Molecular and Cellular Biology最新文献_第5页

The Role of the RhoA Activating Protein Net1 in Cancer Initiation and Progression. RhoA激活蛋白Net1在癌症发生和发展中的作用。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2025-12-25 DOI: 10.1080/10985549.2025.2605086

Yan Zuo, Stephanie A Planque, Jeffrey A Frost

引用次数: 0

Acetylation-Dependent Histone H2AX Exchange Suppresses Pathological Senescence via MDC1 Degradation. 乙酰化依赖性组蛋白H2AX交换通过MDC1降解抑制病理性衰老。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-01-06 DOI: 10.1080/10985549.2025.2596729

Masae Ikura, Kanji Furuya, Yasunori Horikoshi, Satoshi Tashiro, Takuma Shiraki, Tsuyoshi Ikura

{"title":"Acetylation-Dependent Histone H2AX Exchange Suppresses Pathological Senescence via MDC1 Degradation.","authors":"Masae Ikura, Kanji Furuya, Yasunori Horikoshi, Satoshi Tashiro, Takuma Shiraki, Tsuyoshi Ikura","doi":"10.1080/10985549.2025.2596729","DOIUrl":"10.1080/10985549.2025.2596729","url":null,"abstract":"Cellular senescence has a dual role in both tumor suppression and the promotion of age-related diseases. This paradox suggests the existence of functionally distinct \"beneficial\" and \"detrimental\" senescent states, yet the molecular basis that governs their fate has remained elusive. Here, we reveal that the dynamic exchange of histone H2AX on chromatin functions as an essential quality control mechanism that dictates the quality of senescence. We demonstrate that the histone acetyltransferase TIP60, in complex with the chaperone FACT, acetylates H2AX at lysine 5 (K5), which in turn drives its dynamic exchange. This histone exchange is indispensable for promoting the degradation of the DNA damage response mediator MDC1, a process we uncover is mediated by a novel DNA-PKcs-p97 signaling axis. Disruption of this TIP60-FACT-H2AX exchange pathway leads to the hyperaccumulation of MDC1 and a shift toward error-prone nonhomologous end joining (NHEJ), inducing a pathological senescent state with oncogenic potential. Our study redefines histone exchange from a passive chromatin event to an active regulatory hub that determines the fate of aging cells. These findings provide a molecular basis for the heterogeneity of senescence and establish a rationale for developing \"senomorphic\" therapies aimed at improving the quality of aging.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"297-317"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912288","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

Cancer-Associated DAXX Mutations Reveal a Critical Role for ATRX Localization in ALT Suppression. 癌症相关DAXX突变揭示ATRX定位在ALT抑制中的关键作用

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2025-12-21 DOI: 10.1080/10985549.2025.2597468

Sarah F Clatterbuck Soper, Robert L Walker, Marbin A Pineda, Yuelin J Zhu, James L T Dalgleish, Jasmine Wang, Paul S Meltzer

{"title":"Cancer-Associated DAXX Mutations Reveal a Critical Role for ATRX Localization in ALT Suppression.","authors":"Sarah F Clatterbuck Soper, Robert L Walker, Marbin A Pineda, Yuelin J Zhu, James L T Dalgleish, Jasmine Wang, Paul S Meltzer","doi":"10.1080/10985549.2025.2597468","DOIUrl":"10.1080/10985549.2025.2597468","url":null,"abstract":"To maintain genome stability, proliferating cells must enact a program of telomere maintenance. While most tumors maintain telomeres using telomerase, a subset of tumors utilize a DNA-templated process termed alternative lengthening of telomeres or ALT. ALT is associated with mutations in the ATRX/DAXX/H3.3 histone chaperone complex, which is responsible for deposition of histone variant H3.3 at heterochromatic regions of the genome including telomeres. We wished to better understand the role DAXX plays in ALT suppression, and to determine which disease-associated DAXX mutations are unable to suppress ALT. To answer this question, we leveraged the G292 cell line, in which ATRX is wild-type but DAXX has undergone a fusion event. Restoration of wild-type DAXX in G292 localizes ATRX and abrogates ALT. Using this model system, we tested the ability of disease-associated DAXX missense variants to suppress ALT. Missense mutations in the ATRX binding domain, the histone binding domain, and the C-terminal SUMO interaction motif reduce the ability of DAXX to suppress ALT. Unexpectedly, we find that mutations in the DAXX histone binding domain lead to failure of ATRX localization. We conclude that a key function of DAXX in ALT suppression is the localization of ATRX to nuclear foci.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"459-474"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804907","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

PKM2-DNMT3A-SMAD2 Axis Regulates Cell Proliferation via Histone Lactylation in Breast Cancer. PKM2-DNMT3A-SMAD2轴通过组蛋白乳酸化调节乳腺癌细胞增殖。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-02-25 DOI: 10.1080/10985549.2026.2631551

Abin Sabu, Deepak Pant, Srinivas Abhishek Mutnuru, K Varun, Parik Kakani, Sanjeev Shukla

{"title":"PKM2-DNMT3A-SMAD2 Axis Regulates Cell Proliferation via Histone Lactylation in Breast Cancer.","authors":"Abin Sabu, Deepak Pant, Srinivas Abhishek Mutnuru, K Varun, Parik Kakani, Sanjeev Shukla","doi":"10.1080/10985549.2026.2631551","DOIUrl":"10.1080/10985549.2026.2631551","url":null,"abstract":"Cancer develops from the unregulated proliferation of cells, influenced by a confluence of genetic mutations and epigenetic modifications that disrupt normal regulatory networks. In recent years, cellular metabolism has emerged as an important factor in controlling epigenetic states by connecting the availability of intracellular metabolites to changes in chromatin. One such metabolite is lactate, a glycolytic by-product produced in large amounts in tumor cells because of the Warburg effect. Lactate has been found to be a substrate for histone lactylation, a recently discovered epigenetic mark that affects gene expression. Although histone lactylation is gaining importance in cancer biology, its functional role in breast cancer remains inadequately elucidated. In this study, we utilized a lactate-deficient cell line created by the knockout of PKM2 to examine the effects of promoter-level histone H3 lysine 18 lactylation (H3K18la) on the regulation of the DNMT3A gene, which subsequently influences SMAD2 expression and modulates the TGF-β signaling pathway and cellular proliferation in breast cancer. Our findings elucidate a novel metabolic-epigenetic axis that cancer cells utilize to drive tumorigenesis.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"584-595"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284406","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

Gasdermin D Inhibition Attenuates Mitochondrial Damage and Cardiomyocyte Pyroptosis in Heart Failure with Preserved Ejection Fraction. 气皮蛋白D抑制可减轻射血分数保留的心力衰竭患者线粒体损伤和心肌细胞焦亡。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-07-07 DOI: 10.1080/10985549.2026.2693284

Linlin Chen, Zhiming Jiang, Cheng Li, Hao He, Yulian Yin, Dong Li

{"title":"Gasdermin D Inhibition Attenuates Mitochondrial Damage and Cardiomyocyte Pyroptosis in Heart Failure with Preserved Ejection Fraction.","authors":"Linlin Chen, Zhiming Jiang, Cheng Li, Hao He, Yulian Yin, Dong Li","doi":"10.1080/10985549.2026.2693284","DOIUrl":"10.1080/10985549.2026.2693284","url":null,"abstract":"Heart failure with preserved ejection fraction (HFpEF) represents the most prevalent subtype of heart failure globally, with its underlying pathogenesis remaining incompletely elucidated. Pyroptosis and mitochondrial dysfunction have been implicated in HFpEF progression. In addition, gasdermin D (GSDMD) has been shown to mediate both mitochondrial dysfunction and pyroptosis, yet the specific regulatory mechanisms involved in HFpEF remain to be elucidated. In this study, we found that HFpEF mouse models exhibited elevated blood glucose and blood pressure, impaired diastolic cardiac function, upregulated serum NT-proBNP, increased heart weight-to-tibia length (HW/TL) ratio, reduced exercise tolerance, obvious myocardial structural damage, excessive mitochondrial ROS accumulation, increased mitochondrial GSDMD-N expression, mitochondrial morphological abnormalities, and activated myocardial pyroptosis pathway. Treatment with GI-Y2 significantly ameliorated these changes. Collectively, GSDMD contributes to HFpEF progression by promoting mitochondrial damage and cardiomyocyte pyroptosis.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"826-836"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397398","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

Systematic Screening via WGCNA, Machine Learning, and Validation Identifies C3 and CFD as Prognostically Significant Regulators in GIST Progression. 通过WGCNA、机器学习和验证系统筛选确定C3和CFD是GIST进展的预后重要调节因子。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-02-24 DOI: 10.1080/10985549.2026.2631549

Yuxuan Ma, Xin Liu, Yuhao Wang, Shu Wang, Haoyuan Wang, Yan Zhao, Chaosheng Peng, Jianjun Yang

{"title":"Systematic Screening via WGCNA, Machine Learning, and Validation Identifies C3 and CFD as Prognostically Significant Regulators in GIST Progression.","authors":"Yuxuan Ma, Xin Liu, Yuhao Wang, Shu Wang, Haoyuan Wang, Yan Zhao, Chaosheng Peng, Jianjun Yang","doi":"10.1080/10985549.2026.2631549","DOIUrl":"10.1080/10985549.2026.2631549","url":null,"abstract":"Gastrointestinal stromal tumor (GIST), the most common gastrointestinal mesenchymal neoplasm, remains poorly understood at the molecular level, limiting precise diagnosis and targeted therapy. This study aimed to systematically identify key GIST-associated genes through multiomic integration and experimental validation. We analyzed three GIST transcriptomic datasets from GEO, corrected batch effects via surrogate variable analysis (SVA), and identified 61 differentially expressed genes (DEGs) using limma. Weighted gene co-expression network analysis (WGCNA) highlighted progression-related modules, which were refined using random forests and LASSO regression to prioritize C3 and complement factor D (CFD), both of which showed robust diagnostic performance (AUC: 0.928 for C3; 0.955 for CFD). Experimental validation confirmed C3/CFD downregulation in GIST tissues, correlating with advanced stage and poor survival. Functional assays demonstrated their tumor-suppressive roles, inhibiting GIST cell proliferation, colony formation, and migration. CIBERSORT analysis linked C3/CFD to altered immune infiltration, while ssGSEA/GSEA implicated their involvement in lipid metabolism and oxidative phosphorylation. These findings establish C3 and CFD as critical tumor-suppressive biomarkers that modulate the immune response and reprogram metabolism, offering new avenues for GIST diagnosis and therapy.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"411-432"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284393","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

Recent Insights into Mechanisms Regulating the Proteasome: Implications for Human Disease. 调节蛋白酶体机制的最新见解：对人类疾病的影响。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2025-11-20 DOI: 10.1080/10985549.2025.2587085

Rintaro Sumikama, Yuri Shibata, Rihan Wu, Shigeo Murata

{"title":"Recent Insights into Mechanisms Regulating the Proteasome: Implications for Human Disease.","authors":"Rintaro Sumikama, Yuri Shibata, Rihan Wu, Shigeo Murata","doi":"10.1080/10985549.2025.2587085","DOIUrl":"10.1080/10985549.2025.2587085","url":null,"abstract":"Since its discovery several decades ago, the proteasome has been recognized as one of the most complex and highly evolved proteolytic systems. Through the selective and rapid degradation of ubiquitinated proteins, it plays a pivotal role in maintaining cellular proteostasis and governing essential biological processes such as cell cycle regulation and signal transduction. Recent advances in cryo-electron microscopy (cryo-EM), together with developments in mass spectrometry and large-scale genetic screening, have provided unprecedented insights into proteasome biology. These approaches have not only revealed the proteasome as a precisely engineered molecular machine optimized for substrate specificity and efficient degradation, but have also facilitated the identification of previously unrecognized regulatory factors and post-translational modifications that fine-tune its activity. Moreover, accumulating evidence has demonstrated that proteasome capacity is tightly regulated at multiple levels, including transcriptional control, assembly dynamics, and subcellular localization, to meet diverse cellular demands and preserve proteostasis. Importantly, dysregulation of these processes is linked to human diseases, underscoring the proteasome's central role in cellular physiology and its promise as a therapeutic target. Ongoing research is uncovering new regulatory layers and structural complexities, highlighting the proteasome's indispensable and versatile role in health and disease.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"487-504"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145564100","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

Mitochondria and Lipids in Cellular Signaling of the Brain: from Physiology to Neurodegeneration. 脑细胞信号中的线粒体和脂质：从生理学到神经退行性变。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-01-02 DOI: 10.1080/10985549.2025.2607428

Plamena R Angelova, Lauren Millichap, Andrey Y Abramov

引用次数: 0

The Role the Saccharomyces cerevisiae Nonsense-Mediated mRNA Decay Pathway Plays in Metal Toxin Uptake and Detoxification. 酿酒酵母无义介导的mRNA衰变途径在金属毒素摄取和解毒中的作用。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2025-12-29 DOI: 10.1080/10985549.2025.2603952

Sunday Olaniyan, Jacqueline Carroll, Stephnie Nwaiwu, Bessie W Kebaara

引用次数: 0

Molecular Mechanisms of Transcription Factors with Dual Activator and Repressor Functions. 具有双重激活和抑制功能的转录因子的分子机制。