Biomolecules最新文献_第3页

Real-Time SPR Biosensing to Detect and Characterize Fast Dissociation Rate Binding Interactions Missed by Endpoint Detection and Implications for Off-Target Toxicity Screening. 实时SPR生物传感检测和表征端点检测错过的快速解离率结合相互作用和脱靶毒性筛选的意义。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-06-17 DOI: 10.3390/biom15060882

William Martelly, Rebecca L Cook, Chidozie Victor Agu, Lydia R Gushgari, Salvador Moreno, Sailaja Kesiraju, Mukilan Mohan, Bharath Takulapalli

{"title":"Real-Time SPR Biosensing to Detect and Characterize Fast Dissociation Rate Binding Interactions Missed by Endpoint Detection and Implications for Off-Target Toxicity Screening.","authors":"William Martelly, Rebecca L Cook, Chidozie Victor Agu, Lydia R Gushgari, Salvador Moreno, Sailaja Kesiraju, Mukilan Mohan, Bharath Takulapalli","doi":"10.3390/biom15060882","DOIUrl":"10.3390/biom15060882","url":null,"abstract":"Accurate detection of biomolecular interactions is essential in many areas, from the detection of the presence of biomarkers in the clinic to the development of therapeutic drugs and biologics in biopharma to the understanding of various biological processes in basic research. Traditional endpoint approaches can suffer from false-negative results for biomolecular interactions with fast kinetics. By contrast, real-time detection techniques like surface plasmon resonance (SPR) monitor interactions as they form and disassemble, reducing the risk of false-negative results. By leveraging cell-free expressed proteins captured on either glass or SPR biosensors and using two different commercial antibodies with variable off-rates that both target HaloTag antigens as a model, we compare and contrast results from a fluorescence endpoint assay versus real-time sensor-integrated proteome on chip (SPOC®) SPR-based detection. In this study, we illustrate the limitations of the representative immunofluorescent endpoint assay when investigating transient interactions characterized by fast dissociation rates. We highlight the importance of choosing reagents well suited to the selected assay, as well as the importance of considering binding kinetics and protein ligand conformational states when interpreting results from binding assays, especially for applications as critical as the off-target screening of therapeutics.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LncRNA-Protein Interactions: A Key to Deciphering LncRNA Mechanisms. LncRNA-蛋白相互作用：破译LncRNA机制的关键。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-06-17 DOI: 10.3390/biom15060881

Zuoneng Wang, Muhammad Aftab, Zigang Dong, Yanan Jiang, Kangdong Liu

{"title":"LncRNA-Protein Interactions: A Key to Deciphering LncRNA Mechanisms.","authors":"Zuoneng Wang, Muhammad Aftab, Zigang Dong, Yanan Jiang, Kangdong Liu","doi":"10.3390/biom15060881","DOIUrl":"10.3390/biom15060881","url":null,"abstract":"Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators in a multitude of biological processes. However, their functional basis, particularly structure-based functional characteristics, remains elusive. lncRNAs exert their influence primarily through intricate interactions with various cellular components. Among these, interactions with proteins have garnered increasing attention. Recent research highlights the significance of the interactions with proteins as a plausible mechanism underlying lncRNA functions. Here, we delve into the interactions between lncRNAs and RNA-binding proteins (RBPs), explore their implications in cellular processes, and examine bioinformatic and experimental approaches for characterizing these interactions. We introduce an innovative ISD strategy to decipher the mysterious mechanism of lncRNAs. Through reviewing the recent advances in the study of proteins and their complexes, we incorporate the ISD strategy into our integrated structural analysis pipeline for comprehensively understanding the structure-function relationship of lncRNAs. Advances in the development of innovative therapeutic approaches based on lncRNA-protein interactions (LPIs) are reviewed accordingly.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dairy Propionibacteria: Probiotic Properties and Their Molecular Bases. 乳制品丙酸菌：益生菌特性及其分子基础。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-06-17 DOI: 10.3390/biom15060886

Franca Rossi, Serena Santonicola, Valerio Giaccone, Alessandro Truant, Giampaolo Colavita

{"title":"Dairy Propionibacteria: Probiotic Properties and Their Molecular Bases.","authors":"Franca Rossi, Serena Santonicola, Valerio Giaccone, Alessandro Truant, Giampaolo Colavita","doi":"10.3390/biom15060886","DOIUrl":"10.3390/biom15060886","url":null,"abstract":"This review summarizes the current knowledge on the probiotic characteristics of dairy propionibacteria, represented by Propionibacterium freudenreichii and some Acidipropionibacterium species commonly consumed through raw milk cheese. For example, in Swiss-type cheeses, P. freudenreichii is added as a starter culture. Some strains of P. freudenreichii have been included in mixed probiotic commercial preparations or used to produce tablets from fermented culture media containing bioactive substances such as short-chain fatty acids (SCFAs), bifidogenic molecules, and vitamins. Acidipropionibacterium acidipropionici and A. jensenii strains have mainly been evaluated as health and productivity promoters in farm animals. For P. freudenreichii, the molecular mechanisms behind its probiotic action have been well elucidated, and recently, novel potential applications have been demonstrated in animal models. P. freudenreichii strains have been shown to mitigate inflammatory bowel diseases (IBDs) and mucositis and prevent necrotizing enterocolitis (NEC) in newborns. Their immunomodulation capacity has alleviated symptoms of food allergies, obesity, diabetes, colorectal cancer (CRC), and infections. Moreover, P. freudenreichii inhibited osteoclastogenesis in a rheumatoid arthritis model. Most observed effects are mediated by proteins on the cell surface or contained in extracellular vesicles (EVs) such as the surface layer (S-layer) protein SlpB, DlaT, and GroEL. No safety issues have been reported for these bacteria. However, investigations into transferable antibiotic resistance traits are still needed, and clinical trials are required to evaluate their effectiveness as probiotics for humans.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cardiac Glycosides: From Natural Defense Molecules to Emerging Therapeutic Agents. 心脏糖苷：从天然防御分子到新兴治疗剂。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-06-17 DOI: 10.3390/biom15060885

Arturo Ponce, Catalina Flores-Maldonado, Ruben G Contreras

{"title":"Cardiac Glycosides: From Natural Defense Molecules to Emerging Therapeutic Agents.","authors":"Arturo Ponce, Catalina Flores-Maldonado, Ruben G Contreras","doi":"10.3390/biom15060885","DOIUrl":"10.3390/biom15060885","url":null,"abstract":"Cardiac glycosides (CGs), a class of plant- and animal-derived compounds historically used to treat heart failure, have garnered renewed interest for their diverse pharmacological properties beyond Na+/K+-ATPase (NKA) inhibition. Recent studies reveal that CGs modulate key signaling pathways-such as NF-κB, PI3K/Akt, JAK/STAT, and MAPK-affecting processes central to cancer, viral infections, immune regulation, and neurodegeneration. In cancer, CGs induce multiple forms of regulated cell death, including apoptosis, ferroptosis, pyroptosis, and immunogenic cell death, while also inhibiting angiogenesis, epithelial-mesenchymal transition, and cell cycle progression. They demonstrate broad-spectrum antiviral activity by disrupting viral entry, replication, and mRNA processing in viruses such as HSV, HIV, influenza, and SARS-CoV-2. Immunologically, CGs regulate Th17 differentiation via RORγ signaling, although both inhibitory and agonistic effects have been reported. In the nervous system, CGs modulate neuroinflammation, support synaptic plasticity, and improve cognitive function in models of Alzheimer's disease, epilepsy, and multiple sclerosis. Despite their therapeutic potential, clinical translation is hindered by narrow therapeutic indices and systemic toxicity. Advances in drug design and nanocarrier-based delivery are critical to unlocking CGs' full potential as multi-target agents for complex diseases. This review synthesizes the current knowledge on the emerging roles of CGs and highlights strategies for their safe and effective repurposing.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Age Trajectories of O₂ Saturation and Levels of Serum Bicarbonate or End-Tidal CO₂ Across the Life Course of Women and Men: Insights from EHR and PSG Data. 男女生命历程中氧饱和度和血清碳酸氢盐或末潮CO2水平的年龄轨迹：来自EHR和PSG数据的见解

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-06-17 DOI: 10.3390/biom15060884

Leping Li, Min Shi, David M Umbach, Zheng Fan

{"title":"Age Trajectories of O2 Saturation and Levels of Serum Bicarbonate or End-Tidal CO2 Across the Life Course of Women and Men: Insights from EHR and PSG Data.","authors":"Leping Li, Min Shi, David M Umbach, Zheng Fan","doi":"10.3390/biom15060884","DOIUrl":"10.3390/biom15060884","url":null,"abstract":"To elucidate the changes in gas exchange across the life course, we estimated the age trajectories of O2 saturation, CO2 (as either end-tidal or serum bicarbonate), resting heart rate, and resting respiratory rate from age 2 yr onward in female and male patients separately. We utilized two sources' data: electronic health records (EHR) representing ambulatory visits of approximately 53,000 individuals and sleep clinic polysomnogram (PSG) records representing an additional ~21,000. We used linear regression to estimate age-group-specific mean response levels for women and men. We compared estimated female-male differences between pre- and post-pubertal children and between pre- and post-menopausal periods among adults. Women between 15 and 45 years had higher O2 saturation and lower serum bicarbonate levels or end-tidal CO2 levels than men of similar ages. For O2 saturation and for both measures of CO2, the female-male difference was larger on average among adults at pre-menopausal ages than those at post-menopausal ages. Women had higher O2 saturation throughout their lives than men; however, the difference disappeared in the elderly. Women between menarche and menopause had significantly lower end-tidal CO2 and serum bicarbonate than men of similar ages. After menopause, however, women appeared to have higher mean levels of both end-tidal CO2 and serum bicarbonate than men.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Analysis of Novel DNA Adducts Derived from Acetaldehyde. 乙醛衍生的新型DNA加合物分析。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-06-16 DOI: 10.3390/biom15060878

Yuuki Betsuyaku, Mina Motohashi, Akira Sassa, Takeji Takamura-Enya, Yukari Totsuka

{"title":"Analysis of Novel DNA Adducts Derived from Acetaldehyde.","authors":"Yuuki Betsuyaku, Mina Motohashi, Akira Sassa, Takeji Takamura-Enya, Yukari Totsuka","doi":"10.3390/biom15060878","DOIUrl":"10.3390/biom15060878","url":null,"abstract":"Alcohol consumption is a known risk factor for esophageal and liver cancers. Recently, it was reported that mutation signatures characterized by T:A to C:G mutations (SBS16), which are suggested to be associated with alcohol intake, are frequently detected in esophageal, liver, and stomach cancers among the Japanese population. However, the scientific evidence linking alcohol consumption to SBS16 remains lacking. Acetaldehyde (AA), a carcinogenic metabolite of alcohol, is considered a key contributor to alcohol-related cancer development. Although the guanine adducts associated with alcohol exposure have been reported as part of its carcinogenic mechanism, an adenine adduct, N6-ethyl-deoxyadenosine (N6-ethyl-dA), a potential contributor to the SBS16 mutation pattern, was recently identified using a mass spectrometry-based DNA adductome approach. However, the mutagenicity assessment of N6-ethyl-dA using primer extension assays and the supF gene mutation test showed that this adenine adduct is not mutagenic. To identify another candidate as a driver adduct for SBS16, a DNA adductome approach was conducted, leading to the identification of a novel adenine adduct, 3-(2'-deoxyribos-1'-yl)-7,9-dimethyl-3,9-dihydro-7H-[1,3,5]oxadiazino[4,3-i]purine (N1-oxydiethylidene-dA), in which two AA molecules are bound to an adenine base. Moreover, N1-oxydiethylidene-dA was detected in mouse livers, and its levels increased following ethanol administration, suggesting that alcohol may contribute to SBS16 induction via the formation of N1-oxydiethylidene-dA.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Analytical and Clinical Validation of a Plasma Fibroblast Growth Factor 21 ELISA Kit Using an Automated Platform in Steatotic Liver Disease. 血浆成纤维细胞生长因子21酶联免疫吸附测定试剂盒在脂肪肝疾病中的分析和临床验证

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-06-16 DOI: 10.3390/biom15060877

Makito Tanaka, Shingo Tanaka, Ryo Kobayashi, Ryosei Murai, Satoshi Takahashi

{"title":"Analytical and Clinical Validation of a Plasma Fibroblast Growth Factor 21 ELISA Kit Using an Automated Platform in Steatotic Liver Disease.","authors":"Makito Tanaka, Shingo Tanaka, Ryo Kobayashi, Ryosei Murai, Satoshi Takahashi","doi":"10.3390/biom15060877","DOIUrl":"10.3390/biom15060877","url":null,"abstract":"Steatotic liver disease is a global health challenge that requires reliable and noninvasive diagnostic biomarkers. This research aimed to validate the analytical and clinical performance of a fibroblast growth factor 21 (FGF21) enzyme-linked immunosorbent assay (ELISA) kit using an automated immunoassay analyzer. Plasma FGF21 levels were measured using a commercial ELISA kit on an automated immunoassay analyzer. Validation included intra- and inter-assay precision, dilution linearity, spike recovery, lower limit of quantification (LLOQ), interference testing, and sample stability analysis. Clinical evaluation involved 97 patients who underwent abdominal ultrasound-based attenuation imaging for the diagnosis of hepatic steatosis. The assay demonstrated high analytical precision, with intra- and inter-assay coefficients of variation <15% and an LLOQ of 3.260 pg/mL. Dilution linearity, spike recovery, and interference tests confirmed the reliability of the assay, whereas stability tests highlighted the minimal effect of freeze-thaw cycles and storage conditions. Clinically, FGF21 levels correlated with attenuation coefficient (r = 0.44). Diagnostic performance indicated 84% sensitivity and 81% specificity at defined FGF21 thresholds for the diagnosis of hepatic steatosis. This research confirmed the reliable analytical and clinical performance of the FGF21 ELISA kit, reinforcing its potential as a diagnostic biomarker of hepatic steatosis.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

New Insights into the Sex Chromosome Evolution of the Common Barker Frog Species Complex (Anura, Leptodactylidae) Inferred from Its Satellite DNA Content. 从卫星DNA含量推断普通吠蛙物种复合体（无尾目，细趾蛙科）性染色体进化的新见解。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-06-16 DOI: 10.3390/biom15060876

Lucas H B Souza, Juan M Ferro, Helena M Milanez, Célio F B Haddad, Luciana B Lourenço

{"title":"New Insights into the Sex Chromosome Evolution of the Common Barker Frog Species Complex (Anura, Leptodactylidae) Inferred from Its Satellite DNA Content.","authors":"Lucas H B Souza, Juan M Ferro, Helena M Milanez, Célio F B Haddad, Luciana B Lourenço","doi":"10.3390/biom15060876","DOIUrl":"10.3390/biom15060876","url":null,"abstract":"Satellite DNAs (satDNAs) play a crucial role in understanding chromosomal evolution and the differentiation of sex chromosomes across diverse taxa, particularly when high karyotypic diversity occurs. The Physalaemus cuvieri-Physalaemus ephippifer species complex comprises at least seven divergent lineages, each exhibiting specific karyotypic signatures. The group composed of Ph. ephippifer, Lineage 1B of 'Ph. cuvieri' (L1B), and a lineage resulting from their secondary contact is especially intriguing due to varying degrees of sex chromosome heteromorphism. In this study, we characterized the satellitome of Ph. ephippifer in order to identify novel satDNAs that may provide insights into chromosomal evolution, particularly concerning sex chromosomes. We identified 62 satDNAs in Ph. ephippifer, collectively accounting for approximately 10% of the genome. Notably, nine satDNA families were shared with species from distantly related clades, raising questions about their potential roles in anurans genomes. Among the seven satDNAs mapped via fluorescent in situ hybridization, PepSat3 emerged as a strong candidate for the centromeric sequence in this group. Additionally, PepSat11 and PepSat24 provided evidence supporting a translocation involving both arms of the W chromosome in Ph. ephippifer. Furthermore, a syntenic block composed of PepSat3, PcP190, and PepSat11 suggested an inversion event during the divergence of Ph. ephippifer and L1B. The variation in signal patterns of satDNAs associated with nucleolar organizer regions (NORs) highlights the complexity of NOR evolution in this species complex, which exhibits substantial diversity in this genomic region. Additionally, our findings for PepSat30-350 emphasize the importance of validating the sex-biased abundance of satDNAs.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Not Just PA28γ: What We Know About the Role of PA28αβ in Carcinogenesis. 不仅仅是PA28γ：我们对PA28αβ在癌变中的作用的了解

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-06-16 DOI: 10.3390/biom15060880

Paolo Cascio

{"title":"Not Just PA28γ: What We Know About the Role of PA28αβ in Carcinogenesis.","authors":"Paolo Cascio","doi":"10.3390/biom15060880","DOIUrl":"10.3390/biom15060880","url":null,"abstract":"The ubiquitin-proteasome pathway performs a strictly controlled degradation of specific protein substrates within the eukaryotic cell. This catabolic mechanism allows the rapid removal of proteins damaged in any way, and therefore potentially capable of compromising cellular homeostasis, as well as the constant turnover of all cellular proteins, in order to balance their synthesis and thus maintain the correct levels of proteins required by the cell at any given time. Consequently, the ubiquitin-proteasome system plays a fundamental role in regulating essential cellular processes, such as the cell cycle, apoptosis, immune responses, and inflammation, whose dysregulation or malfunction can lead to neoplastic transformation. Not surprisingly, therefore, alterations in the activity and regulatory mechanisms of the proteasome are common not only in various types of tumors, but often represent a contributing cause of oncogenesis itself. Among proteasome modulators, PA28γ, due to its function in promoting cell growth and proliferation, while inhibiting apoptosis and cell-mediated immune responses, has received great attention in recent years for its well established pro-tumoral activity. Conversely, the role played in oncogenesis by the second paralogue of the PA28 family of proteasome activators, namely PA28αβ, is less clearly defined, which is also related to the lower level of general understanding of its cellular activities and biological functions. However, increasing experimental evidence has demonstrated that PA28αβ also plays a non-secondary role in the process of neoplastic transformation and tumor growth, both by virtue of its regulatory function on class I cell-mediated immune responses and through activity promoting cell duplication and growth. This review aims to summarize the current knowledge and evidence on the molecular mechanisms and cellular functions through which PA28αβ may support development and growth of cancer.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SLC4A11 Revisited: Isoforms, Expression, Functions, and Unresolved Questions. SLC4A11重访：异构体，表达，功能和未解决的问题。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-06-16 DOI: 10.3390/biom15060875

Polina Alekseevna Kovaleva, Elena Sergeevna Kotova, Elena Ivanovna Sharova, Liubov Olegovna Skorodumova

{"title":"SLC4A11 Revisited: Isoforms, Expression, Functions, and Unresolved Questions.","authors":"Polina Alekseevna Kovaleva, Elena Sergeevna Kotova, Elena Ivanovna Sharova, Liubov Olegovna Skorodumova","doi":"10.3390/biom15060875","DOIUrl":"10.3390/biom15060875","url":null,"abstract":"The SLC4A11 gene encodes a membrane transporter implicated in congenital hereditary endothelial dystrophy, Harboyan syndrome, and certain cancers. Despite its clinical importance, current data on SLC4A11 expression patterns, transcript variants, and functional roles remain inconsistent and sometimes contradictory. We have systematized existing data, identified areas of consensus, and highlighted discrepancies. This review addresses SLC4A11 transcript and isoform diversity and how this complexity influences both the interpretation of its tissue expression patterns (particularly in the corneal endothelium) and the investigation of its functional roles in health and disease. Our review also untangles the evolving understanding of SLC4A11 function, from its initial classification as a bicarbonate transporter to its established roles in NH3- and pH-regulated H+/OH- transport, lactate efflux, cellular stress responses, and adhesion. The review details how pathogenic mutations disrupt protein maturation, membrane localization, or transport activity, contributing to corneal fluid imbalance and disease. We also discuss the emerging role of SLC4A11 in cancer metabolism and the common metabolic features of dystrophic corneas and tumors. Methodological challenges are appraised, encouraging caution in interpretation and the need for isoform-specific studies. Overall, this review provides a comprehensive update on SLC4A11 biology and identifies key gaps for future research.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0