radiation exposure, increased healthcare costs, and emergency department saturation. [...] Read more.
Background/Objectives: Traumatic brain injury (TBI), especially mild TBI (mTBI), is frequently caused by traffic accidents, falls, or sports injuries. Although computed tomography (CT) is the gold standard for diagnosis, overuse can lead to unnecessary radiation exposure, increased healthcare costs, and emergency department saturation. Blood-based biomarkers have emerged as potential tools to optimize CT scan use. This systematic review aims to evaluate recent evidence on the role of specific blood biomarkers in guiding CT decisions in patients with mTBI. Methods: A systematic search was conducted in the PubMed, Cochrane, and CINAHL databases for studies published between 2020 and 2024. Inclusion criteria focused on adult patients with mTBI evaluated using both CT imaging and at least one of the following biomarkers: glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and S100 calcium-binding protein B (S100B). After screening, six studies were included in the final review. Results: All included studies reported high sensitivity and negative predictive value for the selected biomarkers in detecting clinically relevant intracranial lesions. GFAP and UCH-L1, particularly in combination, consistently identified low-risk patients who could potentially forgo CT scans. While S100B also showed high sensitivity, discrepancies in cutoff values across studies highlighted the need for harmonization. Conclusions: Blood biomarkers such as GFAP, UCH-L1, and S100B demonstrate strong potential to reduce unnecessary CT imaging in mTBI by identifying patients at low risk of significant brain injury. Future research should focus on standardizing biomarker thresholds and validating protocols to support their integration into clinical practice guidelines. Full article
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19 pages, 4083 KiB  
Article
Multiplex CRISPR/Cas9 Editing of Rice Prolamin and GluA Glutelin Genes Reveals Subfamily-Specific Effects on Seed Protein Composition
by María H. Guzmán-López, Susana Sánchez-León, Miriam Marín-Sanz and Francisco Barro
Plants 2025, 14(15), 2355; https://doi.org/10.3390/plants14152355 - 31 Jul 2025
Viewed by 119
Abstract
Rice seed storage proteins (SSPs) play a critical role in determining the nutritional quality, cooking properties, and digestibility of rice. To enhance seed quality, CRISPR/Cas9 genome editing was applied to modify SSP composition by targeting genes encoding 13 kDa prolamins and type A [...] Read more.
Rice seed storage proteins (SSPs) play a critical role in determining the nutritional quality, cooking properties, and digestibility of rice. To enhance seed quality, CRISPR/Cas9 genome editing was applied to modify SSP composition by targeting genes encoding 13 kDa prolamins and type A glutelins. Three CRISPR/Cas9 constructs were designed: one specific to the 13 kDa prolamin subfamily and two targeting conserved GluA glutelin regions. Edited T0 and T1 lines were generated and analyzed using InDel analysis, SDS-PAGE, Bradford assay, and RP-HPLC. Insertions were more frequent than deletions, accounting for 56% and 74% of mutations in prolamin and glutelin genes, respectively. Editing efficiency varied between sgRNAs. All lines with altered protein profiles contained InDels in target genes. SDS-PAGE confirmed the absence or reduction in bands corresponding to 13 kDa prolamins or GluA subunits, showing consistent profiles among lines carrying the same construct. Quantification revealed significant shifts in SSP composition, including increased albumin and globulin content. Prolamin-deficient lines showed reduced prolamins, while GluA-deficient lines exhibited increased prolamins. Total protein content was significantly elevated in all edited lines, suggesting enrichment in lysine-rich fractions. These findings demonstrate that CRISPR/Cas9-mediated editing of SSP genes can effectively reconfigure the rice protein profile and enhance its nutritional value. Full article
(This article belongs to the Special Issue Advances and Applications of Genome Editing in Plants)
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37 pages, 2865 KiB  
Review
Ribosome Biogenesis and Function in Cancer: From Mechanisms to Therapy
by Kezia Gitareja, Shalini S. Chelliah, Elaine Sanij, Shahneen Sandhu, Jian Kang and Amit Khot
Cancers 2025, 17(15), 2534; https://doi.org/10.3390/cancers17152534 - 31 Jul 2025
Viewed by 388
Abstract
Ribosome biogenesis is a highly coordinated, multi-step process that assembles the ribosomal machinery responsible for translating mRNAs into proteins. It begins with the rate-limiting step of RNA polymerase I (Pol I) transcription of the 47S ribosomal RNA (rRNA) genes within a specialised nucleolar [...] Read more.
Ribosome biogenesis is a highly coordinated, multi-step process that assembles the ribosomal machinery responsible for translating mRNAs into proteins. It begins with the rate-limiting step of RNA polymerase I (Pol I) transcription of the 47S ribosomal RNA (rRNA) genes within a specialised nucleolar region in the nucleus, followed by rRNA processing, modification, and assembly with ribosomal proteins and the 5S rRNA produced by Pol III. The ribosomal subunits are then exported to the cytoplasm to form functional ribosomes. This process is tightly regulated by the PI3K/RAS/MYC oncogenic network, which is frequently deregulated in many cancers. As a result, ribosome synthesis, mRNA translation, and protein synthesis rates are increased. Growing evidence supports the notion that dysregulation of ribosome biogenesis and mRNA translation plays a pivotal role in the pathogenesis of cancer, positioning the ribosome as a promising therapeutic target. In this review, we summarise current understanding of dysregulated ribosome biogenesis and function in cancer, evaluate the clinical development of ribosome targeting therapies, and explore emerging targets for therapeutic intervention in this rapidly evolving field. Full article
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15 pages, 6331 KiB  
Article
Integrative Analysis of Iso-Seq and RNA-Seq Identifies Key Genes Related to Fatty Acid Biosynthesis and High-Altitude Stress Adaptation in Paeonia delavayi
by Qiongji He, Wenjue Yuan, Rui Wang, Wengao Yang, Guiqing He, Jinglong Cao, Yan Li, Lei Ye, Zhaoguang Li and Zhijiang Hou
Genes 2025, 16(8), 919; https://doi.org/10.3390/genes16080919 (registering DOI) - 30 Jul 2025
Viewed by 167
Abstract
Background/Objectives: Paeonia delavayi, a high-altitude-adapted medicinal and oil-producing plant, exhibits broad elevational distribution. Understanding how environmental factors regulate its growth across altitudes is critical for optimizing cultivation and exploiting its economic potential. Methods: In this study, we conducted a comprehensive Iso-Seq [...] Read more.
Background/Objectives: Paeonia delavayi, a high-altitude-adapted medicinal and oil-producing plant, exhibits broad elevational distribution. Understanding how environmental factors regulate its growth across altitudes is critical for optimizing cultivation and exploiting its economic potential. Methods: In this study, we conducted a comprehensive Iso-Seq and RNA-seq analysis to elucidate the transcriptional profile across diverse altitudes and three seed developmental stages. Results: Using Pacbio full-length cDNA sequencing, we identified 39,267 full-length transcripts, with 80.03% (31,426) achieving successful annotation. RNA-seq analysis uncovered 11,423 and 9565 differentially expressed genes (DEGs) in response to different altitude and developmental stages, respectively. KEGG analysis indicated that pathways linked to fatty acid metabolism were notably enriched during developmental stages. In contrast, pathways associated with amino acid and protein metabolism were significantly enriched under different altitudes. Furthermore, we identified 34 DEGs related to fatty acid biosynthesis, including genes encoding pivotal enzymes like biotin carboxylase, carboxyl transferase subunit alpha, malonyl-CoA-acyl carrier protein transacylase, 3-oxoacyl-ACP reductase, 3-hydroxyacyl-ACP dehydratase, and stearoyl-ACP desaturase enoyl-ACP reductase. Additionally, ten DEGs were pinpointed as potentially involved in high-altitude stress response. Conclusions: These findings provide insights into the molecular mechanisms of fatty acid biosynthesis and adaptation to high-altitude stress in peony seeds, providing a theoretical foundation for future breeding programs aimed at enhancing seed quality. Full article
(This article belongs to the Section Genes & Environments)
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13 pages, 1600 KiB  
Article
LIMK2-1 Is a Phosphorylation-Dependent Inhibitor of Protein Phosphatase-1 Catalytic Subunit and Myosin Phosphatase Holoenzyme
by Andrea Kiss, Emese Tóth, Zsófia Bodogán, Mohamad Mahfood, Zoltán Kónya and Ferenc Erdődi
Int. J. Mol. Sci. 2025, 26(15), 7347; https://doi.org/10.3390/ijms26157347 - 30 Jul 2025
Viewed by 173
Abstract
The C-kinase-activated protein phosphatase-1 (PP1) inhibitor of 17 kDa (CPI-17) is a specific inhibitor of the PP1 catalytic subunit (PP1c) and the myosin phosphatase (MP) holoenzyme. CPI-17 requires the phosphorylation of Thr38 in the peptide segment 35ARV(P)TVKYDRREL46 for inhibitory activity. CPI-17 [...] Read more.
The C-kinase-activated protein phosphatase-1 (PP1) inhibitor of 17 kDa (CPI-17) is a specific inhibitor of the PP1 catalytic subunit (PP1c) and the myosin phosphatase (MP) holoenzyme. CPI-17 requires the phosphorylation of Thr38 in the peptide segment 35ARV(P)TVKYDRREL46 for inhibitory activity. CPI-17 regulates myosin phosphorylation in smooth muscle contraction and the tumorigenic transformation of several cell lines via the inhibition of MP. A phosphospecific antibody (anti-CPI-17pThr38) against the phosphorylation peptide was used to determine the phosphorylation levels in cells. We found that phospho-CPI-17 and its closely related proteins are not present in HeLa and MCF7 cells after inducing phosphorylation by inhibiting phosphatases with calyculin A. In contrast, cross-reactions of proteins in the 40–220 kDa range with anti-CPI-17pThr38 were apparent. Searching the protein database for similarities to the CPI-17 phosphorylation sequence revealed several proteins with 42–75% sequence identities. The LIMK2-1 isoform emerged as a possible PP1 inhibitor. Experiments with Flag-LIMK2-1 overexpressed in tsA201 cells proved that LIMK2-1 interacts with PP1c isoforms and is phosphorylated predominantly by protein kinase C. Phosphorylated LIMK2-1 inhibits PP1c and the MP holoenzyme with similar potencies (IC50 ~28–47 nM). In conclusion, our results suggest that LIMK2-1 is a novel phosphorylation-dependent inhibitor of PP1c and MP and may function as a CPI-17-like phosphatase inhibitor in cells where CPI-17 is present but not phosphorylated upon phosphatase inhibition. Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in Macromolecules)
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14 pages, 1132 KiB  
Article
Phylogenetic Reclassification of Metarhizium granulomatis and Metarhizium viride Species Complex
by Johanna Würf and Volker Schmidt
Pathogens 2025, 14(8), 745; https://doi.org/10.3390/pathogens14080745 - 29 Jul 2025
Viewed by 255
Abstract
Metarhizium (M.) granulomatis and M. viride have previously been described as pathogens causing hyalohyphomycosis in various species of captive chameleons and bearded dragons (Pogona vitticeps). Previous studies yielded different genotypes of M. granulomatis and M. viride based on sequencing of the [...] Read more.
Metarhizium (M.) granulomatis and M. viride have previously been described as pathogens causing hyalohyphomycosis in various species of captive chameleons and bearded dragons (Pogona vitticeps). Previous studies yielded different genotypes of M. granulomatis and M. viride based on sequencing of the internal transcribed spacer 1-5.8S rDNA (ITS-1-5.8S) and a fragment of the large subunit of the 28S rDNA (LSU). The aim of this study was to clarify the relationships between these genotypes and obtain a more accurate phylogenetic classification by sequencing two different loci of the RNA polymerase II second largest subunit (NRPB2), referred to as RPB1 and RPB2, and the translation elongation factor 1 alpha (EF1α). A total of 23 frozen isolates from 21 lizards, including the first isolates of M. granulomatis and M. viride from Parson’s chameleons (Calumma parsonii), were available for phylogenetic analysis. A total of 13 isolates belonged to the M. granulomatis complex and 10 isolates belonged to the M. viride complex. Following the amplification and sequencing of the protein-coding genes, the resulting nucleotide sequences were analyzed, trimmed and assembled. These were further analyzed with regard to differences in single-nucleotide polymorphisms (SNPs) and amino acid structure. In consideration of the results of the present analyses, a phylogenetic reclassification is recommended. Three different genotypes of M. granulomatis can be distinguished, which can be phylogenetically addressed as subspecies. Six subspecies can be distinguished regarding M. viride. Full article
(This article belongs to the Special Issue Filamentous Fungal Pathogens: 2nd Edition)
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27 pages, 15511 KiB  
Review
Recent Advances in the Structural Studies of the Proteolytic ClpP/ClpX Molecular Machine
by Astrid Audibert, Jerome Boisbouvier and Annelise Vermot
Biomolecules 2025, 15(8), 1097; https://doi.org/10.3390/biom15081097 - 29 Jul 2025
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Abstract
AAA+ ATPases are ring-shaped hexameric protein complexes that operate as elaborate macromolecular motors, driving a variety of ATP-dependent cellular processes. AAA+ ATPases undergo large-scale conformational changes that lead to the conversion of chemical energy from ATP into mechanical work to perform a wide [...] Read more.
AAA+ ATPases are ring-shaped hexameric protein complexes that operate as elaborate macromolecular motors, driving a variety of ATP-dependent cellular processes. AAA+ ATPases undergo large-scale conformational changes that lead to the conversion of chemical energy from ATP into mechanical work to perform a wide range of functions, such as unfolding and translocation of the protein substrate inside a proteolysis chamber of an AAA+-associated protease. Despite extensive biochemical studies on these macromolecular assemblies, the mechanism of substrate unfolding and degradation has long remained elusive. Indeed, until recently, structural characterization of AAA+ protease complexes remained hampered by the size and complexity of the machinery, harboring multiple protein subunits acting together to process proteins to be degraded. Additionally, the major structural rearrangements involved in the mechanism of this complex represent a crucial challenge for structural biology. Here, we report the main advances in deciphering molecular details of the proteolytic reaction performed by AAA+ proteases, based on the remarkable progress in structural biology techniques. Particular emphasis is placed on the latest findings from high-resolution structural analysis of the ClpXP proteolytic complex, using crystallographic and cryo-EM investigations. In addition, this review presents some additional dynamic information obtained using solution-state NMR. This information provides molecular details that help to explain the protein degradation process by such molecular machines. Full article
(This article belongs to the Special Issue Structural Biology of Protein)
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