Biochimica Et Biophysica Acta[JOURNAL]
Sun
200 papers
Complex anionic and zwitterionic N-glycans in Drosophila melanogaster.
Maďarová K, Dutkiewicz Z, Nuschy L … +5 more , John MM, Wang H, Eckmair B, Wilson IBH, Paschinger K
Biochim Biophys Acta Gen Subj · 2026 Aug · PMID 42107810 · Publisher ↗
Drosophila melanogaster is arguably the most widely-employed invertebrate model organism; here we have focussed on its anionic N-glycome applying our off-line HPLC-MALDI-TOF-MS approach. Using MS/MS in combination with c...
Drosophila melanogaster is arguably the most widely-employed invertebrate model organism; here we have focussed on its anionic N-glycome applying our off-line HPLC-MALDI-TOF-MS approach. Using MS/MS in combination with chemical and enzymatic treatments, we reveal not only sulphated and glucuronylated N-glycans further to those previously proposed, but demonstrate that this dipteran insect modifies some structures with phosphoethanolamine, a zwitterion. Although not as complex as some other insect N-glycomes, N-glycans with up to three antennae can feature also LacdiNAc or β1,3-galactosylation as the basis for anionic modifications, whereby some glycans also carry up to five anionic/zwitterionic moieties; in total approximately 180 N-linked oligosaccharide structures, including isomers and isobars, can be proposed. A prototype microarray based on fractionated N-glycans was printed and showed different fucose-specific lectin binding to N-glycans from a wild-type and a fucose-deficient strain, whereas serum amyloid P bound anionic glycans. In terms of enzymatic analyses, recombinant forms of both N-acetylglucosaminyltransferases II and IV were expressed and their activities correlate with the occurrence of up to three antennae on Drosophila N-glycans. Overall, in keeping with the accepted phylogeny, the fruit fly is indeed closest in glycomic terms to mosquitoes, but also shares the feature of phosphoethanolamine modifications with the honeybee, rather than the phosphorylcholine found in lepidopteran species. Nevertheless, there are many unanswered questions regarding N-glycosylation in Drosophila; a mix of genomic, biochemical and glycomic approaches will be required to solve the biosynthesis and functions of this key set of post-translational modifications in this and other insects.
Raman spectroscopic characterization of protein changes induced by 5-fluorouracil in colon cancer cells.
Kopeć M, Beton-Mysur K, Sroka-Bartnicka A … +1 more , Brożek-Płuska B
Biochim Biophys Acta Mol Basis Dis · 2026 Aug · PMID 42107809 · Publisher ↗
This paper aims to evaluate the current state of knowledge on understanding the impact of cytostatic on colon cancer progression. We have compared the Raman profile of the normal colon fibroblast cell line (CCD-18Co) and...
This paper aims to evaluate the current state of knowledge on understanding the impact of cytostatic on colon cancer progression. We have compared the Raman profile of the normal colon fibroblast cell line (CCD-18Co) and two colon epithelial cancer cell lines (Caco-2 and LoVo). Our results indicate that ratios 1656/1305, 1256/1305, and 1656/1256 are the most relative Raman biomarkers for discrimination between normal fibroblast and cancer epithelial colon cells. The study results demonstrate that metabolic pathway reprogramming induced by 5-fluorouracil (5-FU) during colon cancer progression is detectable within both the whole cell and individual cell substructures, such as nucleus. These findings suggest that 5-FU-associated metabolic changes directly impact nuclear functions, which are critical for mechanisms of resistance and disease advancement. In the presented studies, the analysis of the secondary structure of proteins has also been performed. The obtained results demonstrate that CCD18-Co-CTRL and Lovo+5-FU (100 μM) cells are dominated by α-helix protein structure. Moreover, the obtained results indicate that supplementation with 5-fluorouracil (5-FU) may reduce the structural features associated with β-sheet-rich proteins.
Extracellular vesicles in tumor immune escape and therapeutic resistance: mechanisms and immunopharmacological opportunities.
Xiao Z, Luo Z, Chen L … +1 more , Qu S
Biochim Biophys Acta Mol Basis Dis · 2026 Aug · PMID 42107808 · Publisher ↗
Extracellular vesicles (EVs) are key mediators of intercellular communication in cancer. In this review, we focus on how EVs mechanistically link tumor immune escape with therapeutic resistance and how these insights may...
Extracellular vesicles (EVs) are key mediators of intercellular communication in cancer. In this review, we focus on how EVs mechanistically link tumor immune escape with therapeutic resistance and how these insights may be translated into immunopharmacological opportunities. Tumor-derived EVs remodel the tumor microenvironment by suppressing antitumor immunity, promoting regulatory immune phenotypes, and facilitating resistance to chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Conversely, selected immune cell-derived EVs and engineered EV platforms show therapeutic potential for immune modulation and targeted drug delivery. We further discuss major translational challenges, including EV heterogeneity, incomplete standardization of isolation and characterization, limited large-scale production, and insufficient in vivo biodistribution assessment. Overall, EVs represent both pathogenic mediators and promising therapeutic tools, and a deeper mechanistic understanding may support the development of more clinically translatable EV-directed cancer strategies.
Coordinated regulation of cell differentiation by sphingosine-1-phosphate receptors in renal epithelial cells.
Romero DJ, Pescio LG, Loiacono G … +6 more , Palavecino AN, Fernández FE, Alvarez MB, Santacreu BJ, Guaytima EDV, Favale NO
Biochim Biophys Acta Mol Cell Res · 2026 Jun · PMID 42107720 · Publisher ↗
Sphingolipids regulate essential cellular processes, with sphingosine-1-phosphate (S1P) emerging as a critical modulator of proliferation, migration, and differentiation. While intracellular S1P governs sphingolipid meta...
Sphingolipids regulate essential cellular processes, with sphingosine-1-phosphate (S1P) emerging as a critical modulator of proliferation, migration, and differentiation. While intracellular S1P governs sphingolipid metabolism during renal epithelial differentiation, its role as a ligand for S1P receptors (S1PRs) remains poorly understood. Here, we investigated the roles of S1PR1, S1PR2, and S1PR3 during the differentiation of Madin-Darby canine kidney (MDCK) cells. We found that S1PR2 and S1PR3 are critical for apical membrane formation, while S1PR2 additionally regulates adherens junction (AJ) maturation and actin cytoskeleton reorganization, essential for a differentiated epithelial morphology. Functional assays, including pharmacological inhibition and genetic silencing, showed that inhibition of S1PR2 impaired AJ formation and disrupted epithelial differentiation. Notably, S1PR2 restoration re-established AJ formation and epithelial organization, which underscores its critical role in maintaining cell-cell adhesion. Interestingly, S1PR2 exhibited distinct localization patterns throughout the differentiation process, transitioning from predominantly intracellular structures in proliferating cells to a more discrete peripheral/plasma membrane distribution along cell-cell boundaries in differentiated cells. These findings provide new insights into the spatial regulation of S1P signaling during renal epithelial differentiation and highlighted the emerging role of S1PR signaling in epithelial cell organization. This work broadens our understanding of S1PR2 mechanisms and suggests differential roles across stages of epithelial differentiation, thus offering potential therapeutic strategies for conditions involving renal epithelial dysfunction.
Remodeling the pancreatic tumor microenvironment by chemotherapy: New opportunities for combination therapy.
Tang Y, Luo X, Zhou F … +5 more , Gu J, Li X, Yang G, Zhang T, You L
Biochim Biophys Acta Rev Cancer · 2026 May · PMID 42107558 · Publisher ↗
The incidence and mortality of pancreatic ductal adenocarcinoma (PDAC) have risen steadily, yet the five-year survival rate remains a dismal 9%, underscoring the urgent need for novel therapeutic strategies. While immuno...
The incidence and mortality of pancreatic ductal adenocarcinoma (PDAC) have risen steadily, yet the five-year survival rate remains a dismal 9%, underscoring the urgent need for novel therapeutic strategies. While immunotherapy has shown remarkable efficacy across multiple cancer types, it has largely failed to demonstrate meaningful clinical benefit as a monotherapy in PDAC. Emerging evidence indicates that combining chemotherapy with immunotherapy improves overall survival, suggesting that chemotherapy exerts meaningful modulatory effects on the PDAC tumor microenvironment (TME) that may enhance immunotherapy responsiveness. This review systematically characterizes the immunosuppressive and stromal features of the PDAC TME, delineates the multifaceted effects of chemotherapy on TME remodeling, and identifies potential combinatorial targets that may synergize with chemotherapy to improve therapeutic outcomes.
Anoikis resistance as a key driver of glioma malignancy: From ECM detachment to potential druggable targets.
Zou Y, Zou C, Huang X … +2 more , Zhu Y, Wang Q
Biochim Biophys Acta Rev Cancer · 2026 May · PMID 42107557 · Publisher ↗
Gliomas, particularly glioblastoma multiforme (GBM), represent the most predominant and aggressive primary central nervous system (CNS) tumors, with treatment challenges stemming from their invasiveness and high recurren...
Gliomas, particularly glioblastoma multiforme (GBM), represent the most predominant and aggressive primary central nervous system (CNS) tumors, with treatment challenges stemming from their invasiveness and high recurrence. Anoikis is a form of programmed cell death triggered by detachment from the extracellular matrix. Normal cells typically undergo self-elimination, while glioma and other cancer cells often subvert this process through acquired anoikis resistance, enabling sustained anchorage-independent survival and proliferation. This resistance is a key driver of invasion, metastasis, and recurrence. Here, we outline recent advances in morphological and ultrastructural modifications, molecular, and signaling mechanisms governing anoikis and its resistance in malignant cells, with a focus on their specific pathophysiological role in glioma pathogenesis and progression. The experimental platforms are also discussed. Furthermore, we summarize emerging therapeutic strategies targeting anoikis resistance to provide a framework for understanding its contribution to glioma stem cell (GSC) origination, invasion and metastasis, treatment resistance, and recurrence, thereby informing novel therapeutic strategies for GBM and other cancers.
The role and therapeutic potential of protein glycosylation in the immune regulation of breast cancer.
Huang C, Liu H, Ming J
Biochim Biophys Acta Rev Cancer · 2026 May · PMID 42107556 · Publisher ↗
Breast cancer has emerged as the most prevalent malignant tumor among women worldwide. Its intricate and highly heterogeneous pathogenesis presents substantial challenges for effective treatment. In recent years, the inc...
Breast cancer has emerged as the most prevalent malignant tumor among women worldwide. Its intricate and highly heterogeneous pathogenesis presents substantial challenges for effective treatment. In recent years, the increasing prominence of tumor immunotherapy has highlighted the pivotal role of protein glycosylation, particularly its regulation of glycan structural alterations in the initiation, progression, and immune evasion mechanisms of breast cancer. Evidence suggests that glycan modifications-such as N-glycosylation, O-glycosylation, fucosylation, and sialylation-not only significantly influence tumor cell biology but also directly modulate the function and stability of key immune checkpoint molecules, including PD-1/PD-L1, CD24, and members of the B7 family. Aberrant glycosylation in breast cancer cells fosters the establishment of an immunosuppressive microenvironment, a critical factor that limits the efficacy of immunotherapy. Consequently, interventions targeting glycosylation modifications present promising strategies to enhance the therapeutic response to immunotherapy in breast cancer patients. Thus, our comprehensive exploration of the underlying mechanisms of glycosylation modifications in breast cancer immunotherapy provides a robust theoretical foundation and identifies novel intervention targets to overcome the therapeutic challenges faced in breast cancer and other immunologically "cold" tumors.
Bibliometric analysis of the association between asthma and cancer: Mechanistic insights and directions for clinical translation.
Deng B, Guan R, Li G … +1 more , Yang W
Biochim Biophys Acta Rev Cancer · 2026 May · PMID 42107555 · Publisher ↗
This bibliometric analysis maps the global research landscape on asthma-cancer associations (2000-2025) using 378 publications. The field is led by the United States (36%) and China (22%), with keyword co-occurrence reve...
This bibliometric analysis maps the global research landscape on asthma-cancer associations (2000-2025) using 378 publications. The field is led by the United States (36%) and China (22%), with keyword co-occurrence revealing four research axes: pulmonary disease links, chronic inflammation, allergy-immunity pathways, and notably underdeveloped molecular mechanism studies. We address the central "asthma paradox"-contradictory reports of asthma as a risk, protective, or neutral factor for various cancers-by synthesizing mechanistic hypotheses. A key insight is the dynamic balance between cancer-promoting and -suppressing forces. For example, TGF-β exhibits dose-dependent duality: tumor-suppressive at low levels, but promoting immune evasion and metastasis at high concentrations characterized by severe neutrophilic asthma. Drug repurposing candidates (e.g., montelukast, ciclesonide) show anti-proliferative activity, confirming shared pathogenic pathways. We identify two primary sources of inconsistency: uncontrolled confounders (e.g., smoking) and, critically, the failure to account for asthma heterogeneity. Th2-high (allergic) and Th2-low (non-allergic/neutrophilic) endotypes likely exert divergent effects on cancer risk and progression. Current research remains predominantly epidemiological (53.5%), with mechanistic studies (16.1%) limited by these factors. To advance from associative observations to causal understanding, the study calls for future research to adopt a precision medicine framework. This includes stratifying patients by asthma endotype in large, prospective cohorts and integrating single-cell multi-omics, Mendelian randomization, and real-world data to elucidate the context-dependent molecular mechanisms, such as the dual role of TGF-β, and to validate promising drug repurposing candidates like montelukast.
Reprogramming regulatory T cell plasticity for cancer immunotherapy.
Issa ME, Schcolnik-Cabrera A, Monetta R
Biochim Biophys Acta Rev Cancer · 2026 May · PMID 42107554 · Publisher ↗
Regulatory T cells (Tregs) maintain immune homeostasis by suppressing excessive immune responses. In the context of cancer, Tregs are abundantly recruited to inhibit immunity against tumoral cells, facilitate immune evas...
Regulatory T cells (Tregs) maintain immune homeostasis by suppressing excessive immune responses. In the context of cancer, Tregs are abundantly recruited to inhibit immunity against tumoral cells, facilitate immune evasion, and promote tumor progression. While Treg depletion strategies have repeatedly failed in the clinic due to severe autoimmune side effects, lack of specificity, and rapid compensatory recruitment, a critical unmet need remains for safer and more effective approaches. Emerging evidence highlights the remarkable plasticity of Tregs, allowing them to adopt an inflammatory phenotype in response to tumor-associated cytokines. Thus, leveraging this plasticity, rather than attempting broad depletion, may represent a superior anticancer strategy. This plasticity is marked by the expression of transcription factors like T-bet (Th1-like) and RORγt (Th17-like), the production of pro-inflammatory cytokines such as IFN-γ and IL-17, and even the acquisition of differential energetic preferences pertaining to glucose or glutamine. These changes can weaken Treg suppressive functions or paradoxically enhance inflammation in the tumor microenvironment, thereby creating a complex interplay between immune suppression and anti-tumor effector activity. Understanding the molecular cues driving Treg plasticity is therefore critical for designing novel therapies that shift Tregs toward an effector-like state, ultimately enhancing anti-tumor immunity and improving the efficacy of current immunotherapies. This review offers a fresh perspective on how Treg plasticity can be therapeutically harnessed to overcome the persistent limitations of conventional Treg-targeted approaches.
Heparin interactions with phospholipid and cholesterol monolayers mimicking SARS-CoV-2 envelope and host membranes: A Langmuir film approach.
Pantarotto PV, Dos Santos KF, Silva ALT … +2 more , Nader HB, Caseli L
Biochim Biophys Acta Biomembr · 2026 Jul · PMID 42106139 · Publisher ↗
Understanding how heparin modulates membrane interactions relevant to SARS-CoV-2 entry is essential for elucidating its antiviral mechanisms. Here, Langmuir monolayers were used as biomimetic models of viral and host mem...
Understanding how heparin modulates membrane interactions relevant to SARS-CoV-2 entry is essential for elucidating its antiviral mechanisms. Here, Langmuir monolayers were used as biomimetic models of viral and host membranes to investigate interactions with the spike receptor-binding domain (RBD), ACE2, and heparin. Surface pressure-area isotherms, dilatational rheology, Brewster angle microscopy, and PM-IRRAS revealed lipid-dependent effects. In viral-model monolayers, RBD and heparin significantly disrupted film organization, decreasing elasticity and increasing dissipative behavior, with the RBD-heparin complex producing the most pronounced fluidization despite increased local chain order. In host-model monolayers, ACE2 was the main perturbing agent, while heparin primarily interacted with ACE2 without major additional disruption; subsequent RBD addition induced moderate structural reorganization. Notably, opposing trends between compressional and dynamic moduli highlight distinct relaxation regimes governing interfacial mechanics. Overall, heparin acts as a membrane-active modulator, altering interfacial organization and mechanics in a lipid-dependent manner. These findings suggest that, beyond direct protein binding, heparin may interfere with SARS-CoV-2 infection through membrane-mediated mechanisms.
Curcumin suppresses HNSCC tumorigenesis through directly targeting FOSL1/JUN.
Li J, Pandit S, Manupati K … +3 more , Wang A, Zaman SU, Cen Y
Biochim Biophys Acta Mol Basis Dis · 2026 Aug · PMID 42106013 · Publisher ↗
Natural products and affordable herbal medications have emerged as promising alternatives for cancer therapy, particularly for patients with limited access to standard treatments. Among these, curcumin, the bioactive pol...
Natural products and affordable herbal medications have emerged as promising alternatives for cancer therapy, particularly for patients with limited access to standard treatments. Among these, curcumin, the bioactive polyphenol from Curcuma longa (turmeric), has shown broad anti-cancer potential. However, its molecular mechanism remains poorly defined, especially for head and neck squamous cell carcinoma (HNSCC). Here, we identify curcumin as a potent inhibitor of HNSCC tumorigenesis and explored its underlying mechanism. Comparative analyses of three anti-cancer natural products, including curcumin, gingerol, and allicin, revealed that only curcumin robustly inhibited HNSCC cell proliferation, invasion, and cancer stem cell self-renewal, with potency comparable or superior to cisplatin. Transcriptomic and Gene Set Enrichment Analyses demonstrated that curcumin significantly suppressed FOSL1/AP-1 signaling, a well-known key oncogenic signaling that promotes malignant progression of HNSCC. Biophysical and biochemical assays showed that curcumin directly binds to the FOSL1/JUN heterodimer (Kd ≈ 10 μM), disrupting its DNA-binding activity. In agree with this finding, chromatin immunoprecipitation confirmed that curcumin inhibited FOSL1/JUN recruitment to promoter of cancer stem cell marker gene BMI1, as well as super-enhancer-associated oncogenic loci such as MET, EGFR and TP63. At last, curcumin treatment profoundly suppressed HNSCC tumor growth in xenograft model and exhibited superior efficacy compared with the FOSL1/AP-1 inhibitor T-5224, without apparent toxicity. Collectively, our findings identify FOSL1/JUN complex as a direct molecular target of curcumin and uncover a novel mechanism by which this accessible natural product suppresses HNSCC tumorigenesis, supporting its potential as an affordable and safe therapeutic option for cancer treatment.
Structure and biosynthetic mechanisms of galactomannans in filamentous fungi.
Oka T, Kadooka C, Tanaka Y … +1 more , Hira D
Biochim Biophys Acta Gen Subj · 2026 Aug · PMID 42105885 · Publisher ↗
The cell wall of filamentous fungi is crucial for the physical protection of the cell, the sensing environmental cues, and the expression of virulence. The fungal cell wall consists of a rigid yet flexible three-dimensio...
The cell wall of filamentous fungi is crucial for the physical protection of the cell, the sensing environmental cues, and the expression of virulence. The fungal cell wall consists of a rigid yet flexible three-dimensional network in which structural polysaccharides, such as β-(1 → 3)-glucan and chitin, are intricately intertwined with α-(1 → 3)-glucan, galactosaminogalactan, and galactomannan. Galactomannan is a glycan containing mannose and galactofuranose, the latter of which is a sugar residue absent in humans, and it serves as an important indicator in the clinical diagnosis of invasive pulmonary aspergillosis. Moreover, the biosynthetic pathway of galactomannan is a potential target for novel antifungal drugs. The term galactomannan does not refer to a single molecule but is rather a collective term for structurally distinct fungal-type and O-mannose-type galactomannans. The specific enzymes and precise pathways responsible for the biosynthesis of these glycans have long remained elusive. In this review, we present the current understanding of the supply and transport pathways of sugar nucleotides that are the foundation of galactomannan biosynthesis and describe the functions and three-dimensional protein structures of the key glycosyltransferases responsible for synthesizing fungal-type and O-mannose-type galactomannans, with a focus on our recent discoveries. We also introduce recent findings regarding newly discovered conidia-specific mannan structures and mycelial N-glycan outer chain-like mannan structures. Together, these insights provide future perspectives regarding the development of novel antifungal agents.
Unveiling NDRGs as potential modulators of insulin signaling and insulin resistance in the central nervous system.
Mukherjee A, Dey CS
Biochim Biophys Acta Mol Cell Res · 2026 Jun · PMID 42105872 · Publisher ↗
The N-myc downstream-regulated gene (NDRG) family comprises four proteins (NDRG1-4) that lack intrinsic catalytic activity and participate in diverse cellular processes, including differentiation, stress responses, and m...
The N-myc downstream-regulated gene (NDRG) family comprises four proteins (NDRG1-4) that lack intrinsic catalytic activity and participate in diverse cellular processes, including differentiation, stress responses, and metabolic regulation. Although NDRGs have been studied primarily in the context of development and cancer, emerging evidence indicates that they both influence components of the canonical insulin signaling pathway and are regulated by insulin. NDRGs are highly expressed in nervous tissue, where insulin signaling is essential for neuronal function and brain metabolism. This mini-review summarizes current knowledge on NDRG function in the nervous system, with emphasis on their links to insulin signaling and insulin-resistance.
Circular RNAs in animals: Biogenesis, function and cell fate control.
Mohammad R, Parfyonova Y, Stafeev I
Biochim Biophys Acta Gene Regul Mech · 2026 Jun · PMID 42105806 · Publisher ↗
In recent years, circular RNAs (circRNAs), a class of RNA molecules characterized by a covalently closed circular structure, have emerged as a complex family of eukaryotic transcripts with distinctive biological features...
In recent years, circular RNAs (circRNAs), a class of RNA molecules characterized by a covalently closed circular structure, have emerged as a complex family of eukaryotic transcripts with distinctive biological features. Beyond their unusual structure, which generally enhances stability by eliminating free ends, circRNAs have attracted attention because their expression is often cell- and tissue-specific and many are conserved across species. These characteristics support diverse molecular functions, including regulation through interactions with microRNAs and RNA-binding proteins (RBP), and in selected contexts, protein translation. The recognition of circRNAs has therefore added an additional layer of post-transcriptional regulation and expanded our understanding of how gene expression programs are organized across cellular states. Notably, an increasing number of studies links circRNA dynamics to differentiation and development, implicating circRNAs in the regulatory logic that governs stemness maintenance and lineage commitment. In this Review, we summarize current knowledge of circRNA biogenesis and function, highlight emerging connections between circRNAs and cell fate decisions, and discuss how these insights can inform the rational development of bioengineered circRNAs as stable yet programmable platforms to steer differentiation toward targeted cell types and support future RNA-based therapeutic strategies.
Structural insights into the interaction between the BH3-like domain of hepatitis B virus X protein and LC3B.
Kusunoki H, Tanaka T, Mizukami T … +2 more , Wakamatsu K, Nagata T
Biochim Biophys Acta Proteins Proteom · 2026 Jul · PMID 42103248 · Publisher ↗
Chronic infection with hepatitis B virus (HBV) remains a global health issue, leading to liver diseases such as chronic hepatitis B, cirrhosis, and hepatocellular carcinoma. The HBV X protein (HBx) promotes viral replica...
Chronic infection with hepatitis B virus (HBV) remains a global health issue, leading to liver diseases such as chronic hepatitis B, cirrhosis, and hepatocellular carcinoma. The HBV X protein (HBx) promotes viral replication and disease progression by interacting with various host proteins. One of its functions involves binding to microtubule-associated protein 1 light chain 3B (LC3B), which mediates selective autophagy and facilitates the removal of the immune-related protein TNFRSF10B (tumor necrosis factor receptor superfamily 10B). However, even the mechanism by which HBx interacts with LC3B remained unclear. In this study, we focused on the HBx-LC3B interaction as a first step and identified a conserved LC3-interacting region motif (Trp120-X-X-Leu123) within the Bcl-2 homology 3 (BH3)-like domain of HBx that directly binds to LC3B. This interaction was characterized using isothermal titration calorimetry and nuclear magnetic resonance (NMR) spectroscopy. We present the first NMR structure of LC3B in complex with the HBx BH3-like peptide, revealing that it adopts an extended conformation upon binding and that Trp120 and Leu123 are essential for LC3B recognition. Notably, the same portion forms an α-helix when binding to B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma extra-large (Bcl-x), suggesting that HBx uses different conformations to interact with distinct targets. This structural plasticity may underlie the multifunctional roles of HBx.
Proteomic profiling of valproic acid-treated zebrafish embryos highlights dysregulation in energy and purine metabolism, and microtubule dynamics: Implications for autism spectrum disorder.
Sürmen S, Sürmen MG, Beler M … +3 more , Ünal İ, Cansız D, Emekli-Alturfan E
Biochim Biophys Acta Proteins Proteom · 2026 Jul · PMID 42103247 · Publisher ↗
Valproate (VPA), a widely used anticonvulsant, is also employed to establish experimental autism spectrum disorder (ASD) models. This study aims to elucidate mechanisms underlying VPA's effects in ASD by analyzing proteo...
Valproate (VPA), a widely used anticonvulsant, is also employed to establish experimental autism spectrum disorder (ASD) models. This study aims to elucidate mechanisms underlying VPA's effects in ASD by analyzing proteomic profiles and oxidant-antioxidant dynamics in zebrafish embryos, uncovering the cellular pathways driving these changes. Zebrafish embryos were exposed to two concentrations of VPA (10 μM and 25 μM) for 72 h post-fertilization (hpf), and LC-MS/MS analyses were performed. Differentially expressed proteins (DEPs) were subjected to bioinformatic analysis to identify associated cellular pathways, and their biological significance was evaluated. Oxidant-antioxidant parameters and locomotor activities were determined. High-dose induced more pronounced proteomic changes, while most of the identified proteins in both groups, including key metabolic enzymes such as adenylate kinase 1 (Ak1), adenosine monophosphate deaminase 1 (Ampd1), pyruvate kinase (Pkmb) and creatine kinase (Ck), exhibited a dose-dependent decrease. Functional enrichment analyses revealed that these alterations were primarily associated with purine metabolism, energy metabolism, and microtubule dynamics. In addition, malondialdehyde, nitric oxide, and glutathione S-transferase, increased in a dose-dependent manner, whereas superoxide dismutase decreased. Decreased average speed, distance swam, and explored areas were found in both VPA treated groups, reflecting early sensorimotor dysfunction. Our findings demonstrate that VPA induces dose-dependent proteomic alterations in zebrafish embryos, with metabolic pathways and cytoskeletal dynamics being particularly affected. Extent of molecular disruptions appears to correlate with VPA concentration, suggesting potential implications for energy homeostasis and cellular structure. Understanding these effects could provide valuable insights into the developmental toxicity mechanisms of VPA and its broader biological significance.
Dysregulated selective translation in cancer: The pivotal functions of RNA-binding proteins and emerging therapeutic avenues.
Hu X, Xie J, Li Y … +2 more , Li K, Wang B
Biochim Biophys Acta Rev Cancer · 2026 May · PMID 42097372 · Publisher ↗
mRNA translation represents an essential layer of gene expression regulation, enabling rapid adaptation to external stimuli and maintenance of cellular homeostasis. Dysregulation of this process is a hallmark of cancer,...
mRNA translation represents an essential layer of gene expression regulation, enabling rapid adaptation to external stimuli and maintenance of cellular homeostasis. Dysregulation of this process is a hallmark of cancer, exploited by malignant cells through alterations in trans-acting factors and cis-regulatory elements to rewire mRNA translation. This reprogramming preferentially translates oncoproteins over tumor-suppressors, ultimately driving tumorigenesis. Although RNA-binding proteins (RBPs) are key trans-regulators involved in almost all steps of mRNA translation, their specific roles in dictating dysregulated translation selectivity in cancer remain to be fully elucidated. Herein, we describe the multi-layered regulation of selective translation by RBPs, which are hijacked by malignant cells to decode the molecular grammars embedded in transcripts, including specific RNA structures, cis-regulatory sequence elements, and epitranscriptomic modifications. Moreover, we comprehensively summarize the pivotal role of RBP-mediated selective translation in shaping multiple malignant behaviors of cancer cells, thereby broadening our understanding of translational control during cancer progression. Therapeutically, we highlight emerging strategies to intervene in these RBP-driven reprogramming of translational circuits, providing an innovative direction for future anti-cancer therapeutics.
Temporal gene expression profiling reveals the protective mechanism of APIP in atrial fibrillation following myocardial infarction.
Zhang YL, Chen TN, He JK … +3 more , Zhu Y, Wang XH, Han X
Biochim Biophys Acta Mol Basis Dis · 2026 Aug · PMID 42097242 · Publisher ↗
BACKGROUND: Atrial fibrillation (AF), the most prevalent form of cardiac arrhythmia, frequently develops as a complication of acute myocardial infarction (MI). Nonetheless, the temporal dynamics of gene expression and ke...
BACKGROUND: Atrial fibrillation (AF), the most prevalent form of cardiac arrhythmia, frequently develops as a complication of acute myocardial infarction (MI). Nonetheless, the temporal dynamics of gene expression and key signaling pathways implicated in the development of AF following MI remain elusive. METHODS: Male wild-type C57BL/6 mice were subjected to coronary artery ligation to induce MI for 1, 3, or 7 days. AF inducibility, atrial diameter, and pathological alterations were examined using programmed intracardiac stimulation, echocardiography, and histological staining. Temporal gene expression profiles were analyzed via microarray analysis. RESULTS: A total of 3364 differentially expressed genes (DEGs) were identified in atrial tissues at 1, 3, and 7 days post-MI compared to sham controls. These DEGs were primarily associated with mitochondrial function and the citrate cycle (TCA cycle) in atrial tissues following MI. Furthermore, co-expression network analysis revealed that APAF1-interacting protein (APIP) was centrally positioned in the gene co-expression network. Moreover, its expression was significantly downregulated in atrial tissues across various time points following MI. Cardiomyocyte-specific overexpression of APIP significantly attenuated atrial remodeling and fibrillation following MI. These beneficial effects were accompanied by elevated Mfn1/Mfn2 and p-Drp1(S637) levels, reduced Drp1 expression levels, and enhanced mitochondrial function. Finally, APIP upregulated citrate synthase (CS), enhanced respiratory complexes I-V, and significantly increased ATP synthesis. CONCLUSIONS: This study systematically characterized temporal changes in differentially expressed genes (DEGs) associated with AF following MI and highlights the protective role of APIP in mitigating AF development post-MI, positioning it as a therapeutic target for AF management.
Mechanism of Helicobacter pylori-induced FOXO3a ubiquitination and degradation in gastric epithelial cells by modifying YWHAZ through B4GALT5-mediated glycosylation during gastric carcinogenesis.
Tuo W, Qu Z, Xiang T … +5 more , Yuan C, Cai Q, Liu G, Wang J, Xiang Y
Biochim Biophys Acta Mol Basis Dis · 2026 May · PMID 42097241 · Publisher ↗
BACKGROUND: Abnormal glycosylation modifications are pivotal in tumorigenesis. However, the mechanism by which Helicobacter pylori (H. pylori) infection affects glycosylation during gastric cancer (GC) progression is not...
BACKGROUND: Abnormal glycosylation modifications are pivotal in tumorigenesis. However, the mechanism by which Helicobacter pylori (H. pylori) infection affects glycosylation during gastric cancer (GC) progression is not well understood. This study investigated how H. pylori infection-related glycosylation contributes to GC, aiming to uncover new therapeutic targets. METHODS: Differentially expressed glycosyltransferases were identified using lectin microarray analysis following H. pylori infection. Beta-1,4-galactosyltransferase 5 (B4GALT5) was specifically identified in both non- and H. pylori infected AGS cells, and GC tissues. The biological functions of B4GALT5 and its regulatory mechanisms in H. pylori infection-mediated GC progression were investigated in vitro and vivo. RESULTS: B4GALT5 expression remarkedly increased in GC cells after H. pylori infection and was linked to poor clinical outcomes in patients with GC. Its overexpression promoted cellular apoptosis, migration, and invasion, while reducing the effectiveness of chemotherapeutic drugs such as cisplatin and paclitaxel. Mechanistic investigations demonstrated that B4GALT5 directly interacts with YWHAZ, enhancing its glycosylation at the N95 site and thus strengthening its binding to FOXO3a. This subsequently led to FOXO3a degradation, preventing its nuclear translocation. In an in-situ tumor-bearing mouse model, B4GALT5 overexpression accelerated tumor growth, whereas mutating the N95 site of YWHAZ reduced this effect. CONCLUSIONS: Our study reveals that H. pylori contribute to gastric carcinogenesis by activating the B4GALT5/YWHAZ/FOXO3a axis via specific glycosylation, suggesting YWHAZ N95 glycosylation as a potential therapeutic target for GC.
Molecular dynamics study of SP-B fragment interactions with model lung surfactant bilayers.
Sheigani V, Jyothini A, Zhao Y … +2 more , Morrow MR, Saika-Voivod I
Biochim Biophys Acta Biomembr · 2026 Jul · PMID 42097192 · Publisher ↗
Respiration depends on a lung surfactant layer to facilitate changes in surface area at the air-water interface. The 79-amino acid lung surfactant protein SP-B, normally present in dimer form, is essential to the functio...
Respiration depends on a lung surfactant layer to facilitate changes in surface area at the air-water interface. The 79-amino acid lung surfactant protein SP-B, normally present in dimer form, is essential to the functioning of lung surfactant. One important aspect of lung surfactant function is the recruitment and cycling of surfactant material to and from bilayer reservoirs. Full utilization of surfactant material available in multilamellar reservoirs presumably requires the formation of contacts between adjacent bilayer surfaces and the formation of connections between leaflets of a given surfactant bilayer. Some fragments of SP-B, including the N-terminal segment SP-B, mimic the effects of full SP-B on model surfactant monolayers and in preparations applied in surfactant-deficient animal model studies. In this work, all-atom molecular dynamics simulations have been carried out on DPPC/POPG model bilayers containing multiple copies of SP-B initially oriented along the bilayer surface, across the bilayer, or randomly as well as on model bilayers containing SP-B randomly oriented on the bilayer surfaces. These results show that, over the microsecond durations of the simulations, SP-B remains largely helical and can be accommodated along the bilayer surface, where it would be available to interact with adjacent bilayers, or across the bilayer which results in local perturbation of the bilayer surface. These observations provide some insight into the possible capacity of the N-terminal segment of SP-B to mediate both interbilayer and intrabilayer interactions that are presumably involved in the lipid assembly reorganization necessary to facilitate surfactant recruitment and recycling from bilayer reservoirs.
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