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CDK11, a splicing-associated kinase regulating gene expression. CDK11，一种调节基因表达的剪接相关激酶。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-08-01 Epub Date: 2024-09-07 DOI: 10.1016/j.tcb.2024.08.004
Milan Hluchý, Dalibor Blazek
{"title":"CDK11, a splicing-associated kinase regulating gene expression.","authors":"Milan Hluchý, Dalibor Blazek","doi":"10.1016/j.tcb.2024.08.004","DOIUrl":"10.1016/j.tcb.2024.08.004","url":null,"abstract":"<p><p>The ability of a cell to properly express its genes depends on optimal transcription and splicing. RNA polymerase II (RNAPII) transcribes protein-coding genes and produces pre-mRNAs, which undergo, largely co-transcriptionally, intron excision by the spliceosome complex. Spliceosome activation is a major control step, leading to a catalytically active complex. Recent work has showed that cyclin-dependent kinase (CDK)11 regulates spliceosome activation via the phosphorylation of SF3B1, a core spliceosome component. Thus, CDK11 arises as a major coordinator of gene expression in metazoans due to its role in the rate-limiting step of pre-mRNA splicing. This review outlines the evolution of CDK11 and SF3B1 and their emerging roles in splicing regulation. It also discusses how CDK11 and its inhibition affect transcription and cell cycle progression.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"702-716"},"PeriodicalIF":18.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Targeting SHP1 and SHP2 to suppress tumors and enhance immunosurveillance. 靶向 SHP1 和 SHP2 抑制肿瘤并增强免疫监视。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-08-01 Epub Date: 2024-11-21 DOI: 10.1016/j.tcb.2024.10.008
Yijun Zhao, Linjia Jiang
{"title":"Targeting SHP1 and SHP2 to suppress tumors and enhance immunosurveillance.","authors":"Yijun Zhao, Linjia Jiang","doi":"10.1016/j.tcb.2024.10.008","DOIUrl":"10.1016/j.tcb.2024.10.008","url":null,"abstract":"<p><p>The nonreceptor tyrosine phosphatases (PTPS) SHP1 and SHP2 have crucial roles in dephosphorylating an array of substrates involved in pathways comprising receptor tyrosine kinases (RTKs) and immune receptors. This regulation maintains a delicate balance between the activation and inhibition of signal transduction, ensuring appropriate biological outcomes. In this review, we summarize research focused on elucidating the functions of SHP1 and SHP2 in hematopoiesis, immune regulation, and tumor biology, emphasizing recent findings related to cancer-driven immune evasion. Furthermore, we highlight the significant effects of SHP1 and SHP2 inhibitors in enhancing cancer treatment, specifically through the facilitation of chemotherapy and augmentation of immune activation.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"667-677"},"PeriodicalIF":18.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Lessons in longevity from blood stem cells under protein stress. 蛋白质压力下的造血干细胞对长寿的启示。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-07-29 DOI: 10.1016/j.tcb.2025.06.006
André Catic
{"title":"Lessons in longevity from blood stem cells under protein stress.","authors":"André Catic","doi":"10.1016/j.tcb.2025.06.006","DOIUrl":"10.1016/j.tcb.2025.06.006","url":null,"abstract":"<p><p>Blood stem cells are among the body's longest-living cells despite being highly vulnerable to proteotoxic damage, which accelerates their aging. To maintain protein homeostasis (proteostasis), hematopoietic stem cells (HSCs) employ mechanisms such as reduced translation rates, high chaperone activity, autophagy, and selective protein degradation. These strategies mitigate protein misfolding, maintain quiescence, and preserve regenerative potential. Disruptions in proteostasis can lead to the elimination of impaired HSCs through differentiation or apoptosis, ensuring the integrity of the stem cell pool. Due to the systemic impact of the blood on aging and its experimental and clinical accessibility, investigating HSC proteostasis provides insights into longevity and potential therapeutic strategies. This review examines emerging mechanistic links between proteostasis and HSC fate, concluding with unresolved questions and challenges of the current research.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":18.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Stem-like cells at the center of CD4 T cell differentiation. 干细胞是CD4 T细胞分化的中心。
IF 13 1区 生物学
Trends in Cell Biology Pub Date : 2025-07-15 DOI: 10.1016/j.tcb.2025.06.004
Maria A Cardenas, Haydn T Kissick
{"title":"Stem-like cells at the center of CD4 T cell differentiation.","authors":"Maria A Cardenas, Haydn T Kissick","doi":"10.1016/j.tcb.2025.06.004","DOIUrl":"https://doi.org/10.1016/j.tcb.2025.06.004","url":null,"abstract":"<p><p>CD4 T cells orchestrate immune responses through differentiation into specialized helper subsets. Traditionally, CD4 T cell differentiation is described as a linear process in which naïve CD4 T cells commit to distinct effector lineages upon activation. However, growing evidence challenging this paradigm has provoked considerable debate about CD4 T cell plasticity. This review describes the emerging concept of stem-like CD4 T cells and how they update our understanding of the fundamental mechanisms that regulate CD4 T cell differentiation. We discuss how stem-like CD4 T cells play a crucial role as precursor cells to distinct effector subsets and explore their implications in cancer, infections, and autoimmunity. Finally, we address how stem-like CD4 T cells might resolve long-standing questions about CD4 T cell plasticity, and propose alternative differentiation models that incorporate this population in chronic diseases.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Proteoglycans are protagonists in autophagy, lymphangiogenesis, and neurodegenerative diseases. 蛋白聚糖是自噬、淋巴管生成和神经退行性疾病的主角。
IF 13 1区 生物学
Trends in Cell Biology Pub Date : 2025-07-10 DOI: 10.1016/j.tcb.2025.06.002
Gabriel J Pascal, Sadie Kim, Christopher Xie, Dipon Mondal, Renato V Iozzo
{"title":"Proteoglycans are protagonists in autophagy, lymphangiogenesis, and neurodegenerative diseases.","authors":"Gabriel J Pascal, Sadie Kim, Christopher Xie, Dipon Mondal, Renato V Iozzo","doi":"10.1016/j.tcb.2025.06.002","DOIUrl":"10.1016/j.tcb.2025.06.002","url":null,"abstract":"<p><p>Proteoglycans (PGs) are specialized cell-surface and secreted proteins teeming with bioactivity. They have been the subject of fascinating research on autophagy, lymphangiogenesis, and neurodegenerative diseases. PG influence on autophagy extends to several disease domains, and their ability to alter autophagic processes has highlighted their suitability as therapeutic targets. PGs also display new functions by evoking protracted autophagy in lymphatic endothelial cells and inhibiting tumor and physiological lymphangiogenesis. The variable degree of PG sulfation and their ability to regulate growth-factor activities in the central nervous system has opened doors into novel therapeutic avenues including Alzheimer's and Parkinson's diseases. This review systematically integrates these diverse qualities of PGs while highlighting future directions towards clinical application.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Time as a danger signal promoting G1 arrest after mitosis. 时间是促进有丝分裂后G1停搏的危险信号。
IF 13 1区 生物学
Trends in Cell Biology Pub Date : 2025-07-07 DOI: 10.1016/j.tcb.2025.06.001
Luke J Fulcher, Caleb Batley, Tomoaki Sobajima, Francis A Barr
{"title":"Time as a danger signal promoting G1 arrest after mitosis.","authors":"Luke J Fulcher, Caleb Batley, Tomoaki Sobajima, Francis A Barr","doi":"10.1016/j.tcb.2025.06.001","DOIUrl":"https://doi.org/10.1016/j.tcb.2025.06.001","url":null,"abstract":"<p><p>Cell cycle checkpoints preventing the replication and inheritance of damaged DNA are crucial for maintaining genome stability and stopping the growth of damaged cells. Canonical checkpoints do this by preventing passage between cell cycle phases until damage has been repaired, or by promoting cell cycle exit. Herein we review checkpoint integration between cell cycle phases, specifically findings showing that extended spindle assembly checkpoint surveillance in mitosis is a danger signal triggering G1 cell cycle arrest. Evidence linking mitotic delays induced by activation of the spindle assembly checkpoint with positive and negative regulators of the G1 DNA damage checkpoint target p53 is discussed, with a focus on time-dependent changes to a p53-binding deubiquitinating complex USP28-53BP1 and the p53 ubiquitin-ligase mouse double minute homologue 2 (MDM2), respectively.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
The role of the immune tumor microenvironment in shaping metastatic dissemination, dormancy, and outgrowth. 免疫肿瘤微环境在形成转移性传播、休眠和生长中的作用。
IF 13 1区 生物学
Trends in Cell Biology Pub Date : 2025-07-04 DOI: 10.1016/j.tcb.2025.05.006
Garis Grant, Christina M Ferrer
{"title":"The role of the immune tumor microenvironment in shaping metastatic dissemination, dormancy, and outgrowth.","authors":"Garis Grant, Christina M Ferrer","doi":"10.1016/j.tcb.2025.05.006","DOIUrl":"https://doi.org/10.1016/j.tcb.2025.05.006","url":null,"abstract":"<p><p>The tumor microenvironment (TME) is a dynamic and complex ecosystem composed of cancer cells and diverse non-malignant cell types, including immune cells, fibroblasts, and endothelial cells. Once viewed as passive bystanders, these host cells are now recognized as active participants in tumor progression, especially during metastasis. The TME varies by organ, cancer type, and disease stage, and shapes the trajectory of cancer progression. Among the immune cells in the TME, macrophages, neutrophils, and T cells play especially crucial and context-dependent roles - either promoting or inhibiting metastatic spread depending on the tumor stage, immune cell phenotypic states, and interactions. In this review we focus on the multifaceted contributions of these key immune populations across the major stages of the metastatic cascade: initiation, survival in the circulation, dissemination, dormancy, and reactivation. These insights highlight the heterogeneity of the metastatic immune microenvironment and underscore the therapeutic potential of targeting macrophages, neutrophils, and T cells to combat metastatic disease.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
MDM4 exon skipping upon dysfunctional ribosome assembly. 核糖体组装失调时的 MDM4 外显子跳转。
IF 13 1区 生物学
Trends in Cell Biology Pub Date : 2025-07-01 Epub Date: 2024-11-07 DOI: 10.1016/j.tcb.2024.10.006
Jennifer Jansen, Matthias Dobbelstein
{"title":"MDM4 exon skipping upon dysfunctional ribosome assembly.","authors":"Jennifer Jansen, Matthias Dobbelstein","doi":"10.1016/j.tcb.2024.10.006","DOIUrl":"10.1016/j.tcb.2024.10.006","url":null,"abstract":"<p><p>Recent studies revealed how nucleolar stress enhances MDM4 exon skipping and activates p53 via the ribosomal protein L22 (RPL22; eL22). Tumor-associated L22 mutations lead to full-length MDM4 synthesis, overcoming tumor suppression by p53. This forum article explores how MDM4 splicing patterns integrate stress signaling to take p53-dependent cell fate decisions.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"544-547"},"PeriodicalIF":13.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Metabolism and mRNA translation: a nexus of cancer plasticity. 新陈代谢与 mRNA 翻译：癌症可塑性的纽带。
IF 13 1区 生物学
Trends in Cell Biology Pub Date : 2025-07-01 Epub Date: 2024-11-27 DOI: 10.1016/j.tcb.2024.10.009
Xinpu Tang, Kaixiu Li, Yuqing Wang, Stéphane Rocchi, Shensi Shen, Michael Cerezo
{"title":"Metabolism and mRNA translation: a nexus of cancer plasticity.","authors":"Xinpu Tang, Kaixiu Li, Yuqing Wang, Stéphane Rocchi, Shensi Shen, Michael Cerezo","doi":"10.1016/j.tcb.2024.10.009","DOIUrl":"10.1016/j.tcb.2024.10.009","url":null,"abstract":"<p><p>Tumors often face energy deprivation due to mutations, hypoxia, and nutritional deficiencies within the harsh tumor microenvironment (TME), and as an effect of anticancer treatments. This metabolic stress triggers adaptive reprogramming of mRNA translation, which in turn adjusts metabolic plasticity and associated signaling pathways to ensure tumor cell survival. Emerging evidence is beginning to reveal the complex interplay between metabolism and mRNA translation, shedding light on the mechanisms that synchronize ribosome assembly and reconfigure translation programs under metabolic stress. This review explores recent advances in our understanding of the coordination between metabolism and mRNA translation, offering insights that could inform therapeutic strategies targeting both cancer metabolism and translation, with the aim of disrupting cancer cell plasticity and survival.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"562-575"},"PeriodicalIF":13.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Endoplasmic reticulum (ER) protein degradation by ER-associated degradation and ER-phagy. 内质网蛋白通过内质网相关降解和内质网吞噬降解。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-07-01 Epub Date: 2025-02-04 DOI: 10.1016/j.tcb.2025.01.002
Shuangcheng Alivia Wu, Zexin Jason Li, Ling Qi
{"title":"Endoplasmic reticulum (ER) protein degradation by ER-associated degradation and ER-phagy.","authors":"Shuangcheng Alivia Wu, Zexin Jason Li, Ling Qi","doi":"10.1016/j.tcb.2025.01.002","DOIUrl":"10.1016/j.tcb.2025.01.002","url":null,"abstract":"<p><p>Protein misfolding and aggregation in the endoplasmic reticulum (ER) have been causally linked to a variety of human diseases. Two key pathways for eliminating misfolded proteins and aggregates in the ER are ER-associated degradation (ERAD) and ER-phagy, respectively. While both pathways have been well characterized biochemically, our understanding of their physiological relevance and significance remains limited. In recent years, significant advances have been made, including the generation and characterization of various knockout and knockin mouse models, the identification of human disease-associated or -causing variants, and insights into the coordination between ERAD and autophagy in physiological contexts. In this review, we summarize these advancements, highlighting the key roles of a highly conserved suppressor of lin-12-like-hydroxymethyl glutaryl-coenzyme A reductase degradation 1 (SEL1L-HRD1) protein complex of ERAD and ER-phagy in health and disease.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"576-591"},"PeriodicalIF":18.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
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