Molecular and Cellular Biology最新文献_第9页

Acyl-CoA Reductase Far1 Deficiency Impairs Ether Lipid Production and Hypomyelination in Mouse Brains. 酰基辅酶a还原酶Far1缺乏损害小鼠脑内乙醚脂质生成和低髓鞘形成。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-09-11 DOI: 10.1080/10985549.2025.2548234

Tenga Takahashi, Kento Otsuka, Takayuki Sassa, Akio Kihara

{"title":"Acyl-CoA Reductase Far1 Deficiency Impairs Ether Lipid Production and Hypomyelination in Mouse Brains.","authors":"Tenga Takahashi, Kento Otsuka, Takayuki Sassa, Akio Kihara","doi":"10.1080/10985549.2025.2548234","DOIUrl":"10.1080/10985549.2025.2548234","url":null,"abstract":"Mammalian cell membranes contain ether lipids, which include an alkyl chain derived from a fatty alcohol that is produced by fatty acyl-CoA reductases (FARs). There are two mammalian FAR genes, FAR1 and FAR2, and mutations in FAR1 cause the peroxisomal fatty acyl-CoA reductase 1 disorder (PFCRD), which is accompanied by various symptoms, including neurological disorders. To date, the contributions of FAR1 and FAR2 to brain ether lipid production and the molecular mechanism of PFCRD have remained unknown. To investigate these, we analyzed knockout (KO) mice of Far1 and Far2. In the brain, the expression levels of Far1 were higher than those of Far2, and Far1 was widely expressed. Lipidomic analyses showed that the quantity of ether lipids ethanolamine-plasmalogens was reduced in Far1 KO mice, with a complementary increase in diacyl-type phosphatidylethanolamines, but not in Far2 KO mice. Electron microscope analysis of the corpus callosum revealed reductions in the percentage of myelinated axons and myelin thickness in Far1 KO mice relative to WT mice. In conclusion, FAR1 is the major FAR isozyme involved in ether lipid synthesis in the brain, and its deficiency causes hypomyelination. We speculate that this hypomyelination is one of the causes of the neurological symptoms of PFCRD.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"495-510"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033738","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

Histone Acetyltransferases Gcn5 and Esa1 Regulate Occupancy of RSC to Maintain Nucleosome-Depleted Regions and Promote RSC Recruitment to Coding Regions Genome-Wide in Saccharomyces cerevisiae. 在酿酒酵母中，组蛋白乙酰转移酶Gcn5和Esa1调节RSC的占用以维持核小体缺失区域，并促进RSC向全基因组编码区域的招募。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-09-17 DOI: 10.1080/10985549.2025.2555901

Emily Biernat, Mansi Verma, Matthew Werick, Uzair Khan, Sama Joseph, Chhabi K Govind

{"title":"Histone Acetyltransferases Gcn5 and Esa1 Regulate Occupancy of RSC to Maintain Nucleosome-Depleted Regions and Promote RSC Recruitment to Coding Regions Genome-Wide in Saccharomyces cerevisiae.","authors":"Emily Biernat, Mansi Verma, Matthew Werick, Uzair Khan, Sama Joseph, Chhabi K Govind","doi":"10.1080/10985549.2025.2555901","DOIUrl":"10.1080/10985549.2025.2555901","url":null,"abstract":"Chromatin remodelers are important for maintaining chromatin structure and regulating gene expression. In this study, we investigated the roles of histone acetyltransferases (HATs) Gcn5 and Esa1 in regulating RSC and histone occupancy on chromatin, as well as their impact on transcription across the genome. Our findings reveal distinct effects of HATs on RSC occupancy in promoters and ORFs. The lack of HATs leads to the accumulation of RSC, and it was greater in nucleosome-depleted regions (NDRs) containing fragile nucleosomes (FNs), relative to other NDRs. The increased RSC NDR-binding was greater in Esa1-deficient cells than in those lacking Gcn5. The increased RSC binding was not seen in cells lacking the H3 or H4 tails. The mutants also led to significant increases in histone occupancies around the NDRs genome-wide. Overall, the data suggest that hypoacetylated tails may recruit RSC to NDRs, especially to FN-containing NDRs, and that subsequent histone acetylation enhances histone eviction. The HAT mutants also exhibited reduced recruitment of TBP and Pol II. In contrast to the promoters, RSC occupancies were significantly reduced in transcribed ORFs in the HAT mutants. Thus, our data implicate HATs and RSC in maintaining NDRs, regulating chromatin structure, and promoting transcription.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"623-645"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12834339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075791","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

Defining and Harnessing the Megakaryocyte/Platelet Checkpoint. 定义和利用巨核细胞/血小板检查点。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-02-24 DOI: 10.1080/10985549.2025.2451279

Alexandra Mazharian, Yotis A Senis

{"title":"Defining and Harnessing the Megakaryocyte/Platelet Checkpoint.","authors":"Alexandra Mazharian, Yotis A Senis","doi":"10.1080/10985549.2025.2451279","DOIUrl":"10.1080/10985549.2025.2451279","url":null,"abstract":"Platelets, or thrombocytes are anucleate cell fragments of megakaryocytes (MKs) that are highly reactive to sites of vascular injury and implicated in many pathologies. However, the molecular mechanisms regulating the number and activity of platelets in the circulation remain undefined. The primary outstanding question remains what is the triggering mechanism of platelet production, or thrombopoiesis? Putative stimulatory factors and mechanical forces are thought to drive this process, but none induce physiological levels of thrombopoiesis. Intrinsic inhibitory mechanisms that maintain MKs in a refractory state in sites of thrombopoiesis are conspicuously overlooked, as well as extrinsic cues that release this brake system, allowing asymmetric platelet production to proceed toward the vascular lumen. Here we introduce the novel concept of a MK/platelet checkpoint, putative components and a working model of how it may be regulated. We postulate that the co-inhibitory receptor G6b-B and the non-transmembrane protein-tyrosine phosphatases (PTPs) Shp1 and Shp2 form an inhibitory complex that is the primary gatekeeper of this checkpoint, which is spatiotemporally regulated by the receptor-type PTP CD148 and vascular heparan sulfate proteoglycans. By advancing this alternative model of thrombopoiesis, we hope to stimulate discourse and a shift in how we conceptualize and address this fundamental question.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"116-128"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483701","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

HEB Restrains Effector Gene Expression during Early CD8⁺ Memory Precursor T Cell Differentiation. HEB在早期CD8+记忆前体T细胞分化过程中抑制效应基因表达

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-05-26 DOI: 10.1080/10985549.2025.2505730

Joanne Pui-Ting Leung, Siamak Haddadi, Michael J Geuenich, Alara Tuncer, Vivien Musiime, Chao Wang, Juan-Carlos Zúñiga-Pflücker, Kieran R Campbell, Michele K Anderson

{"title":"HEB Restrains Effector Gene Expression during Early CD8+ Memory Precursor T Cell Differentiation.","authors":"Joanne Pui-Ting Leung, Siamak Haddadi, Michael J Geuenich, Alara Tuncer, Vivien Musiime, Chao Wang, Juan-Carlos Zúñiga-Pflücker, Kieran R Campbell, Michele K Anderson","doi":"10.1080/10985549.2025.2505730","DOIUrl":"10.1080/10985549.2025.2505730","url":null,"abstract":"Memory T cells are essential for maintaining long-term adaptive immunity. Memory cell precursors and short-lived effector cells emerge from undifferentiated naïve T cells directly downstream of TCR signaling but little is known about how this lineage choice is regulated at the molecular level. The transcription factor HEB is known to be an important regulator of thymic T cell development, but how it functions in peripheral T cell differentiation is poorly understood. We assessed the role of HEB in the differentiation of memory-like T cell precursors by inducing TCR signaling in CD8 T cells in the context of memory-polarizing cytokines or inflammatory conditions and found that CD8 T cells from HEB-deficient mice underwent accelerated differentiation as compared to WT cells. Transcriptomic analysis revealed aberrant upregulation of immune response genes and decreased expression of genes promoting stemness from the earliest stages of post-TCR signal activation and persisting throughout the course of differentiation. In addition, acute viral infection of HEB cKO mice resulted in enhanced memory precursor cell formation and increased effector functionality. Therefore, we have identified HEB as a central participant in the gene regulatory networks that regulate early CD8 memory T cell differentiation and effector gene expression. This study showed that naïve CD8 T cells lacking HEB exhibit increased TCR signal strength and loss of signatures of stem-ness, revealing a role for HEB in promoting immune memory.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"283-300"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12765225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142911","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

Immune Regulation of Itaconate and Its Derivatives in Liver Diseases. 衣康酸及其衍生物在肝脏疾病中的免疫调节作用。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-09-10 DOI: 10.1080/10985549.2025.2553660

Tianning Ge, Yifei Zhang

{"title":"Immune Regulation of Itaconate and Its Derivatives in Liver Diseases.","authors":"Tianning Ge, Yifei Zhang","doi":"10.1080/10985549.2025.2553660","DOIUrl":"10.1080/10985549.2025.2553660","url":null,"abstract":"Over the past few decades, liver disease has emerged as one of the leading causes of death worldwide. Liver injury is frequently associated with infections, alcohol consumption, or obesity, which trigger hepatic inflammation and ultimately lead to progressive fibrosis and carcinoma. Although various cell populations contribute to inflammatory and fibrogenic processes in the liver, macrophages serve as a pivotal mediator. Hepatic macrophages exhibit substantial heterogeneity and perform diverse functions that depend on the pathological microenvironment. The immune response gene 1 (IRG1), a critical metabolic regulatory gene, encodes the mitochondrial enzyme aconitate decarboxylase 1 (ACOD1), which influences macrophage functional polarization by promoting the synthesis of itaconate, a metabolite produced via a side pathway of the tricarboxylic acid (TCA) cycle. Increasing evidence indicates that itaconate and its derivatives exert immunomodulatory effects in processes such as oxidative stress, viral infection, inflammation, tumorigenesis, and wound healing, thereby demonstrating significant potential for treating liver disorders. In this review, we summarize the roles of itaconate and its derivatives in liver diseases and their underlying mechanisms, thereby providing insights into the therapeutic potential of targeting macrophages.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"585-602"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030063","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

Causes, Consequences and Challenges of Intron Retention in lncRNAs. lncrna中内含子保留的原因、后果和挑战。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-08-08 DOI: 10.1080/10985549.2025.2539755

Manish Kumar, Ioannis Grammatikakis

引用次数: 0

Loss of E-Cadherin Alters Cigarette Smoke Extract (CSE)-Induced Damage and Repair Responses in Human Airway Epithelial Cells; Implications for Chronic Obstructive Pulmonary Disease (COPD). e -钙粘蛋白的缺失改变了香烟烟雾提取物（CSE）诱导的人气道上皮细胞损伤和修复反应对慢性阻塞性肺疾病（COPD）的影响。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-09-29 DOI: 10.1080/10985549.2025.2560946

Xinzi Zheng, Kingsley Okechukwu Nwozor, Marnix Jonker, Marissa Wisman, Martijn C Nawijn, Irene H Heijink

{"title":"Loss of E-Cadherin Alters Cigarette Smoke Extract (CSE)-Induced Damage and Repair Responses in Human Airway Epithelial Cells; Implications for Chronic Obstructive Pulmonary Disease (COPD).","authors":"Xinzi Zheng, Kingsley Okechukwu Nwozor, Marnix Jonker, Marissa Wisman, Martijn C Nawijn, Irene H Heijink","doi":"10.1080/10985549.2025.2560946","DOIUrl":"10.1080/10985549.2025.2560946","url":null,"abstract":"COPD is characterized by airway epithelial barrier dysfunction. We hypothesized that downregulation of E-cadherin results in abnormal responses to cigarette smoke extract (CSE) with impaired repair and increased pro-inflammatory activity. We used CRISPR-Cas9-engineered 16HBE cells with 1-2 copies of the CDH1 gene encoding E-cadherin (CDH1+/+ or CDH1+/-) to study effects on tight junctional protein zonula occludens (ZO-1), CSE-induced epithelial barrier dysfunction using electric cell-substrate impedance sensing and pro-inflammatory cytokine production. In airway epithelial cells (AECs) from nine COPD stage IV transplant lungs and tracheobronchial tissue of nine non-COPD donors, we assessed E-cadherin, ZO-1 and pro-inflammatory cytokines. Lower electrical resistance in CDH1+/- 16HBE cells was accompanied by ZO-1 delocalization. CSE exposure induced transient barrier dysfunction, from which CDH1+/- cells recovered more slowly than CDH1+/+ cells. Similarly, CDH1+/- cells showed a delayed repair response upon wounding, while gene expression and secretion of pro-inflammatory cytokines were higher in unexposed cells (CXCL8, IL-1α) and/or showed a stronger CSE-induced increase (IL-1α, GM-CSF). AECs from COPD patients displayed lower E-cadherin and TJP1 levels and higher CSE-induced IL1A expression compared to control. Downregulation of E-cadherin resulted in disrupted ZO-1 expression, aggravated CSE-induced barrier dysfunction, impaired recovery from injury and a more pro-inflammatory epithelial phenotype in 16HBE cells.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"481-494"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186260","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

Impact of Short-Term Lipid Overload on Whole-Body Physiology. 短期脂质超载对全身生理的影响。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2024-12-27 DOI: 10.1080/10985549.2024.2438814

Umur Keles, Nisan Ece Kalem-Yapar, Hanna Hultén, Li Na Zhao, Philipp Kaldis

{"title":"Impact of Short-Term Lipid Overload on Whole-Body Physiology.","authors":"Umur Keles, Nisan Ece Kalem-Yapar, Hanna Hultén, Li Na Zhao, Philipp Kaldis","doi":"10.1080/10985549.2024.2438814","DOIUrl":"10.1080/10985549.2024.2438814","url":null,"abstract":"Complex metabolic diseases due to overnutrition such as obesity, type 2 diabetes, and fatty liver disease are a major burden on the healthcare system worldwide. Current research primarily focuses on disease endpoints and trying to understand underlying mechanisms at relatively late stages of the diseases, when irreversible damage is already done. However, complex interactions between physiological systems during disease development create a problem regarding how to build cause-and-effect relationships. Therefore, it is essential to understand the early pathophysiological effects of overnutrition, which can help us understand the origin of the disease and to design better treatment strategies. Here, we focus on early metabolic events in response to high-fat diets (HFD) in rodents. Interestingly, insulin resistance, fatty liver, and obesity-promoting systemic inflammatory responses are evident within a week when mice are given consecutive HFD meals. However, as shown in human studies, these effects are usually not visible after a single meal. Overall, these results suggest that sustained HFD-intake within days can create a hyperlipidemic environment, globally remodeling metabolism in all affected organs and resembling some of the important disease features.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"47-58"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896060","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

Differential Transcriptional Activity of ΔNp63β Is Encoded by an Isoform-Specific C-Terminus. ΔNp63β的差异转录活性是由一个同工型特异性c端编码的。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-06-23 DOI: 10.1080/10985549.2025.2514529

Abby A McCann, Morgan A Sammons

{"title":"Differential Transcriptional Activity of ΔNp63β Is Encoded by an Isoform-Specific C-Terminus.","authors":"Abby A McCann, Morgan A Sammons","doi":"10.1080/10985549.2025.2514529","DOIUrl":"10.1080/10985549.2025.2514529","url":null,"abstract":"p63 is a clinically relevant transcription factor heavily involved in development and disease. Mutations in the p63 DNA-binding domain cause severe developmental defects and overexpression of p63 plays a role in the progression of epithelial-associated cancers. Unraveling the specific biochemical mechanisms underlying these phenotypes is made challenging by the presence of multiple p63 isoforms and their shared and unique contributions to development and disease. Here, we explore the function of the p63 isoforms ΔNp63ɑ and ΔNp63β to determine the contribution of C-terminal splice variants on known and unique molecular and biochemical activities. Using RNA-seq and ChIP-seq on isoform-specific cell lines, we show that ΔNp63β regulates both canonical ΔNp63ɑ targets and a unique set of genes with varying biological functions. We demonstrate that most genomic binding sites are shared, however the enhancer-associated histone modification H3K27ac is highly enriched at ΔNp63β binding sites relative to ΔNp63ɑ. An array of ΔNp63β C-terminal mutants demonstrates the importance of isoform-specific C-terminal domains in regulating these unique activities. Our results provide novel insight into differential activities of p63 C-terminal isoforms and suggest future directions for dissecting the functional relevance of these and other transcription factor isoforms in development and disease.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"369-385"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369066","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

Investigating the Aggregation and Prionogenic Properties of Human Cancer-Related Proteins. 研究人类癌症相关蛋白的聚集和致朊特性。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-03-31 DOI: 10.1080/10985549.2025.2481054

Dustin Goncharoff, Zhiqiang Du, Shriram Venkatesan, Brandon Cho, Jenny Zhao, Milad J Alasady, Dalton Huey, Hannah Ma, Jake Rosenthal, Alexander Turenitsa, Coral Feldman, Randal Halfmann, Marc L Mendillo, Liming Li

{"title":"Investigating the Aggregation and Prionogenic Properties of Human Cancer-Related Proteins.","authors":"Dustin Goncharoff, Zhiqiang Du, Shriram Venkatesan, Brandon Cho, Jenny Zhao, Milad J Alasady, Dalton Huey, Hannah Ma, Jake Rosenthal, Alexander Turenitsa, Coral Feldman, Randal Halfmann, Marc L Mendillo, Liming Li","doi":"10.1080/10985549.2025.2481054","DOIUrl":"10.1080/10985549.2025.2481054","url":null,"abstract":"Cancer encompasses a range of severe diseases characterized by uncontrolled cell growth and the potential for metastasis. Understanding the mechanism underlying tumorigenesis has been a central focus of cancer research. Self-propagating protein aggregates, known as prions, are linked to various biological functions and diseases, particularly those related to mammalian neurodegeneration. However, it remains unclear whether prion-like mechanisms contribute to tumorigenesis and cancer. Using a combined approach of algorithmic predictions, alongside genetic and biochemical experimentation, we identified numerous cancer-associated proteins prone to aggregation, many of which contain prion-like domains (PrLDs). These predictions were experimentally validated for both aggregation and prion-formation. We demonstrate that several PrLDs undergo nucleation-limited amyloid formation, which can alter protein activity in a mitotically heritable fashion. These include SSXT, a subunit of the chromatin-remodeling BAF (hSWI/SNF) complexes; CLOCK, a core component of the circadian clock; and EPN4, a clathrin-interacting protein involved in protein trafficking between the trans-Golgi network and endosomes. The prions formed by these PrLDs occurred in multiple variants and depended on Hsp104, a molecular chaperone with disaggregase activity. Our results reveal an inherent tendency for prion-like aggregation in human cancer-associated proteins, suggesting a potential role for such aggregation in the epigenetic changes driving tumorigenesis.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"154-168"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12983077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753558","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