Molecular and Cellular Biology最新文献_第3页

The Copper Chaperone ATOX1 Exhibits Differential Protein-Protein Interactions and Contributes to Skeletal Myoblast Differentiation. 铜伴侣ATOX1表现出差异蛋白-蛋白相互作用，并有助于骨骼肌细胞分化。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-02-04 DOI: 10.1080/10985549.2026.2621941

Nathan Ferguson, Yu Zhang, Alexandra M Perez, Allison T Mezzell, Jason D Fivush, Vinit C Shanbhag, Michael J Petris, Katherine E Vest

{"title":"The Copper Chaperone ATOX1 Exhibits Differential Protein-Protein Interactions and Contributes to Skeletal Myoblast Differentiation.","authors":"Nathan Ferguson, Yu Zhang, Alexandra M Perez, Allison T Mezzell, Jason D Fivush, Vinit C Shanbhag, Michael J Petris, Katherine E Vest","doi":"10.1080/10985549.2026.2621941","DOIUrl":"10.1080/10985549.2026.2621941","url":null,"abstract":"Copper is an essential but potentially toxic nutrient required for a variety of biological functions. Mammalian cells use a complex network of copper transporters and metallochaperones to maintain copper homeostasis. Previous work investigating the role of copper in various disease states has highlighted the importance of copper transporters and metallochaperones. However, questions remain about how copper distribution changes under dynamic conditions like tissue differentiation. We previously reported that the copper exporter ATP7A is required for skeletal myoblast differentiation and that its expression changes in a differentiation dependent manner. Here, we sought to further understand the ATP7A-mediated copper export pathway by examining ATOX1, the copper chaperone that delivers copper to ATP7A. To investigate the role of ATOX1 in a dynamic cellular context, we characterized its protein-protein interactions during myoblast differentiation using the proximity labeling protein APEX2 to biotinylate proteins near ATOX1. We discovered that the ATOX1 interactome undergoes dramatic changes as myoblasts differentiate. These dynamic interactions correlate with distinct phenotypes of ATOX1 deficiency in proliferating and differentiated cells. Together, our results highlight the dynamic interactome of ATOX1 and its contribution to myoblast differentiation.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"391-410"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12983349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119474","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

A Novel Emerin/Nesprin-3 Interaction Mediates Nuclear Size Changes Induced by Oncogenic KRAS in Pancreatic Cancer Cells. 一种新的Emerin/ nesprin3相互作用介导胰腺癌细胞中致癌KRAS诱导的核大小变化。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-05-23 DOI: 10.1080/10985549.2026.2670710

Kayla C LaRue-Nolan, Luis F Flores, Renzo E Vera, Ashley N Sigafoos, Laura Hilario Garcia, Luciana L Almada, Brooke R Tader, Maria F Rodriguez-Quevedo, Danielle G May, David L Marks, Kyle J Roux, Martin E Fernandez-Zapico

{"title":"A Novel Emerin/Nesprin-3 Interaction Mediates Nuclear Size Changes Induced by Oncogenic KRAS in Pancreatic Cancer Cells.","authors":"Kayla C LaRue-Nolan, Luis F Flores, Renzo E Vera, Ashley N Sigafoos, Laura Hilario Garcia, Luciana L Almada, Brooke R Tader, Maria F Rodriguez-Quevedo, Danielle G May, David L Marks, Kyle J Roux, Martin E Fernandez-Zapico","doi":"10.1080/10985549.2026.2670710","DOIUrl":"10.1080/10985549.2026.2670710","url":null,"abstract":"Nuclear envelope (NE) proteins are essential for maintaining nuclear morphology, a central process controlling cellular phenotypes. While these proteins and structures are largely characterized in developmental biology, their function and associated abnormal nuclear morphology in disease, in particular cancer, remain elusive. We reported that throughout pancreatic transformation, oncogenic mutant KRAS (mKRAS) alters cancer cells nuclear size. Furthermore, we identified the NE protein Emerin as a mediator of these nuclear changes. Emerin's function is versatile and dynamic depending on its protein interactions. Here, using a BioID approach we identified the NE protein, Nesprin-3, as a novel Emerin interactor in mKRAS pancreatic cancer cells. Transcriptomic and epigenomic analyses revealed that mKRAS increases Nesprin-3 expression using the transcription factor KLF5 as an effector. Functional studies demonstrated that Nesprin-3 phenocopies Emerin, where knockdown of Nesprin-3 impaired nuclear morphology, proliferation, and gene expression changes induced by mKRAS. Notably, Nesprin-3 overexpression can rescue the nuclear morphology and proliferative phenotype in pancreatic cancer cells with mKRAS knockdown. Finally, utilizing an Emerin mutant that cannot interact with Nesprin-3 we failed to rescue these nuclear size changes. Our data demonstrate a novel mechanism underlying the oncogenic function of KRAS, a major driver of this dismal condition.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"746-765"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13243730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148006076","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

The Yeast AP-1 Factor Yap8 Recruits SAGA and SWI/SNF to Regulate ACR3 Expression and Arsenic Tolerance. 酵母AP-1因子Yap8招募SAGA和SWI/SNF调控ACR3表达和砷耐受性。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-05-23 DOI: 10.1080/10985549.2026.2671974

Ewa Maciaszczyk-Dziubinska, Antonia M Romero, Nallani Vijay Kumar, Jacek Staszewski, Robert Wysocki, Markus J Tamás

{"title":"The Yeast AP-1 Factor Yap8 Recruits SAGA and SWI/SNF to Regulate ACR3 Expression and Arsenic Tolerance.","authors":"Ewa Maciaszczyk-Dziubinska, Antonia M Romero, Nallani Vijay Kumar, Jacek Staszewski, Robert Wysocki, Markus J Tamás","doi":"10.1080/10985549.2026.2671974","DOIUrl":"10.1080/10985549.2026.2671974","url":null,"abstract":"The AP-1-like protein Yap8 is required for arsenic tolerance in the yeast Saccharomyces cerevisiae. Previous work has shown that Yap8 binds to arsenic via critical cysteine residues, which converts Yap8 into an active transcriptional regulator of the arsenic detoxification genes ACR2 and ACR3. However, how Yap8 couples arsenic sensing to gene activation is not fully understood. Here, we provide mechanistic insights into Yap8-dependent gene regulation by identifying cis-regulatory elements and regulatory factors involved. We show that full activation of ACR3 expression requires two Yap8 binding elements in the ACR3 promoter, one accessible and one occluded by a nucleosome. Arsenic stress leads to Yap8-dependent chromatin remodeling which enables Yap8 to bind also to the occluded site. We also demonstrate that Yap8 directly interacts with components of the SWI/SNF chromatin remodeling and SAGA histone acetyl transferase complexes and recruits them to the ACR3 promoter. Accordingly, the cis-regulatory elements and the SAGA and SWI/SNF complexes are all required for arsenic tolerance. Our data is consistent with a model in which arsenic binding to Yap8 results in gene activation and arsenic tolerance via Yap8-dependent recruitment of coactivators and chromatin remodeling factors to the ACR3 promoter.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"837-854"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148006088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Low-Dose Caffeine Exposure Protects the Human Genome from Ionizing Radiation-Induced Damage and Prolongs Mouse Longevity. 低剂量咖啡因暴露可保护人类基因组免受电离辐射引起的损伤并延长小鼠寿命。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2025-11-13 DOI: 10.1080/10985549.2025.2579050

Susmita Kumari, Supriya V Vartak, Sabita Tamang, Sagar S Desai, Stuti Mukerjee, Bibha Choudary, Sathees C Raghavan

{"title":"Low-Dose Caffeine Exposure Protects the Human Genome from Ionizing Radiation-Induced Damage and Prolongs Mouse Longevity.","authors":"Susmita Kumari, Supriya V Vartak, Sabita Tamang, Sagar S Desai, Stuti Mukerjee, Bibha Choudary, Sathees C Raghavan","doi":"10.1080/10985549.2025.2579050","DOIUrl":"10.1080/10985549.2025.2579050","url":null,"abstract":"Coffee is one of the most widely consumed beverages in the world and is a rich source of caffeine, a methylxanthine. Here we show that exposure to caffeine significantly reduces ionizing radiation (IR) induced DNA breaks and resulted in no or minimal G2/M arrest within the human cell, in contrast to IR alone. At the molecular level, we demonstrate that when naked plasmid DNA or oligomeric DNA was irradiated, the number of breaks was significantly less in the presence of caffeine. The observed radioprotection was irrespective of its sequence and was due to quenching of ROS by caffeine. Besides, caffeine treatment in NOS2 knockout (KO) mice exhibited a significantly enhanced survival compared to the corresponding WT mice post-irradiation. The transcriptome analysis revealed the upregulation of the key antioxidant genes (Gpx3, Gpx7, Gpx4, Idh1, etc.) involved in playing a role in ROS homeostasis in caffeine-treated mice following exposure to IR, which was further upregulated in the NOS2 KO mice. The increase in lifespan after whole-body irradiation in mice pretreated with caffeine demonstrates the potential of caffeine-mediated radioprotection and provides compelling evidence that caffeine mitigates the detrimental effects of ionizing radiation by reducing ROS and RNS levels and enhancing the expression of antioxidant genes.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"139-167"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of DNA Methylation Inhibitors on Molecular and Structural Changes in Chromatin Organization in Leukemia Cells. DNA甲基化抑制剂对白血病细胞染色质组织分子和结构变化的影响。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2025-09-29 DOI: 10.1080/10985549.2025.2560965

Przemysław Sareło, Aleksandra Kaczorowska, Marlena Gąsior-Głogowska, Kinga Godkowicz, Weronika Lamperska, Sławomir Drobczyński, Ewa Zioło, Anna Licznerska, Tomasz Wróbel, Halina Podbielska, Wojciech Kałas, Marta Kopaczyńska

{"title":"Effects of DNA Methylation Inhibitors on Molecular and Structural Changes in Chromatin Organization in Leukemia Cells.","authors":"Przemysław Sareło, Aleksandra Kaczorowska, Marlena Gąsior-Głogowska, Kinga Godkowicz, Weronika Lamperska, Sławomir Drobczyński, Ewa Zioło, Anna Licznerska, Tomasz Wróbel, Halina Podbielska, Wojciech Kałas, Marta Kopaczyńska","doi":"10.1080/10985549.2025.2560965","DOIUrl":"10.1080/10985549.2025.2560965","url":null,"abstract":"DNA methylation inhibitors are widely used in treating myeloid malignancies, yet their precise effects on chromatin organization and nuclear architecture remain incompletely understood. Here, the integrated molecular, cellular, and biophysical approaches to investigate the impact of azacitidine (AZA) and decitabine (DEC) on chromatin structure and nuclear mechanics in AML-007 leukemia cells are presented. Confocal microscopy revealed drug-induced alterations in nuclear morphology and actin cytoskeleton organization, with DEC inducing significant nuclear enlargement and disorganization at lower concentrations (1.0 µM) compared to AZA (5.0 µM). Chromatin condensation assays demonstrated that DEC increased chromatin accessibility in a concentration-dependent manner, while AZA produced subtler effects. Optical tweezers measurements showed both agents reduced nuclear stiffness, with DEC exerting a greater impact. Spectroscopic analysis confirmed differential drug incorporation into DNA, with higher methylation loss and structural changes observed following DEC treatment. Refractive index mapping revealed chromatin decompaction, aligning with increased accessibility and nuclear softening. These findings demonstrate that DNA hypomethylating agents exert distinct, concentration-dependent effects on nuclear organization and chromatin structure, which can be quantified through molecular and biophysical readouts. This study underscores the value of integrative methods for revealing epigenetic drug effects on chromatin architecture in leukemia cells.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-20"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacological Inhibition of Valosin-Containing Protein (VCP) Triggers Cardiac Hypertrophy and Heart Failure in Vivo. 体内含缬草苷蛋白（VCP）的药理抑制引发心脏肥厚和心力衰竭。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-05-13 DOI: 10.1080/10985549.2026.2664584

Federica Diofano, Benedict Allhoff, Deung-Dae Park, Larissa Hartmann, Wolfgang Rottbauer, Steffen Just

{"title":"Pharmacological Inhibition of Valosin-Containing Protein (VCP) Triggers Cardiac Hypertrophy and Heart Failure in Vivo.","authors":"Federica Diofano, Benedict Allhoff, Deung-Dae Park, Larissa Hartmann, Wolfgang Rottbauer, Steffen Just","doi":"10.1080/10985549.2026.2664584","DOIUrl":"10.1080/10985549.2026.2664584","url":null,"abstract":"Valosin-containing protein (VCP) is a crucial ATPase involved in maintaining protein homeostasis through the ubiquitin-proteasome system (UPS) and endoplasmic reticulum-associated degradation (ERAD). Dysregulation of VCP has been implicated in neurodegenerative diseases, cancer, and myopathies, and has also been associated with cardiac dysfunction and hypertrophy remodeling. The roles of VCP in the context of cardiomyocyte function and protein homeostasis are still poorly understood. This study examines the effects of pharmacological Vcp inhibition in zebrafish embryos using CB-5083, a selective Vcp ATPase inhibitor. CB-5083-treated embryos exhibited cardiac and skeletal muscle abnormalities, including myofibrillar disorganization, impaired cardiac function, and locomotor defects, closely resembling CRISPR/Cas9-mediated vcp knockout phenotypes. Early developmental inhibition (24-72 hpf) led to severe cardiac impairment and apoptosis, whereas inhibition during late development (72-120 hpf) induced ventricular hypertrophy with preserved contractile function, suggesting a developmental stage-dependent effect. Furthermore, Vcp inhibition was associated with markers of disrupted proteostasis, suggesting UPS dysfunction and ER stress activation. These findings establish a zebrafish model of VCP-related cardiomyopathy, highlight its role in cardiac proteostasis and hypertrophic remodeling, and provide novel insights into disease mechanisms and potential therapeutic targets.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"786-803"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147931385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction. 修正。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-05-21 DOI: 10.1080/10985549.2026.2672906

引用次数: 0

Characterization of the m⁶A Epitranscriptome in Fibroblast Senescence. 成纤维细胞衰老中m6A表转录组的表征。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-06-08 DOI: 10.1080/10985549.2026.2674080

Kotb Abdelmohsen, Nirad Banskota, Martina Rossi, Apala Pal, Mirko Baranzini, Chiara Prampolini, Ethan M Arends, Supriyo De, Myriam Gorospe

{"title":"Characterization of the m6A Epitranscriptome in Fibroblast Senescence.","authors":"Kotb Abdelmohsen, Nirad Banskota, Martina Rossi, Apala Pal, Mirko Baranzini, Chiara Prampolini, Ethan M Arends, Supriyo De, Myriam Gorospe","doi":"10.1080/10985549.2026.2674080","DOIUrl":"10.1080/10985549.2026.2674080","url":null,"abstract":"A critical developmental process affecting aging and age-associated disease, cell senescence is characterized by persistent growth arrest and adaptive gene expression patterns. A common RNA modification, N6-methyladenosine (m6A), regulates gene expression profiles but its impact on senescence has not been studied globally. Here, we elucidated the m6A landscape in proliferating and senescent human fibroblasts using epitranscriptomic microarray and m6A-crosslinking and immunoprecipitation followed by sequencing (CLIP-Seq) analyses. Our findings revealed that while global m6A levels remain stable between proliferating and senescent cells, several transcripts display altered methylation patterns, particularly in senescence-associated pathways like cell cycle, DNA repair, and inflammation. We observed that m6A deposition shifted toward 3'-untranslated regions (UTRs) in senescent cells, although the m6A site modified (the DRACH motif) was unchanged, and we found a positive correlation between m6A levels and transcript abundance. Interestingly, m6A was particularly enriched in mRNAs encoding senescence-associated secretory phenotype (SASP) factors, and silencing METTL3, a major m6A methyltransferase, reduced the stability of certain SASP mRNAs such as IL6 mRNA, suggesting a selective function of m6A in fine-tuning the senescent transcriptome. These findings provide insights into the epitranscriptomic regulation of senescence, and highlight m6A as a potential intervention target in age-related conditions influenced by senescent cells.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"692-710"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TRF-1 Mediates PRC2 Function at Ectopic Telomere Repeats in Neurospora crassa. TRF-1介导粗神经孢子虫异位端粒重复PRC2功能。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-02-17 DOI: 10.1080/10985549.2026.2627225

Colleen C Mumford, Peregrine D Painter, Kevin J McNaught, Hideki Tanizawa, Nolan J Smith, Shinji Honda, Osamu Iwasaki, Sanki Tashiro, Ken-Ichi Noma, Eric U Selker

{"title":"TRF-1 Mediates PRC2 Function at Ectopic Telomere Repeats in Neurospora crassa.","authors":"Colleen C Mumford, Peregrine D Painter, Kevin J McNaught, Hideki Tanizawa, Nolan J Smith, Shinji Honda, Osamu Iwasaki, Sanki Tashiro, Ken-Ichi Noma, Eric U Selker","doi":"10.1080/10985549.2026.2627225","DOIUrl":"10.1080/10985549.2026.2627225","url":null,"abstract":"Telomeres are crucial for maintaining chromosomal integrity and are characterized by repetitive DNA sequences, which may be stabilized by the shelterin protein complex or by formation of secondary structures, such as G-quadruplexes (G4 DNA). Frequently, subtelomeric regions are decorated with di- and tri-methylated lysine 27 on histone H3 (H3K27me), repressive marks catalyzed by Polycomb Repressive Complex 2 that are associated with facultative heterochromatin in many eukaryotes. Our previous work with the filamentous fungus Neurospora crassa demonstrated that native telomere repeats induce H3K27me at ectopic loci. Here we report investigations into the mechanism of this and demonstrate that some non-native telomere repeats can also induce H3K27me. Hi-C analyses demonstrated that ectopic telomeric repeats can interact with native telomeres. Chromatin immunoprecipitation (ChIP) experiments with an anti-G4-DNA antibody showed that establishment of H3K27me was not correlated with the presence of G4 DNA. Other ChIP experiments demonstrated that the telomere repeat-binding protein TRF-1, which has been demonstrated to be a member of the shelterin complex in other systems, binds to interstitial telomere repeats that induce H3K27me. Tethering experiments revealed that TRF-1 binding is sufficient to induce H3K27me. Together these results suggest that TRF-1 plays a crucial role in establishment of H3K27me, and thus repression, at telomere sequences.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"617-631"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146207331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dual Regulatory Roles of USP10 in Tau Pathology and Neuronal Fate During Alzheimer's Disease Progression. USP10在阿尔茨海默病进展中Tau病理和神经元命运中的双重调节作用。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2025-12-08 DOI: 10.1080/10985549.2025.2575950

Masahiko Takahashi, Hiroki Kitaura, Asa Nakahara, Akiyoshi Kakita, Keisuke Watanabe, Taichi Kakihana, Toshifumi Hara, Yoshinori Katsuragi, Manami Yoshita-Takahashi, Sergei Anisimov, Takayuki Abe, Masahiro Fujii

{"title":"Dual Regulatory Roles of USP10 in Tau Pathology and Neuronal Fate During Alzheimer's Disease Progression.","authors":"Masahiko Takahashi, Hiroki Kitaura, Asa Nakahara, Akiyoshi Kakita, Keisuke Watanabe, Taichi Kakihana, Toshifumi Hara, Yoshinori Katsuragi, Manami Yoshita-Takahashi, Sergei Anisimov, Takayuki Abe, Masahiro Fujii","doi":"10.1080/10985549.2025.2575950","DOIUrl":"10.1080/10985549.2025.2575950","url":null,"abstract":"Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by neuronal cell death, brain atrophy, and cognitive decline. Aggregation of Tau protein in neurons is a critical factor in the pathogenesis of AD. Tau aggregates increase as the disease progresses and contribute to neuronal cell death. This study investigated the role of ubiquitin-specific protease 10 (USP10) in Tau pathology and neuronal viability in AD. We found that the expression of USP10 was reduced in the brains of late-stage AD patients with severe Tau aggregate accumulation, which correlated with increased neuronal apoptosis. Mechanistically, our results suggest that USP10 downregulation in late-stage AD may be due to its degradation by the accumulation of p62, an inducer of selective autophagy. Brain-specific Usp10 knockout mice show increased neuronal apoptosis during embryonic development and postnatal brain atrophy. In the P301S-Tau transgenic mice, heterozygous Usp10 knockout lowered Tau levels and slightly improved early survival, suggesting USP10 has stage-dependent effects: its reduction lessens Tau burden early but worsens neuronal loss in late stage. This study identifies USP10 as a key regulator of Tau pathology and neuronal survival in AD.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"114-137"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0