Molecular and Cellular Biology最新文献_第3页

Loss of Function Mouse Models Reveal a Novel Regulatory Function for ULK1 in Myeloproliferative Neoplasms. 功能缺失小鼠模型揭示了ULK1在骨髓增殖性肿瘤中的一种新的调节功能。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-07-23 DOI: 10.1080/10985549.2025.2529837

Diana Saleiro, Jeremy Q Wen, Markella Zannikou, Brian Lee, Ewa M Kosciuczuk, Sarah D Nehlsen, Adam Munshi, Xintong Chen, Chidera V Oku, Briana Hryhorysak, Jamie N Guillen Magaña, Jorge Heneche, Mariafausta Fischietti, Liliana Ilut, Sara H Small, Anitria Cotton, Trent Hall, Monique A Payton, Elspeth M Beauchamp, Feng Yue, Masha Kocherginsky, Elizabeth T Bartom, Ronald Hoffman, John D Crispino, Leonidas C Platanias

{"title":"Loss of Function Mouse Models Reveal a Novel Regulatory Function for ULK1 in Myeloproliferative Neoplasms.","authors":"Diana Saleiro, Jeremy Q Wen, Markella Zannikou, Brian Lee, Ewa M Kosciuczuk, Sarah D Nehlsen, Adam Munshi, Xintong Chen, Chidera V Oku, Briana Hryhorysak, Jamie N Guillen Magaña, Jorge Heneche, Mariafausta Fischietti, Liliana Ilut, Sara H Small, Anitria Cotton, Trent Hall, Monique A Payton, Elspeth M Beauchamp, Feng Yue, Masha Kocherginsky, Elizabeth T Bartom, Ronald Hoffman, John D Crispino, Leonidas C Platanias","doi":"10.1080/10985549.2025.2529837","DOIUrl":"10.1080/10985549.2025.2529837","url":null,"abstract":"Defining the mechanisms that promote development and progression of myeloproliferative neoplasms (MPNs) is important for understanding the mechanisms of malignant hematopoiesis and critical development of new treatment approaches. We provide evidence for a key and essential role of the kinase ULK1 in MPN pathophysiology. Our studies demonstrate that genetic or pharmacological targeting of ULK1 delays substantially disease development in Jak2V617F-mutant MPN models in vivo and establish that ULK1 activity is required for transcription of genes that control hematopoietic stem cell differentiation. Pharmacological targeting of ULK1 exhibits potent therapeutic effects, resulting in reduction of early stage erythroid progenitors in spleen and bone marrow, decreased levels of hemoglobin, and reduced spleen size in MPN mouse models in vivo. Taken together, these findings provide the first evidence for a novel protumorigenic role for ULK1 downstream of the hyperactive JAK2 signaling in MPNs and raise the potential of ULK1 as a new therapeutic target for the treatment of MPNs.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"395-418"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690901","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

Nuclear Roles for Canonically Lysosomal Proteases. 典型溶酶体蛋白酶的核作用。

IF 2.7 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-06-22 DOI: 10.1080/10985549.2025.2519158

Anna E Enneking, Marc M Khorey, Laura E Edgington-Mitchell

{"title":"Nuclear Roles for Canonically Lysosomal Proteases.","authors":"Anna E Enneking, Marc M Khorey, Laura E Edgington-Mitchell","doi":"10.1080/10985549.2025.2519158","DOIUrl":"10.1080/10985549.2025.2519158","url":null,"abstract":"While the cysteine proteases legumain and cathepsins have traditionally been known as \"lysosomal\" proteases, there is increasing evidence to suggest that they also contribute to a wide range of extralysosomal processes, including in the nucleus. This review aims to provide a comprehensive overview of the current knowledge regarding the translocation of these proteases to the nucleus and their functions on arrival. We discuss possible mechanisms for transporting these proteases to the nucleus, including the presence of a nuclear localization signal sequence or hitchhiking on other proteins that possess this sequence. This transport requires the proteases to first reach the cytosol, which may occur via direct cytosolic translation of truncated proteases or downstream of lysosomal membrane permeabilization. We also discuss the evidence for functions of these proteases upon arrival to the nucleus, including cell cycle progression, cell differentiation, cell death, immune regulation, and epigenetic regulation. As protease substrate profiling methods continue to improve, it is anticipated that many new nuclear substrates and interacting partners will be identified to reveal additional functions for nuclear proteases.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"343-352"},"PeriodicalIF":2.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369067","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

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

IF 3.2 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":3.2,"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 3.2 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":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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 3.2 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":3.2,"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 2.7 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":2.7,"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 3.2 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":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitogen-Activated Protein Kinase Phosphatase-5 is Required for TGF-β Signaling Through a JNK-Dependent Pathway. 丝裂原活化蛋白激酶磷酸酶-5 是通过 JNK 依赖性途径传递 TGF-β 信号的必要条件

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2024-11-28 DOI: 10.1080/10985549.2024.2426665

Sam Dorry, Sravan Perla, Anton M Bennett

{"title":"Mitogen-Activated Protein Kinase Phosphatase-5 is Required for TGF-β Signaling Through a JNK-Dependent Pathway.","authors":"Sam Dorry, Sravan Perla, Anton M Bennett","doi":"10.1080/10985549.2024.2426665","DOIUrl":"10.1080/10985549.2024.2426665","url":null,"abstract":"Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) constitute members of the dual-specificity family of protein phosphatases that dephosphorylate the MAPKs. MKP-5 dephosphorylates the stress-responsive MAPKs, p38 MAPK and JNK, and has been shown to promote tissue fibrosis. Here, we provide insight into how MKP-5 regulates the transforming growth factor-β (TGF-β) pathway, a well-established driver of fibrosis. We show that MKP-5-deficient fibroblasts in response to TGF-β are impaired in SMAD2 phosphorylation at canonical and non-canonical sites, nuclear translocation, and transcriptional activation of fibrogenic genes. Consistent with this, pharmacological inhibition of MKP-5 is sufficient to block TGF-β signaling, and that this regulation occurs through a JNK-dependent pathway. By utilizing RNA sequencing and transcriptomic analysis, we identify TGF-β signaling activators regulated by MKP-5 in a JNK-dependent manner, providing mechanistic insight into how MKP-5 promotes TGF-β signaling. This study elucidates a novel mechanism whereby MKP-5-mediated JNK inactivation is required for TGF-β signaling and provides insight into the role of MKP-5 in tissue fibrosis.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"17-31"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739859","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

Loss of HNRNPK During Cell Senescence Linked to Reduced Production of CDC20. 细胞衰老过程中HNRNPK的丢失与CDC20的产生减少有关。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-01-13 DOI: 10.1080/10985549.2024.2443590

Chang Hoon Shin, Martina Rossi, Krystyna Mazan-Mamczarz, Jennifer L Martindale, Rachel Munk, Apala Pal, Yulan Piao, Jinshui Fan, Supriyo De, Kotb Abdelmohsen, Myriam Gorospe

{"title":"Loss of HNRNPK During Cell Senescence Linked to Reduced Production of CDC20.","authors":"Chang Hoon Shin, Martina Rossi, Krystyna Mazan-Mamczarz, Jennifer L Martindale, Rachel Munk, Apala Pal, Yulan Piao, Jinshui Fan, Supriyo De, Kotb Abdelmohsen, Myriam Gorospe","doi":"10.1080/10985549.2024.2443590","DOIUrl":"10.1080/10985549.2024.2443590","url":null,"abstract":"Cellular senescence is a complex biological response to sublethal damage. The RNA-binding protein HNRNPK was previously found to decrease prominently during senescence in human diploid fibroblasts. Here, analysis of the mechanisms leading to reduced HNRNPK abundance revealed that in cells undergoing senescence, HNRNPK mRNA levels declined transcriptionally and full-length HNRNPK protein was progressively lost, while the abundance of a truncated HNRNPK increased. The ensuing loss of full-length HNRNPK enhanced cell cycle arrest along with increased DNA damage. Analysis of the RNAs enriched after HNRNPK ribonucleoprotein immunoprecipitation (RIP) revealed a prominent target of HNRNPK, CDC20 mRNA, encoding a protein critical for progression through the G2/M phase of the cell division cycle. Silencing HNRNPK markedly decreased the levels of CDC20 mRNA via reduced transcription and stability of CDC20 mRNA, leading to lower CDC20 protein levels; conversely, overexpressing HNRNPK increased CDC20 production. Depletion of either HNRNPK or CDC20 impaired cell proliferation, with a concomitant reduction in the levels of CDK1, a key kinase for progression through G2/M. Given that overexpressing CDC20 in HNRNPK-silenced cells partly alleviated growth arrest, we propose that the reduction in HNRNPK levels in senescent cells contributed to inhibiting proliferation at least in part by suppressing CDC20 production.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"129-141"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971510","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

Noncoding RNA, ncRNA-a3, Epigenetically Regulates TAL1 Transcriptional Program During Erythropoiesis. 非编码RNA， ncRNA-a3，在红细胞生成过程中表观遗传调控TAL1转录程序。

IF 3.2 2区生物学

Molecular and Cellular Biology Pub Date : 2025-01-01 Epub Date: 2025-04-10 DOI: 10.1080/10985549.2025.2482079

Meghana Matur, Yasin Uzun, Xiangguo Shi, Karina Hamamoto, Yi Qiu, Suming Huang

{"title":"Noncoding RNA, ncRNA-a3, Epigenetically Regulates TAL1 Transcriptional Program During Erythropoiesis.","authors":"Meghana Matur, Yasin Uzun, Xiangguo Shi, Karina Hamamoto, Yi Qiu, Suming Huang","doi":"10.1080/10985549.2025.2482079","DOIUrl":"https://doi.org/10.1080/10985549.2025.2482079","url":null,"abstract":"Hematopoietic transcription is a combinatorial control of transcription factors, chromatin modifiers, and non-coding RNAs. TAL1 is a critical regulator of normal and malignant hematopoiesis. However, mechanism underlying regulation of TAL1 activity during erythropoiesis versus leukemogenesis remains elusive. Here, we showed that an enhancer RNA, ncRNA-a3 transcribed from TAL1 + 51Kb-enhancer, is positively correlated with TAL1 locus chromatin accessibility and transcription, and required for TAL1 activation during EPO-induced erythropoiesis. Loss of ncRNA-a3 in CD34+ hematopoietic stem and progenitor cells leads to reduction of TAL1 transcription, followed by impaired terminal erythroid differentiation. The effect of ncRNA-a3 loss on erythroid differentiation is partially rescued by overexpression of Tal1 cDNA, suggesting an important role of ncRNA-a3/TAL1 regulatory axis in erythropoiesis. Mechanistically, ncRNA-a3 regulates long-range chromatin interactions between +51Kb erythroid-specific enhancer, promoter and other regulatory elements in the TAL1 locus to maintain the erythroid interaction hub. By facilitating the binding and recruitment of p300/BRG1 to the TAL1 locus, ncRNA-a3 promotes chromatin accessibility in the TAL1 locus and activates TAL1 transcription program, including subsequent epigenetic and transcriptional activation of erythroid-specific TAL1 target genes. Our study reveals a novel role for ncRNA-a3 in TAL1 dependent erythropoiesis and establishes a new mode of ncRNA-a3 action in TAL1 transcriptional activation.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":"45 4","pages":"169-184"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003898","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