Pub Date : 2025-10-01Epub Date: 2025-09-18DOI: 10.1016/S1016-8478(25)00103-7
{"title":"Cover and caption","authors":"","doi":"10.1016/S1016-8478(25)00103-7","DOIUrl":"10.1016/S1016-8478(25)00103-7","url":null,"abstract":"","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 10","pages":"Article 100279"},"PeriodicalIF":6.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145105733","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}
Pub Date : 2025-10-01Epub Date: 2025-09-16DOI: 10.1016/j.mocell.2025.100266
Yuan Shao , Wanli Ren , Hao Dai , Fangli Yang , Xiang Li , Shaoqiang Zhang , Junsong Liu , Xiaobao Yao , Qian Zhao , Xin Sun , Zhiwei Zheng , Chongwen Xu
{"title":"Corrigendum to “SKP2 contributes to AKT activation by ubiquitination degradation of PHLPP1, impedes autophagy, and facilitates the survival of thyroid carcinoma” [Molecules and Cells Volume 46, Issue 6, June 2023, 360-373]","authors":"Yuan Shao , Wanli Ren , Hao Dai , Fangli Yang , Xiang Li , Shaoqiang Zhang , Junsong Liu , Xiaobao Yao , Qian Zhao , Xin Sun , Zhiwei Zheng , Chongwen Xu","doi":"10.1016/j.mocell.2025.100266","DOIUrl":"10.1016/j.mocell.2025.100266","url":null,"abstract":"","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 10","pages":"Article 100266"},"PeriodicalIF":6.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081086","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}
Pub Date : 2025-09-01Epub Date: 2025-07-18DOI: 10.1016/j.mocell.2025.100256
Sung Eun Hong, Murim Choi, Jeongha Lee
Attaining a complete understanding of the genetic architecture underlying common complex traits is challenging due to the substantial contributions of nongenetic 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 expression quantitative trait loci analysis. Recent large-scale expression quantitative trait loci 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.
{"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":"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 nongenetic 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 expression quantitative trait loci analysis. Recent large-scale expression quantitative trait loci 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":6.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357303/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-07-11DOI: 10.1016/j.mocell.2025.100254
Hyun-Oh Gu , Seung Wan Noh , Ok-Hee Kim , Byung-Chul Oh
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 Ca2+-ATPases, sarco-/endoplasmic reticulum Ca2+-ATPases, and secretory pathway Ca2+-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, essential lipid signaling molecules that modulate Ca2+-ATPase activities and link Ca²⁺ signaling to a wide range of cellular functions. By examining the molecular dynamics of Ca2+-ATPases and their regulatory interactions with phosphoinositides, 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.
{"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":"10.1016/j.mocell.2025.100254","url":null,"abstract":"<div><div>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, 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 phosphoinositides, 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.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 9","pages":"Article 100254"},"PeriodicalIF":6.5,"publicationDate":"2025-09-01","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}
Pub 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
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.
{"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}
Pub Date : 2025-09-01Epub Date: 2025-07-02DOI: 10.1016/j.mocell.2025.100251
Yeon-Ji Park , Kyeong Min Moon , Kyuhyung Kim
Caenorhabditis elegans (C. elegans) 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 C. elegans strains is crucial for conducting experiments and advancing scientific knowledge. This work provides a comprehensive overview of the process of ordering C. elegans.
{"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":"2025-09-01","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}
Pub Date : 2025-09-01Epub Date: 2025-07-01DOI: 10.1016/j.mocell.2025.100250
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
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.
{"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":"2025-09-01","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}
Pub Date : 2025-09-01Epub Date: 2025-07-28DOI: 10.1016/j.mocell.2025.100262
Jing Zhang , Seong Eun Lee , Jiyeon Yoon , Bon Jeong Ku , Junyoung O. Park , Da Hyun Kang , Jun Young Heo , Yea Eun Kang
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.
{"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":"2025-09-01","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}
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