Molecules and CellsPub Date : 2025-09-01Epub Date: 2025-07-18DOI: 10.1016/j.mocell.2025.100255
Junsoo Oh, Yeseul Park, Shinae Park, Og-Geum Woo, Jae-Hoon Lee, Jung-Shin Lee, Taekyung Kim
{"title":"Phosphatase regulation in cell division: With emphasis on PP2A-B56.","authors":"Junsoo Oh, Yeseul Park, Shinae Park, Og-Geum Woo, Jae-Hoon Lee, Jung-Shin Lee, Taekyung Kim","doi":"10.1016/j.mocell.2025.100255","DOIUrl":"10.1016/j.mocell.2025.100255","url":null,"abstract":"<p><p>Protein phosphatase 2A-B56 (PP2A-B56) is a key regulator of mitosis, playing an essential role in maintaining chromosomal stability and ensuring the fidelity of cell division. As a component of the PP2A holoenzyme, the B56 regulatory subunit confers substrate specificity, primarily through interactions with the conserved LxxIxE motif on target proteins. This review highlights the molecular mechanisms by which PP2A-B56 regulates key processes in cell division, including chromosome cohesion and condensation, kinetochore-microtubule attachment, spindle assembly checkpoint silencing, and activation of the anaphase-promoting complex/cyclosome. In meiosis, PP2A-B56 safeguards centromeric cohesion and facilitates the transition between divisions, with recruitment strategies that differ across species. Recent studies also emphasize its role in protecting oocyte quality and fertility by maintaining chromosomal stability. Furthermore, the competition among multiple LxxIxE-containing substrates for PP2A-B56 binding introduces an additional layer of temporal and spatial regulation. Finally, we discuss how perturbations in PP2A-B56 activity contribute to chromosomal instability and tumorigenesis. Understanding of PP2A-B56's substrate recognition and regulatory dynamics provides a framework for therapeutic targeting in disorders involving defective cell division.</p>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":" ","pages":"100255"},"PeriodicalIF":6.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hyunjin Koo , Minah Jung , Sangwoo Lee , Sangjin Go , Yong-Min Kim
{"title":"Identification and application of bioparts for plant synthetic biology","authors":"Hyunjin Koo , Minah Jung , Sangwoo Lee , Sangjin Go , Yong-Min Kim","doi":"10.1016/j.mocell.2025.100273","DOIUrl":"10.1016/j.mocell.2025.100273","url":null,"abstract":"<div><div>Plant synthetic biology is an emerging field that combines bioinformatics, computational gene circuit design, and plant science. It has the potential to be applied in various areas, including the production of pharmaceuticals, vaccines, biofuels, and various biomaterials, including plant natural products. This review highlights recent advancements in plant synthetic biology, particularly in the development and application of biological parts such as promoters and terminators, which play a crucial role in precise gene expression regulation. Furthermore, this review clarified the identification and utilization of bidirectional promoters, which are essential for gene pyramiding, and the significance of maintaining a balance between promoter and terminator combinations for the stability of transgene expression. Furthermore, large-scale identification of promoters using Assay for Transposase-Accessible Chromatin using sequencing and Self-Transcribing Active Regulatory Region sequencing, as well as deep-learning-based models for predicting promoter regions and their transcriptional activity, are discussed. This review provides insights into the identification and application of bioparts in plant synthetic biology to achieve efficient and precise gene regulation.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 10","pages":"Article 100273"},"PeriodicalIF":6.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Enyoung Seo , Sooyeon Park , Inho Park , Jinhyuk Bhin
{"title":"Decoding genomic rearrangements for cancer driver discovery","authors":"Enyoung Seo , Sooyeon Park , Inho Park , Jinhyuk Bhin","doi":"10.1016/j.mocell.2025.100272","DOIUrl":"10.1016/j.mocell.2025.100272","url":null,"abstract":"<div><div>Somatically acquired genomic rearrangements are common genomic alterations that contribute to malignancy by altering the expression or activity of cancer-related genes in human cancer. Genomic rearrangements play a crucial role in tumor development by contributing to driver events in approximately 25% of cancer patients. Most rearrangements are nonrecurrent and lack functional impact. However, some rearrangements produce functional transcripts and act as cancer drivers that may be therapeutic targets. The growing availability of whole-genome and matched RNA-sequencing data from large patient cohorts offers tremendous opportunities to identify novel, clinically relevant drivers arising from genomic rearrangements. In this review, we summarize current knowledge of driver rearrangements as therapeutic targets and highlight recent discoveries of functional transcripts such as intergenic fusions generated by noncanonical rearrangements. We also discuss computational approaches to decode rearrangement patterns and leverage large-scale whole-genome data to discover novel drivers.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 11","pages":"Article 100272"},"PeriodicalIF":6.5,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gahbien Lee , Jiyeon Lee , Greg S.B. Suh , Yangkyun Oh
{"title":"Post ingestive systemic nutrient sensing for whole-body homeostasis","authors":"Gahbien Lee , Jiyeon Lee , Greg S.B. Suh , Yangkyun Oh","doi":"10.1016/j.mocell.2025.100271","DOIUrl":"10.1016/j.mocell.2025.100271","url":null,"abstract":"<div><div>Systemic nutrient sensing is a fundamental process that aligns nutrient availability with an organism’s metabolic demands. This mini-review explores nutrient sensors in the intestine, pancreas, portal vein, and the brain—organs that detect and convey nutrient status to other tissues via neuronal and hormonal signaling. Unlike oral taste receptors that sense external nutrient inputs, these nutrient sensors monitor post ingestive levels of macronutrients (carbohydrates, proteins, and lipids) and micronutrients (vitamins and essential trace elements such as calcium, magnesium, and zinc) within the body. We describe the specific mechanisms by which each organ discerns fluctuations in nutrient concentration and discuss how these signals integrate into endocrine and neural circuits to maintain whole-body nutrient balance. Finally, by comparing mammalian and invertebrate models such as <em>Drosophila</em>, we offer a comprehensive perspective on how organ-level nutrient sensing upholds metabolic homeostasis across diverse species.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 11","pages":"Article 100271"},"PeriodicalIF":6.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cover and caption","authors":"","doi":"10.1016/S1016-8478(25)00091-3","DOIUrl":"10.1016/S1016-8478(25)00091-3","url":null,"abstract":"","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 9","pages":"Article 100267"},"PeriodicalIF":6.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144879658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rationale and emerging evidence for microglial replacement in Alzheimer’s disease","authors":"Jee Yoon Bang , Yongjin Yoo","doi":"10.1016/j.mocell.2025.100265","DOIUrl":"10.1016/j.mocell.2025.100265","url":null,"abstract":"<div><div>Microglial biology in Alzheimer’s disease (AD) has become a major focus of investigation, aiming to define how these cells contribute to neurodegeneration and to develop new therapeutic strategies. Once regarded as passive responders, microglia are now recognized as active regulators of brain homeostasis, immune signaling, and synaptic remodeling. Their interactions with genetic risk variants and age-related changes are increasingly understood to play central roles in AD pathogenesis. In this mini-review, we summarize recent progress in identifying microglial contributions to AD through genetic and transcriptomic studies. We discuss how microglia respond to amyloid-β and tau pathology by shifting into diverse functional disease-associated states, which may either protect or harm the brain depending on context and disease stage. We also outline the rationale for targeting microglia through replacement strategies and review emerging approaches using circulation-derived myeloid cells (CDMCs), and human pluripotent stem cell–derived microglia-like cells. These replacement methods have shown potential to rectify microglial functions and modify AD-related pathology in preclinical models, offering a novel therapeutic direction for neurodegenerative diseases.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 10","pages":"Article 100265"},"PeriodicalIF":6.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yawen Jiang , Ligang Zhang , Yuandong Lin , Xiangxing Zhu , Tao Wang , Zhu Zhu , Yingshan Chen , Dongsheng Tang
{"title":"Iron metabolism dysregulation and ferroptosis: Emerging drivers in pulmonary fibrosis pathogenesis and therapy","authors":"Yawen Jiang , Ligang Zhang , Yuandong Lin , Xiangxing Zhu , Tao Wang , Zhu Zhu , Yingshan Chen , Dongsheng Tang","doi":"10.1016/j.mocell.2025.100264","DOIUrl":"10.1016/j.mocell.2025.100264","url":null,"abstract":"<div><div>Ferroptosis is an iron-dependent and regulated form of cell death, characterized by lipid peroxidation and oxidative stress. The progressive development of pulmonary fibrosis (PF) is closely linked to the ferroptosis pathway. Although the underlying mechanisms remain incompletely defined, this field has drawn intense research attention. Notable progress has been made in identifying ferroptosis-related metabolic pathways and key targets during PF development. In this review, we first summarize the basic regulation of iron metabolism in the human lung, iron metabolic imbalance, and the activation of ferroptosis. Second, we focus on elaborating the mechanistic connections between ferroptosis and PF, encompassing the clinical features, pathological manifestations, and core pathogenic mechanisms of PF, as well as the interplay between ferroptosis and 3 specific cell types in PF: alveolar epithelial cells, macrophages, and fibroblasts. Third, the research progress in the pharmacotherapy of PF is categorized into 3 categories: drugs already approved for PF and those under clinical trials; ferroptosis-targeted therapeutic strategies, including inhibitors, natural compounds, gene therapy, and combination strategies. This review, grounded in key metabolic pathways and therapeutic targets, systematically explores the complex relationships among iron metabolic disorders, ferroptosis, and PF progression. Our aim is to provide a theoretical and practical foundation for ferroptosis-targeted PF treatment.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 10","pages":"Article 100264"},"PeriodicalIF":6.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jamin Ku , Eunjin Jeong , Jeong-Ryeol Gong , Kwang-Hyun Cho , Chang Ohk Sung , Seok-Hyung Kim
{"title":"Identification of a unique subpopulation of mucosal fibroblasts in colorectal cancer with tumor-restraining characteristics","authors":"Jamin Ku , Eunjin Jeong , Jeong-Ryeol Gong , Kwang-Hyun Cho , Chang Ohk Sung , Seok-Hyung Kim","doi":"10.1016/j.mocell.2025.100263","DOIUrl":"10.1016/j.mocell.2025.100263","url":null,"abstract":"<div><div>While tumor-restraining cancer-associated fibroblasts (Tr-CAFs) have been investigated in various cancers, their existence in colorectal cancer remains unexplored. We performed a comprehensive analysis of diverse colorectal cancer datasets, including single-cell RNA-seq/ATAC-seq data from colorectal samples, TCGA RNA-seq, and histological samples. We identified a fibroblast subpopulation uniquely expressing ADAMDEC1, CXCL14, EDNRB, and PROCR, strongly associated with favorable patient outcomes, implicating their role as Tr-CAFs. Pseudotime trajectory analysis suggested these cells as terminally differentiated mucosal fibroblasts. Pathway analysis indicated that this subpopulation was significantly associated with tumor-suppressive functions, such as reduced extracellular matrix secretion, augmented immune response, and enhanced responsiveness to immunotherapy. Single-cell ATAC-seq analysis revealed that this putative Tr-CAF subset exhibited unique epigenetic profiles characterized by superenhancer-regulated tumor-suppressive genes, thereby supporting its identity as a stable lineage rather than a transient phenotypic state induced by external stimuli. Immunohistochemistry showed that key markers identifying this putative Tr-CAF subset—CXCL14, ADAMDEC1, EDNRB, and PROCR—were predominantly localized to fibroblasts within normal colonic mucosa and less frequently in cancer-associated fibroblasts (CAFs). Their expression levels exhibited statistically significant associations with favorable clinicopathological indicators, including prolonged disease-free survival. Notably, ADAMDEC1 expression in CAFs was significantly correlated with T-cell infiltration within the tumor microenvironment. In conclusion, our investigation elucidates the characteristics and clinical relevance of Tr-CAFs in colorectal cancer, suggesting novel avenues for targeted anti-CAF therapy.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 10","pages":"Article 100263"},"PeriodicalIF":6.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jing Zhang , Seong Eun Lee , Jiyeon Yoon , Bon Jeong Ku , Junyoung O. Park , Da Hyun Kang , Jun Young Heo , Yea Eun Kang
{"title":"Multifaceted role of serine hydroxymethyltransferase in health and disease","authors":"Jing Zhang , Seong Eun Lee , Jiyeon Yoon , Bon Jeong Ku , Junyoung O. Park , Da Hyun Kang , Jun Young Heo , Yea Eun Kang","doi":"10.1016/j.mocell.2025.100262","DOIUrl":"10.1016/j.mocell.2025.100262","url":null,"abstract":"<div><div>Serine hydroxymethyltransferase (SHMT) is a key enzyme in 1-carbon metabolism, a biochemical pathway critical for cellular growth, proliferation, and survival. One-carbon metabolism integrates the folate and methionine cycles to produce essential intermediates necessary for nucleotide synthesis, methylation reactions, and redox homeostasis. SHMT exists in 2 isoforms, SHMT1, which is localized in the cytoplasm, and SHMT2, which is localized in the mitochondria. SHMT1 and SHMT2 have distinct yet complementary functions. Both are involved in serine and glycine metabolism, ensuring a continuous supply of the 1-carbon units required for biosynthetic and epigenetic processes. SHMT dysregulation has been implicated in cancer progression and metabolic disorders, including cardiovascular diseases, diabetes, and neurological abnormalities. In cancer, the abnormal expression of SHMT has been associated with tumor growth, metabolic reprogramming, and treatment resistance, and has also been shown to correlate with poor patient outcomes. Considering its critical role in both cancer and metabolic diseases, SHMT has emerged as a potential therapeutic target in cancer. Recent studies have shown that SHMT inhibitors can reduce tumor proliferation and restore metabolic homeostasis. This review provides a comprehensive overview of the role of SHMT in the regulation of metabolic pathways and its role in tumor progression and metabolic diseases. In this review, we aimed to highlight the therapeutic potential of targeting SHMT and offer insights into the development of innovative treatment strategies in oncology and metabolic medicine. These insights support the hypothesis that targeting SHMT, particularly isoform-specific inhibition, may provide novel therapeutic avenues in both oncology and metabolic medicine.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 9","pages":"Article 100262"},"PeriodicalIF":6.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}