{"title":"Role of expression quantitative trait loci (eQTL) in understanding genetic mechanisms underlying common complex diseases.","authors":"Sung Eun Hong, Murim Choi, Jeongha Lee","doi":"10.1016/j.mocell.2025.100256","DOIUrl":"https://doi.org/10.1016/j.mocell.2025.100256","url":null,"abstract":"<p><p>Attaining a complete understanding of the genetic architecture underlying common complex traits is challenging due to the substantial contributions of non-genetic factors and the involvement of numerous influencing genes. Genome-wide association studies (GWAS) have identified novel variants associated with such traits, but our understanding of the molecular genetic mechanisms underlying those associations remains limited. Additionally, variants without significant associations from GWAS can influence gene expression, contributing to individual-level variation in traits. This review summarizes the evolution, advancements in, and practical applications of eQTL analysis. Recent large-scale expression quantitative trait (eQTL) studies, often at the single-cell level, provide an opportunity to explain how at least some GWAS variants behave and to elucidate the mechanisms underlying individual-level variations. This approach can further be utilized to identify novel drug targets that are tailored to individuals harboring specific genotypes.</p>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":" ","pages":"100256"},"PeriodicalIF":3.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675303","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}
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":"https://doi.org/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 (SAC) silencing, and activation of the anaphase-promoting complex/cyclosome (APC/C). 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":3.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cover and caption","authors":"","doi":"10.1016/S1016-8478(25)00082-2","DOIUrl":"10.1016/S1016-8478(25)00082-2","url":null,"abstract":"","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 8","pages":"Article 100258"},"PeriodicalIF":3.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657190","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}
Hyun-Oh Gu, Seung Wan Noh, Ok-Hee Kim, Byung-Chul Oh
{"title":"Crucial Roles of Calcium ATPases and Phosphoinositides: Insights into Pathophysiology and Therapeutic Strategies.","authors":"Hyun-Oh Gu, Seung Wan Noh, Ok-Hee Kim, Byung-Chul Oh","doi":"10.1016/j.mocell.2025.100254","DOIUrl":"https://doi.org/10.1016/j.mocell.2025.100254","url":null,"abstract":"<p><p>Calcium (Ca²⁺) serves as a pivotal intracellular messenger, influencing a diverse array of cellular processes, including muscle contraction, neurotransmission, and hormone secretion. It also plays a critical role in the regulation of gene expression. Intracellular Ca²⁺ levels are stringently controlled and maintained within a narrow physiological range, primarily by plasma membrane Ca<sup>2+</sup>-ATPases, sarco/endoplasmic reticulum Ca<sup>2+</sup>-ATPases, and secretory pathway Ca<sup>2+</sup>-ATPases. These ATPases orchestrate the influx, efflux, and sequestration of Ca²⁺ across cellular compartments, thereby ensuring cellular functionality and survival. This review delves into the intricate interplay between Ca²⁺ and phosphoinositides (PIPs), essential lipid signaling molecules that modulate Ca<sup>2+</sup>-ATPase activities and link Ca²⁺ signaling to a wide range of cellular functions. By examining the molecular dynamics of Ca<sup>2+</sup>-ATPases and their regulatory interactions with PIPs, we discuss their roles under both physiological and pathological conditions, highlighting how disturbances in these interactions contribute to disease. Furthermore, we explore the potential of targeting these Ca²⁺ regulatory mechanisms as a therapeutic strategy for diseases characterized by Ca²⁺ dysregulation, providing insights into future research directions and clinical applications.</p>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":" ","pages":"100254"},"PeriodicalIF":3.7,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626726","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}
Xiang Li , Bo Chen , Jiajing Zhou , Chunling Li , Yue Yu , Erdi Zhao , Xingli Wu , Changzhu Jin , Minjing Li , Jiankai Feng , Leilei Lin , Yancun Yin
{"title":"Tumor-derived CD84 promotes growth of acute myeloid leukemia cells via regulating nonhomologous DNA end-joining pathway","authors":"Xiang Li , Bo Chen , Jiajing Zhou , Chunling Li , Yue Yu , Erdi Zhao , Xingli Wu , Changzhu Jin , Minjing Li , Jiankai Feng , Leilei Lin , Yancun Yin","doi":"10.1016/j.mocell.2025.100253","DOIUrl":"10.1016/j.mocell.2025.100253","url":null,"abstract":"<div><div>CD84, a member of the signaling lymphocyte activation molecule immunoglobulin superfamily, has been identified as playing a significant role in regulating various immune cell activities. However, its intrinsic role in cancer cells remains largely unknown. We aim to explore the direct role of CD84 in acute myeloid leukemia (AML) progression and to clarify the underlying molecular mechanisms involved in nonhomologous end-joining (NHEJ) repair. Herein, we found that CD84 is frequently upregulated in various types of AML and leukemia initiation cells (LICs)-enriched cells. Knockdown or blocking of CD84 significantly inhibits the growth and induces the apoptosis of AML cells. Moreover, knockdown of <em>CD84</em> significantly delays AML progression and prolongs the survival of the xenografted mice in vivo. Mechanistically, CD84 promotes the expression of NHEJ core factors by recruiting SAP and activating the AKT signaling pathway. Knockdown of <em>CD84</em> inhibits NHEJ repair in AML cells via regulating the expression of NHEJ core factors, including <em>PRKDC</em>, <em>LIG4</em>, <em>XRCC5</em>, and <em>DCLRE1C.</em> Subsequently, this leads to double-strand breaks accumulation and cell apoptosis. Importantly, CD84 is required for the proliferation and self-renewal of human LICs. In conclusion, CD84 plays important roles in AML growth and progression through promoting NHEJ repair. Targeting CD84 may be a potential approach for inhibiting AML development and eliminating LICs.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 9","pages":"Article 100253"},"PeriodicalIF":3.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601023","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":"Cyclotides as novel plant-derived scaffolds for orally active cyclic peptide therapeutics","authors":"Youbong Hyun","doi":"10.1016/j.mocell.2025.100252","DOIUrl":"10.1016/j.mocell.2025.100252","url":null,"abstract":"<div><div>Cyclotides are a group of plant-derived small peptides, characterized by a head-to-tail cyclic backbone and 3 conserved cysteine knots. The unique structure endows cyclotides with exceptional chemical stability and intrinsic cell-penetrating capacities, allowing them to serve as orally active agents for host defense. These properties also position cyclotides as ideal scaffolds for the design of novel edible drugs. This review provides a comprehensive overview of the discovery, distribution, and evolutionary divergence of cyclotides in flowering plants, while also discussing their classification and applications in structure-based engineering for various purposes. Additionally, recent advancements in the biological and pharmaceutical activities of both naturally occurring and synthetic “designer” cyclotides are summarized. The complexities of the cyclotide biosynthetic pathway have posed challenges for their synthesis in non-native organisms. Thus, the article concludes by exploring the latest strategies for large-scale cyclotide production in plants, highlighting <em>Viola</em> species as rich sources for future cyclotide engineering.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 9","pages":"Article 100252"},"PeriodicalIF":3.7,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575904","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":"A practical guide to ordering C. elegans strains for biological research","authors":"Yeon-Ji Park , Kyeong Min Moon , Kyuhyung Kim","doi":"10.1016/j.mocell.2025.100251","DOIUrl":"10.1016/j.mocell.2025.100251","url":null,"abstract":"<div><div><em>Caenorhabditis elegans</em> (<em>C. elegans</em>) is a widely used model organism in biological research, contributing to our understanding of fundamental processes in areas such as development, neurobiology, and aging. Accessing the appropriate <em>C. elegans</em> strains is crucial for conducting experiments and advancing scientific knowledge. This work provides a comprehensive overview of the process of ordering <em>C. elegans</em>.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 9","pages":"Article 100251"},"PeriodicalIF":3.7,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564963","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}
SeokGyeong Choi , Sojung Ha , Donald J. Wolfgeher , Jee Won Kim , Young-Hyun Go , Hyuk-Jin Cha , Gyu-Un Bae , Stephen J. Kron , Woo-Young Kim
{"title":"N-Terminal deleted isoforms of E3 ligase RNF220 are ubiquitously expressed and required for mouse muscle differentiation","authors":"SeokGyeong Choi , Sojung Ha , Donald J. Wolfgeher , Jee Won Kim , Young-Hyun Go , Hyuk-Jin Cha , Gyu-Un Bae , Stephen J. Kron , Woo-Young Kim","doi":"10.1016/j.mocell.2025.100250","DOIUrl":"10.1016/j.mocell.2025.100250","url":null,"abstract":"<div><div>Four isoform peptides of the novel E3 ligase ring finger protein 220 (RNF220) have been identified in humans. However, all of the previous studies have predominantly focused on isoform 1 (the full-length form), which consists of 566 amino acids. Here, we show that a shorter isoform, which is 308 amino acids lacking most of the N-terminus (human isoform 4; mouse isoform 3; ΔN-RNF220), is the predominant and ubiquitously expressed variant that warrants functional investigation. Both isoform 1 and ΔN-RNF220 are expressed in the brain; however, ΔN-RNF220 is the major isoform expressed in all other tissues in mice. Consistently, H3K4me3 ChIP-seq data from ENCODE reveal that the transcription start site for ΔN-RNF220 demonstrates broader and stronger activity across human tissues than that of isoform 1. ΔN-RNF220 produces 2 peptides (4a and 4b) through alternative translation initiation, with isoform 4b displaying distinct subcellular localization, subnuclear structures and interaction with a nuclear protein WDR5. Notably, during embryonic stem cell differentiation into neural stem cells, isoform 1 expression increases, whereas ΔN-RNF220 expression decreases. In murine myoblasts, ΔN-RNF220 is the sole expressed isoform and is required for MyoD and myogenin expression, as well as for muscle differentiation. Our findings highlight ΔN-RNF220 as the ubiquitously and highly expressed variant, likely playing a fundamental role across tissues while exhibiting functional differences from isoform 1. These results emphasize the critical importance of ΔN-RNF220 in future studies investigating the biological functions of RNF220.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 9","pages":"Article 100250"},"PeriodicalIF":3.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560537","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":"Brief guide to Caenorhabditis elegans imaging and quantification","authors":"Hyemin Min, Gyutae Park, Seung-Jae V. Lee","doi":"10.1016/j.mocell.2025.100249","DOIUrl":"10.1016/j.mocell.2025.100249","url":null,"abstract":"<div><div><em>Caenorhabditis elegans</em> is a powerful model organism for fluorescence imaging to study gene regulation and cellular biomarkers. This concise MiniResource introduces essential imaging techniques for live and fixed <em>C. elegans</em>, sample preparations, microscopy, and common applications. We also outline basic image analysis workflows using open-source software. This guideline serves as a practical resource for researchers who seek implementing fluorescence imaging with <em>C. elegans</em>.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 9","pages":"Article 100249"},"PeriodicalIF":3.7,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540965","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}