Biochimica et biophysica acta. Molecular cell research最新文献

{"title":"Heat shock protein 70 regulates m6A modification in response to heat shock in esophageal squamous cell carcinoma.","authors":"Bin Du, Jia Wang, Jun Ma, Pu Wang","doi":"10.1016/j.bbamcr.2025.120027","DOIUrl":"https://doi.org/10.1016/j.bbamcr.2025.120027","url":null,"abstract":"<p><p>Heat shock has been known to induce hyperplasia in esophageal epithelial cells. It is widely considered as a crucial risk factor in the initiation and development of esophageal squamous cell carcinoma (ESCC), yet our understanding of the underlying mechanisms remains limited. The m6A modification of mRNA plays a role in mediating several cellular processes and is critical during cell stress. Our study revealed that the severely lacking of m6A 'writer' components of ESCC cells exhibit higher apoptosis rates and slower recovery after heat shock. After normalization using mRNA expression profiles, 91.07 % of significantly changed m6A modifications aligned with corresponding mRNA abundance changes, with no evidence of over-modification, while the increase in m6A modification of 8.92 % of heat-shock associated genes far exceeded the increase in mRNA (hyper - m6A modification), and A/U rich motifs were commonly observed in the 3'UTR of these genes. Inside the nucleus, the binding of HSP70s in m6A writer complex promote the hyper - m6A modification in specific mRNAs after heat shock. The stronger nuclear localization of HSP70 in ESCC tissues correlates with a poor prognosis for the patients. In conclusion, our research revealed that the nuclear HSP70 protein could bind to the METTL3/14 complex and regulate mRNA's m6A modification. Our results provide a new perspective for research into how HSP70 protein regulates mRNA stability and suggests a new direction for the comprehensive prevention and treatment of ESCC.</p>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":" ","pages":"120027"},"PeriodicalIF":4.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"USP47 enhances NRP1-mediated angiogenesis to promote gastric cancer progression\" [Volume 1872, Issue 7, October 2025, 120004].","authors":"Wei Chen, Huizhi Wang, Haitao Sun, Junbo Zuo, Pengcheng Jiang, Wen Feng, Zhenhua Huang","doi":"10.1016/j.bbamcr.2025.120025","DOIUrl":"https://doi.org/10.1016/j.bbamcr.2025.120025","url":null,"abstract":"","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":" ","pages":"120025"},"PeriodicalIF":4.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"XCL1: a multifunctional chemokine with metamorphic properties and therapeutic potential after injury to the nervous system – review","authors":"Agata Ciechanowska,&nbsp;Joanna Mika","doi":"10.1016/j.bbamcr.2025.120028","DOIUrl":"10.1016/j.bbamcr.2025.120028","url":null,"abstract":"<div><div>XC Motif Chemokine Ligand 1 (XCL1, known as lymphotactin), acting via XCR1, is a member of the chemokine family which includes molecules with chemotactic functions. However, subsequent years of research on this chemokine, while simultaneously exploring and understanding the complexity of the processes taking place in living organisms, have revealed a plethora of interesting information about its properties. This review aims to combine the current knowledge on the properties of XCL1 under pathological conditions, particularly in neuropathy. We wanted to draw attention to the unusual properties of XCL1 that have not yet been considered, such as its metamorphic properties and its mutual connections with glycosaminoglycans and integrin subunit alpha 9 (ITGA9). Furthermore, given the well-documented roles of XCL1 in the coordination of homeostatic and immune responses, we anticipate that a comprehensive understanding of the molecular interactions regulating XCL1 binding and activation of its receptors may facilitate the development of novel drugs targeting XCR1 or ITGA9 in various diseases. This point of view may be of great importance in the future for the modulation of systems related to this chemokine for therapeutic applications. This review aims to outline new areas of interest, to break out of following old patterns and dead ends and to sketch further research paths.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 7","pages":"Article 120028"},"PeriodicalIF":4.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone deacetylase 11 regulates stress granule formation to promote endothelial-to-mesenchymal transition in atherosclerosis","authors":"Lingxuan Ren ,&nbsp;Yizhen Liu ,&nbsp;Danli Chen ,&nbsp;Xiaoyu Rong ,&nbsp;Jiazheng Wen ,&nbsp;Zihan Zheng ,&nbsp;Lifang Chen ,&nbsp;Jianyu He ,&nbsp;Weirong Wang ,&nbsp;Rong Lin","doi":"10.1016/j.bbamcr.2025.120026","DOIUrl":"10.1016/j.bbamcr.2025.120026","url":null,"abstract":"<div><div>Histone deacetylase 11 (HDAC11) is the only member of the class IV HDAC family and is involved in cardiovascular diseases (CVDs). Stress granule (SG) is non-membranous cytoplasmic foci induced by various stress conditions, and also has emerged as a key player for CVDs. However, the regulatory role of HDAC11 in SG formation and underlying mechanism during atherosclerosis remain elusive. Therefore, we aimed to investigate the effect of HDAC11 on SG in ApoE^−/− mice fed with a HFD and HUVECs induced by H₂O₂. Firstly, we found that the expression levels of SG core proteins G3BP1/2 and HDAC11 were increased in the aorta of ApoE^−/− mice fed with a HFD for 12w via analyses of Western blotting, Real-time PCR and immunofluorescence staining. In addition, endothelial-to-mesenchymal transition (EndMT) was occurred in the aorta of ApoE^−/− mice. Then, in vitro experiments demonstrated that treatment of HUVECs with H₂O₂ resulted in SG formation, HDAC11 upregulation, and EndMT occurrence. Furthermore, knockdown of HDAC11 by siRNA significantly attenuated SG formation and EndMT activation in HUVECs induced by H₂O₂. Silencing of HDAC11 suppressed H₂O₂-induced EndMT activation in HUVECs, which may be attributed to increased acetylation of G3BP1/2 and the consequent impairment of SG formation. Further studies found that suppression of SG formation not only facilitated the expression of endothelial markers, but also decreased the levels of mesenchymal cell markers. Taken together, these findings identified that HDAC11 may regulate SG formation to promote EndMT in atherosclerosis, targeting SG could represent a novel therapeutic strategy for addressing the underlying mechanisms of atherosclerosis.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 7","pages":"Article 120026"},"PeriodicalIF":4.6,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The thylakoidal Tat receptor complex appears as a homo-trimeric TatC core with three associated TatB subunits","authors":"Matthias Reimers ,&nbsp;Mario Jakob ,&nbsp;Ralf Bernd Klösgen","doi":"10.1016/j.bbamcr.2025.120024","DOIUrl":"10.1016/j.bbamcr.2025.120024","url":null,"abstract":"<div><div>The Twin-arginine translocation (Tat) machinery, which is found in most cellular membranes containing a respiratory or photosynthetic electron transport chain, is characterized by its unique ability to catalyze membrane transport of folded proteins without impairing the membrane potential. In plant thylakoids, Tat machinery consists of three subunits, TatA, TatB, and TatC, with the latter two, TatB and TatC, forming membrane-integral multimeric TatBC receptor complexes. Here we have analyzed the stability and the subunit composition of these complexes after solubilization of thylakoids with the mild detergent digitonin as well as after additional affinity-purification. Employing different detergent combinations and/or heat treatment (40 °C) followed by BN-PAGE and Western analysis we could identify four distinct Tat complexes with apparent molecular masses ranging from approximately 230 kDa to 620 kDa. Treatment of the largest Tat complex with either heat or detergents like DDM or Triton X-114 led to its stepwise breakdown into the three smaller complexes resulting from the successive release of TatB subunits from a relatively stable TatC core complex. From these data we postulate that the fully assembled, physiologically active TatBC receptor complex consists of a stable, trimeric TatC core to which three TatB subunits are bound independently from each other.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 7","pages":"Article 120024"},"PeriodicalIF":4.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"M6A-mediated uc003pes.1 stability regulates proliferation and migration of human coronary artery smooth muscle cells via scaffolding STAT1 and USP10","authors":"Rongli Jiang ,&nbsp;Qiaowei Jia ,&nbsp;Chengcheng Li ,&nbsp;Shu He ,&nbsp;Hanxiao Zhou ,&nbsp;Mengmeng Ren ,&nbsp;Lanyu Liang ,&nbsp;Enzhi Jia","doi":"10.1016/j.bbamcr.2025.120023","DOIUrl":"10.1016/j.bbamcr.2025.120023","url":null,"abstract":"<div><h3>Background</h3><div>The <em>uc003pes.1</em> has been identified as a potential diagnostic biomarker for coronary artery disease (CAD) and is associated with the risk of CAD. However, the precise function and intricate mechanism of <em>uc003pes.1</em> in CAD remain elusive.</div></div><div><h3>Methods</h3><div>To elucidate the underlying mechanism we employed various techniques including RNA pull-down assays coupled with mass spectrometry analysis, RIP, RNA MeRIP, as well as luciferase reporter gene analysis.</div></div><div><h3>Results</h3><div>Overexpression of uc003pes.1 suppressed the proliferation and migration of HCASMCs. The upregulation of uc003pes.1 can be attributed to m6A modification mediated by the methylase RBM15. In terms of downstream mechanisms, uc003pes.1 acts as a molecular scaffold facilitating the interaction between STAT1 and the USP10, thereby impeding ubiquitination degradation of STAT1 and promoting phosphorylation levels at Tyr701 and Ser727, ultimately influencing HCASMCs' proliferation and migration.</div></div><div><h3>Conclusion</h3><div>Our study has discovered, for the first time, that uc003pes.1, regulated by m6A modification, functions as a molecular scaffold for STAT1 and USP10. This interaction plays a crucial role in regulating the proliferation and migration of HCASMCs, thereby offering novel insights into the diagnosis and treatment of CAD.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 7","pages":"Article 120023"},"PeriodicalIF":4.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GRK5 regulates mitotic progression and promotes resistance against anti-mitotic agents in a CDK1 and AKT1 dependent manner","authors":"Nusrat Nabi ,&nbsp;Syed Qaaifah Gillani ,&nbsp;Marjan Fatima ,&nbsp;Misbah Un Nisa ,&nbsp;Zarka Sarwar ,&nbsp;Sameer Ahmed Bhat ,&nbsp;Irfana Reshi ,&nbsp;Shareen Bashir ,&nbsp;Fazl Q Parray ,&nbsp;Shaida Andrabi","doi":"10.1016/j.bbamcr.2025.120020","DOIUrl":"10.1016/j.bbamcr.2025.120020","url":null,"abstract":"<div><div>G protein receptor kinase 5 (GRK5) is a serine/threonine protein kinase that belongs to the family of G protein receptor kinases (GRKs), which are important regulators of G protein-coupled receptor (GPCR) functions. GRK5 regulates signaling by binding to various receptors on the plasma membrane or by regulating transcription within the nucleus. It also has been found to critically regulate several physiological processes including vascular remodelling, invasion, metastasis and migration of the cells. Although its role in cancer progression and metastasis is known, its role in cell division, and particularly in mitosis has not been investigated much. Here, we report that GRK5 is an important mitotic protein and is regulated by well-known cellular proteins that have a critical role in cell cycle regulation, especially mitosis. In particular, we show that GRK5 is regulated by two key players of mitosis, AKT1 and CDK1, which regulate GRK5 by interacting with it. We also provide evidence that GRK5 protein levels fluctuate throughout the cell cycle and reach their maximum during mitosis. Further, we report that overexpression of GRK5 promotes resistance against cell death that is induced by polyomavirus small T (PolST) antigen and different chemotherapeutic drugs including paclitaxel. Additionally, we found that GRK5 levels are upregulated in colorectal cancers supporting a potential role in tumor progression. Our findings thus add GRK5 to the growing list of mitotic kinases, which play a role in the regulation of cell cycle and promotion of drug resistance in cancer.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 7","pages":"Article 120020"},"PeriodicalIF":4.6,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, characterization and size-dependent cytotoxicity of magnesium ammonium phosphate hexahydrate crystals of different sizes on renal epithelial cells","authors":"Run-Min Tan ,&nbsp;Xin-Yi Tong ,&nbsp;Wen-Xuan Dai,&nbsp;Jia-Yi Zhang,&nbsp;Jian-Ming Ouyang","doi":"10.1016/j.bbamcr.2025.120022","DOIUrl":"10.1016/j.bbamcr.2025.120022","url":null,"abstract":"<div><div>Magnesium ammonium phosphate hexahydrate (MAP) crystals with sizes of 98.5 ± 20.6 nm, 310 ± 67 nm, 1.12 ± 0.34 μm, and 3.23 ± 0.90 μm were synthesized and characterized. These crystals can cause damage to renal tubular epithelial cells (HK−2), which is manifested by crystal-induced cell morphological changes, cell viability, a decrease in superoxide dismutase and mitochondrial membrane potential. In addition, there were crystal-induced increases in reactive oxygen species, lactate dehydrogenase, and malondialdehyde levels, as well as phosphatidylserine ectropion. That is, MAP crystals can lead to cell necrosis and apoptosis, and promote the release of inflammatory cytokines IL-18 and IL-6. The cytotoxicity of MAP crystals has a size effect, that is, the cytotoxicity is: MAP-100 nm &gt; MAP-300 nm &gt; MAP-1 μm &gt; MAP-3 μm. The factors enhancing the cytotoxicity of MAP include small size, large specific surface area, and a more negative crystal surface zeta potential. Nano-crystal MAP-100 nm mainly causes cell death by inducing extensive cell necrosis. When the larger-sized MAP-300 nm, MAP-1 μm and MAP-3 μm crystals acted on HK-2 cells, cell necrosis, apoptosis and autophagy occurred simultaneously. Investigating the relationship between MAP crystal size and cytotoxicity may provide insights into elucidating the mechanism of MAP stone (struvite) formation and preventing its occurrence.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 7","pages":"Article 120022"},"PeriodicalIF":4.6,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deubiquitinases in metabolic diseases, fibrosis and cancer of the liver","authors":"Ananya Thakur,&nbsp;Kateryna Kubaichuk,&nbsp;Thomas Kietzmann","doi":"10.1016/j.bbamcr.2025.120021","DOIUrl":"10.1016/j.bbamcr.2025.120021","url":null,"abstract":"<div><div>Obesity is a key driver of the progression from metabolic dysfunction-associated steatotic liver disease (MASLD), to metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, and hepatocellular carcinoma (HCC). Excess adiposity and elevated circulating fatty acids disrupt metabolic, inflammatory, and signaling pathways, creating conditions permissive for hepatic injury, inflammation, fibrogenesis, and carcinogenesis. One of the mechanisms that regulates these pathways is ubiquitylation, a post-translational modification that controls protein degradation and cellular signaling. Deubiquitinases (DUBs) counterbalance this process by removing ubiquitin chains, thereby maintaining cellular homeostasis.</div><div>This review examines the role of DUBs in obesity-induced MASLD progression, focusing on how dysregulated DUB expression affects insulin signaling, lipogenesis, inflammation, and oxidative stress. While DUBs have been extensively studied in cancer and metabolic syndrome, their therapeutic potential in obesity-related MASH, liver fibrosis, and HCC has not been fully explored.</div><div>By synthesizing clinical and experimental evidence, we highlight DUBs as promising precision medicine tools for both patient stratification and therapeutic intervention. This review emphasizes the critical need for further translational research to develop DUB-targeted strategies for early intervention in MASLD progression.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 7","pages":"Article 120021"},"PeriodicalIF":4.6,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144623698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of mitochondrial quality control through autophagic pathway in familial Alzheimer's disease","authors":"Adriana Limone ,&nbsp;Clelia Di Napoli ,&nbsp;Giusy De Rosa ,&nbsp;Silvia Bagnoli ,&nbsp;Antonella Izzo ,&nbsp;Claudio Procaccini ,&nbsp;Giuseppe Matarese ,&nbsp;Benedetta Nacmias ,&nbsp;Antonio Lavecchia ,&nbsp;Daniela Sarnataro","doi":"10.1016/j.bbamcr.2025.120019","DOIUrl":"10.1016/j.bbamcr.2025.120019","url":null,"abstract":"<div><div>Autophagy is a highly conserved cellular catabolic process recognized as an essential pathway for the maintenance of cellular homeostasis. Growing evidence implicates autophagic dysfunction in the pathogenesis of several neurodegenerative disorders, including Alzheimer's disease (AD), thus its modulation might represent an interesting therapeutic tool. Searching for a compound that stimulates autophagic pathway, led us to identify the inhibitor of RPSA receptor, NSC47924. In this study, we show that, NSC47924 down-modulated Akt-mTOR-axis pathway, the master regulator of autophagy, which was abnormally hyperactivated in fibroblasts from genetic AD-affected patients. Consistently, by monitoring the conversion of LC3, we found that inhibition of RPSA enhanced and restored the compromised autophagic flux. Moreover, by qRT-PCR analysis we found that inhibitor treatment upregulated the expression of autophagy-linked genes.</div><div>Importantly, AD-affected fibroblasts exhibited massive mitochondrial network fragmentation and mitophagy defects, which were restored through the stimulation of autophagy induced by RPSA inhibition. Consistent with an efficient elimination of dysfunctional mitochondria, we found that the turnover of both the mitophagy regulators PINK1 and Parkin and the autophagic receptors p62, NDP52, OPTN, was modulated, thus restoring a highly interconnected organelle's network. In addition, the improvement of mitochondrial morphology correlated with a functional recovery, as assessed by Seahorse analysis and mitochondrial ROS production evaluation. Collectively, our findings suggest that RPSA inhibition stimulates an autophagic pathway promoting the efficient removal of damaged mitochondria, favouring the recovery of cellular homeostasis, and counteracting crucial AD pathogenic mechanisms.</div></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1872 7","pages":"Article 120019"},"PeriodicalIF":4.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}