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Navigating AKT-ivity across cellular compartments. 通过细胞区室导航akt活性。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-08-28 DOI: 10.1016/j.tcb.2025.08.001
Jichao Sun, Mo Chen
{"title":"Navigating AKT-ivity across cellular compartments.","authors":"Jichao Sun, Mo Chen","doi":"10.1016/j.tcb.2025.08.001","DOIUrl":"https://doi.org/10.1016/j.tcb.2025.08.001","url":null,"abstract":"<p><p>Phosphoinositide (PIP)-mediated AKT signaling is essential for cellular homeostasis because it orchestrates crucial processes such as metabolism, survival, proliferation, and motility. Dysregulation of this pathway drives various pathologies, particularly cancer. Although cytosolic activation of AKT has been extensively studied, its emerging roles in the nucleus have gained attention over the past decade. The complexities of AKT compartmentalization and associated functional mechanisms remain largely unexplored. At the plasma membrane, AKT activation occurs at specialized microdomains and cell-cell junctions where it influences polarity, adhesion, and migration. In endosomes, PIPs coordinate intracellular trafficking and cytoskeletal organization with AKT signaling. Protein scaffolds refine AKT signal specificity by assembling complexes. In the nucleus, AKT interacts with the p53-PIP signalosome and specific kinases to regulate oncogenesis and chemoresistance. This review explores PIP-driven spatial regulation of AKT across cellular compartments, emphasizing its role in cellular responses and oncogenesis. Understanding AKT compartmentalization mechanisms provides valuable insights into cancer biology and novel therapeutic strategies.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":18.1,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980124","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 nutrient stress in DNA damage. 营养应激在DNA损伤中的作用。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-08-26 DOI: 10.1016/j.tcb.2025.08.006
Jiali Jin, Ping Wang
{"title":"The role of nutrient stress in DNA damage.","authors":"Jiali Jin, Ping Wang","doi":"10.1016/j.tcb.2025.08.006","DOIUrl":"https://doi.org/10.1016/j.tcb.2025.08.006","url":null,"abstract":"<p><p>Cells are constantly exposed to various stresses, including nutrient deprivation and genotoxic stress, which dynamically interact with cellular sensing pathways to influence metabolism, gene expression, and homeostasis. The integration of nutrient-sensing mechanisms and DNA damage response pathways is critical in cancer progression. While individual processes are well-characterized, their cross-regulatory mechanisms are just beginning to emerge. Deciphering the interplay between nutrient stress and DNA damage is crucial for elucidating the mechanisms underlying cellular responses to stress and developing therapeutic strategies for various diseases, including cancer. This review highlights the relationship between nutrient stress and DNA damage, especially its underlying sensing pathway and cell fate determination.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":18.1,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980105","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
Decoding the language of PLK1 docking motifs and activation mechanisms. 解码PLK1对接基序的语言和激活机制。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-08-08 DOI: 10.1016/j.tcb.2025.07.004
Arianna Esposito-Verza, Andrea Musacchio, Duccio Conti
{"title":"Decoding the language of PLK1 docking motifs and activation mechanisms.","authors":"Arianna Esposito-Verza, Andrea Musacchio, Duccio Conti","doi":"10.1016/j.tcb.2025.07.004","DOIUrl":"https://doi.org/10.1016/j.tcb.2025.07.004","url":null,"abstract":"<p><p>Polo-like kinase 1 (PLK1) phosphorylates a plethora of different substrates to regulate key cell cycle processes that include, among others, mitotic entry, chromosome condensation, nuclear envelope breakdown, centrosome maturation, spindle assembly and chromosome biorientation, cytokinesis, and the deposition of the specialized centromere histone CENP-A. Addressing the exact spatial and temporal control of PLK1 activity in these processes and its dynamic interplay with protein phosphatases that counteract mitotic phosphorylation, most notably PP1 and PP2A, has proven especially puzzling. In this review, we focus on the main unknowns in the area of human PLK1 regulation, exploring more specifically an emerging concept that master docking sites, including newly discovered noncanonical motifs, trigger initial local activation of PLK1 that promotes subsequent localized spreading of phosphorylation.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":18.1,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812714","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
NADH reductive stress drives metabolic reprogramming. NADH还原性应激驱动代谢重编程。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-08-05 DOI: 10.1016/j.tcb.2025.07.005
Ronghui Yang, Zihao Guo, Binghui Li
{"title":"NADH reductive stress drives metabolic reprogramming.","authors":"Ronghui Yang, Zihao Guo, Binghui Li","doi":"10.1016/j.tcb.2025.07.005","DOIUrl":"https://doi.org/10.1016/j.tcb.2025.07.005","url":null,"abstract":"<p><p>Cellular metabolism is intricately regulated by redox signaling, with the NADH/NAD<sup>+</sup> couple serving as a central hub. Emerging evidence reveals that NADH reductive stress, marked by NADH accumulation, is not merely a passive byproduct of metabolic dysfunction but an active regulatory signal driving metabolic reprogramming. In this Review, we synthesize recent advances in understanding NADH reductive stress, including its origins, regulatory mechanism, and manipulation. We examine its broad impact on cellular metabolism, its interplay with oxidative and energy stress, and its pathogenic roles in a range of diseases. By integrating these findings, we propose NADH reductive stress as a master regulator for metabolic reprogramming and highlight new avenues for mechanistic exploration and therapeutic intervention.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":""},"PeriodicalIF":18.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796250","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
Single cell lipid biology. 单细胞脂质生物学。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-08-01 Epub Date: 2025-01-14 DOI: 10.1016/j.tcb.2024.12.002
Agostina Crotta Asis, Antonino Asaro, Giovanni D'Angelo
{"title":"Single cell lipid biology.","authors":"Agostina Crotta Asis, Antonino Asaro, Giovanni D'Angelo","doi":"10.1016/j.tcb.2024.12.002","DOIUrl":"10.1016/j.tcb.2024.12.002","url":null,"abstract":"<p><p>Lipids are major cell constituents endowed with astonishing structural diversity. The pathways responsible for the assembly and disposal of different lipid species are energetically demanding, and genes encoding lipid metabolic factors and lipid-related proteins comprise a sizable fraction of our coding genome. Despite the importance of lipids, the biological significance of lipid structural diversity remains largely obscure. Recent technological developments have enabled extensive lipid analysis at the single cell level, revealing unexpected cell-cell variability in lipid composition. This new evidence suggests that lipid diversity is exploited in multicellularity and that lipids have a role in the establishment and maintenance of cell identity. In this review, we highlight the emerging concepts and technologies in single cell lipid analysis and the implications of this research for future studies.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"651-666"},"PeriodicalIF":18.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017031","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
Peroxisomes are underappreciated organelles hijacked by viruses. 过氧物酶体是被病毒劫持的细胞器，但人们对它的认识不足。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-08-01 Epub Date: 2024-12-11 DOI: 10.1016/j.tcb.2024.11.006
Marie Villares, Lucile Espert, Coralie F Daussy
{"title":"Peroxisomes are underappreciated organelles hijacked by viruses.","authors":"Marie Villares, Lucile Espert, Coralie F Daussy","doi":"10.1016/j.tcb.2024.11.006","DOIUrl":"10.1016/j.tcb.2024.11.006","url":null,"abstract":"<p><p>Peroxisomes are cellular organelles that are crucial for metabolism, stress responses, and healthy aging. They have recently come to be considered as important mediators of the immune response during viral infections. Consequently, various viruses target peroxisomes for the purpose of hijacking either their biogenesis or their functions, as a means of replicating efficiently, making this a compelling research area. Despite their known connections with mitochondria, which have been the object of considerable research on account of their role in the innate immune response, less is known about peroxisomes in this context. In this review, we explore the evolving understanding of the role of peroxisomes, highlighting recent findings on how they are exploited by viruses to modulate their replication cycle.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"678-689"},"PeriodicalIF":18.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819961","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
Decoding human cardiovascular development and disease through single-cell transcriptomic and epigenomic profiling. 通过单细胞转录组和表观基因组分析解码人类心血管发育和疾病。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-08-01 Epub Date: 2025-06-09 DOI: 10.1016/j.tcb.2025.05.001
Logan Dunkenberger, Daniel Y Li, Ioannis Karakikes, Thomas Quertermous
{"title":"Decoding human cardiovascular development and disease through single-cell transcriptomic and epigenomic profiling.","authors":"Logan Dunkenberger, Daniel Y Li, Ioannis Karakikes, Thomas Quertermous","doi":"10.1016/j.tcb.2025.05.001","DOIUrl":"10.1016/j.tcb.2025.05.001","url":null,"abstract":"<p><p>Concomitant progress in the fields of microfluidics, microscale molecular biology, next-generation sequencing, and analytical methods for whole transcriptomic datasets has transformed our ability to understand complex cellular state changes at the single-cell level. New cell types have been discovered and cell transition states and intermediate phenotypes have been characterized across diverse developmental and disease contexts. More recently, integrating transcriptomic and epigenomic data has dramatically extended our understanding of transcriptional regulons and gene regulatory networks (GRNs) that determine gene expression and individual cellular phenotypes. Applied to cardiac biology, combined transcriptomic and epigenomic profiling has allowed the characterization of the developmental trajectories and molecular mechanisms that give rise to the diverse cell lineages of the adult heart and contribute to the pathogenesis of genetic diseases. In this review, we present the latest methodological innovations, discuss the computational strategies for multiomic data integration, and highlight how these advances are reshaping our undestanding of heart development and disease mechanisms.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"690-701"},"PeriodicalIF":18.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267959","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
ATRX loss induces lineage plasticity and squamous-like phenotype to promote colorectal cancer metastasis. ATRX缺失诱导谱系可塑性和鳞状样表型，促进结直肠癌转移。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-08-01 Epub Date: 2025-07-24 DOI: 10.1016/j.tcb.2025.07.003
Yali Chen, Gaili Ji, Peishan Hu, Rong Xiang
{"title":"ATRX loss induces lineage plasticity and squamous-like phenotype to promote colorectal cancer metastasis.","authors":"Yali Chen, Gaili Ji, Peishan Hu, Rong Xiang","doi":"10.1016/j.tcb.2025.07.003","DOIUrl":"10.1016/j.tcb.2025.07.003","url":null,"abstract":"<p><p>Colorectal cancer (CRC) metastasis is driven by phenotypic plasticity beyond classic epithelial-mesenchymal transition (EMT), including non-canonical lineages such as squamous-like phenotypes. Their regulatory mechanisms and clinical significance remain unclear. In the current issue of Nature, Cammareri et al. identified ATRX loss as a driver of multilineage plasticity, including squamous-like characteristics, linked to increased metastasis and poor clinical outcomes in CRC.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"637-640"},"PeriodicalIF":18.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719165","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
Age-associated changes in transcriptional elongation and their effects on homeostasis. 年龄相关的转录延伸变化及其对体内平衡的影响。
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-08-01 Epub Date: 2024-12-19 DOI: 10.1016/j.tcb.2024.11.005
Argyris Papantonis, Adam Antebi, Linda Partridge, Andreas Beyer
{"title":"Age-associated changes in transcriptional elongation and their effects on homeostasis.","authors":"Argyris Papantonis, Adam Antebi, Linda Partridge, Andreas Beyer","doi":"10.1016/j.tcb.2024.11.005","DOIUrl":"10.1016/j.tcb.2024.11.005","url":null,"abstract":"<p><p>Cellular homeostasis declines with age due to the declining fidelity of biosynthetic processes and the accumulation of molecular damage. Yet, it remains largely elusive how individual processes are affected during aging and what their specific contribution to age-related functional decline is. This review discusses a series of recent publications that has shown that transcription elongation is compromised during aging due to increasing DNA damage, stalling of RNA polymerase II (RNAPII), erroneous transcription initiation in gene bodies, and accelerated RNAPII elongation. Importantly, several of these perturbations likely arise from changes in chromatin organization with age. Thus, taken together, this work establishes a network of interlinked processes contributing to age-related decline in the quantity and quality of RNA production.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"645-650"},"PeriodicalIF":18.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873582","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
Is clathrin a membrane fission protein? 网格蛋白是一种膜裂变蛋白吗？
IF 18.1 1区 生物学
Trends in Cell Biology Pub Date : 2025-08-01 Epub Date: 2025-04-19 DOI: 10.1016/j.tcb.2025.03.005
Ling-Gang Wu, Lisi Wei, Michael M Kozlov
{"title":"Is clathrin a membrane fission protein?","authors":"Ling-Gang Wu, Lisi Wei, Michael M Kozlov","doi":"10.1016/j.tcb.2025.03.005","DOIUrl":"10.1016/j.tcb.2025.03.005","url":null,"abstract":"<p><p>Membrane fission is thought to involve helix-forming proteins to constrict the Ω-shaped profile's neck. Recent studies suggest that membrane pit-coating proteins, especially clathrin, may also mediate fission via polymerization on the Ω-profile's base or head to generate neck constriction, which underlies various endocytic modes previously attributed as clathrin (Ω-profile head) independent.</p>","PeriodicalId":56085,"journal":{"name":"Trends in Cell Biology","volume":" ","pages":"641-644"},"PeriodicalIF":18.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027583","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
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