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E2F8 facilitates malignant phenotypes of muscle-invasive bladder cancer via increasing MCM7 expression. E2F8 通过增加 MCM7 的表达促进肌肉浸润性膀胱癌恶性表型的形成。
IF 2.4 3区 生物学
Biochemistry and Cell Biology Pub Date : 2025-01-01 Epub Date: 2024-11-27 DOI: 10.1139/bcb-2024-0083
Li-Yun Liu, Liang Tian, Ling-Huan Gao, Hai-Jun Cui, Xue-Mei Li, Yue-Hong Li
{"title":"E2F8 facilitates malignant phenotypes of muscle-invasive bladder cancer via increasing MCM7 expression.","authors":"Li-Yun Liu, Liang Tian, Ling-Huan Gao, Hai-Jun Cui, Xue-Mei Li, Yue-Hong Li","doi":"10.1139/bcb-2024-0083","DOIUrl":"10.1139/bcb-2024-0083","url":null,"abstract":"<p><p>E2F transcription factor 8 (E2F8) is an important regulator of the cell cycle. In this study, we first assessed the expression of E2F8 in bladder cancer and examined its effects in the malignant phenotypes of bladder cancer cell lines. We found that E2F8 was upregulated in bladder cancer tissues, and the increased expression was positively associated with higher clinical stage. E2F8 knockdown suppressed bladder cancer cell proliferation, accompanied by the performance of G1 phase arrest and the upregulated Cyclin D1 protein expression. The migrative and invasive capability was reduced in E2F8-depleted bladder cancer cells. Cisplatin resistance is an important cause of bladder cancer relapse. E2F8 downregulation facilitated cisplatin-induced apoptosis of bladder cancer cells. MCM7 is regulated by E2F and has been shown to participate in bladder cancer. There was a positive correlation between E2F8 and MCM7 expression in bladder cancer. We confirmed that E2F8 bound to the promoter region of MCM7 and activated MCM7 transcription. MCM7 overexpression abrogated the suppressive effects of E2F8 knockdown on malignant phenotypes of bladder cancer cells. We also demonstrated that E2F8 knockdown suppressed bladder cancer progression in vivo. In conclusion, we verify that E2F8 functioned in bladder cancer, and might exert its function via MCM7.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-14"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725360","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}
引用次数: 0
Emerging roles of High Mobility Group A (HMGA) family members in nuclear organization. 高流动性A族(HMGA)家族成员在核组织中的新角色。
IF 2.1 3区 生物学
Biochemistry and Cell Biology Pub Date : 2025-01-01 DOI: 10.1139/bcb-2025-0100
Manpreet Singh, Thatchawan Thanasupawat, Thomas Klonisch, Sabine Hombach-Klonisch
{"title":"Emerging roles of High Mobility Group A (HMGA) family members in nuclear organization.","authors":"Manpreet Singh, Thatchawan Thanasupawat, Thomas Klonisch, Sabine Hombach-Klonisch","doi":"10.1139/bcb-2025-0100","DOIUrl":"10.1139/bcb-2025-0100","url":null,"abstract":"<p><p>Chromatin remodeling plays a crucial role in gene expression. Chromatin architecture is governed by the interaction of a variety of proteins and transcription factors, including histones and non-histone chromatin-binding factors. Non-histone proteins, such as high mobility group-associated proteins High Mobility Group A (HMGA), are key players in this process. They do not have transcriptional activity per se but comprise flexible intrinsically disordered proteins (IDP) that interact with nucleosomes to change the compaction of chromatin at enhancers and promoters, thereby modulating the process of transcription. HMGA proteins have attained significant attention for their role in the regulation of gene expression during development, cell differentiation and in cellular senescence. Their molecular interactions are controlled by posttranslational modifications which determine nucleoprotein complex formation and function. This review highlights the role of HMGA proteins in nuclear organization, at telomeres and centromere regions and in senescence-associated heterochromatin foci and links these spatiotemporal chromatin architectural functions to the molecular domain structure of HMGA proteins in fine-tuning dynamic chromatin states.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-14"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145399584","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}
引用次数: 0
Solution NMR structure and NMR-based molecular backbone dynamics of UbKEKS: a ubiquitin variant encoded in the UBB4 pseudogene with emerging specific and new functions. UbKEKS的溶液核磁共振结构和基于核磁共振的分子骨架动力学:UBB4伪基因编码的泛素变体,具有新兴的特异性和新功能。
IF 2.1 3区 生物学
Biochemistry and Cell Biology Pub Date : 2025-01-01 DOI: 10.1139/bcb-2025-0166
Patrick Delattre, Danny Létourneau, Anna Meller, Xavier Roucou, François-Michel Boisvert, Pierre Lavigne
{"title":"Solution NMR structure and NMR-based molecular backbone dynamics of Ub<sup>KEKS</sup>: a ubiquitin variant encoded in the UBB4 pseudogene with emerging specific and new functions.","authors":"Patrick Delattre, Danny Létourneau, Anna Meller, Xavier Roucou, François-Michel Boisvert, Pierre Lavigne","doi":"10.1139/bcb-2025-0166","DOIUrl":"10.1139/bcb-2025-0166","url":null,"abstract":"<p><p>Recently, proteomics analyses using databases of unannotated ORFs revealed that ubiquitin (Ub) variants can be encoded and expressed from pseudogenes. One such pseudogene, UBBP4, produces Ub<sup>KEKS</sup>, which contains four substitutions (Q2K, K33E, Q49K, and N60S) relative to canonical Ub. Unlike Ub, Ub<sup>KEKS</sup> does not promote proteasomal degradation through K48 linkages and instead modifies a distinct set of proteins. To elucidate the structural basis of this divergence, we solved the NMR solution structure of Ub<sup>KEKS</sup> and characterized its backbone dynamics by 15N-relaxation. While Ub<sup>KEKS</sup> retains the overall helix-grip fold, we observed significant rearrangements and amplified motions in residues governing the Ub pincer mode, a conformational switch that determines whether UIMs engage the canonical I44 interface or the α1-β3 edge. Specifically, Q2K and K33E cooperate to enhance motions on both fast (ps-ns) and slow (µs-ms) timescales within α1, the β1-β2 loop, and β5-regions central to pincer mode regulation. In addition, Q49K, adjacent to I44, perturbs UIM recognition and likely interferes with K48 chain formation and binding to the proteasomal receptor S5a. Collectively, our findings identify structural and dynamical determinants that explain Ub<sup>KEKS's</sup> distinct substrate profile and inability to target proteins for degradation.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-10"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211451","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}
引用次数: 0
Galanthamine promotes neuronal differentiation and neurite outgrowth of neural progenitor/stem cells by up-regulating IGF-2. 加兰他敏通过上调IGF-2促进神经祖细胞/干细胞的神经元分化和神经突生长。
IF 2.1 3区 生物学
Biochemistry and Cell Biology Pub Date : 2025-01-01 DOI: 10.1139/bcb-2025-0058
Xia Jiang, Liming Wu, Rong Zhou, Miaohua Quan, Xiaoliang Xiang
{"title":"Galanthamine promotes neuronal differentiation and neurite outgrowth of neural progenitor/stem cells by up-regulating IGF-2.","authors":"Xia Jiang, Liming Wu, Rong Zhou, Miaohua Quan, Xiaoliang Xiang","doi":"10.1139/bcb-2025-0058","DOIUrl":"10.1139/bcb-2025-0058","url":null,"abstract":"<p><p>Galanthamine, an alkaloid derived from the Amaryllidaceae family, serves as an acetylcholinesterase inhibitor. Due to its central cholinergic properties, this compound is being actively studied as a potential treatment for Alzheimer's disease. However, the broader scope of its biological effects remains poorly understood. In this study, we explored the therapeutic potential of galanthamine in promoting neuronal differentiation and enhancing neurite outgrowth in neural stem and progenitor cells (NSPCs). Our detailed analysis demonstrated notable changes in neuronal morphology and complexity during maturation following galanthamine exposure. Notably, the compound significantly increased the proportion of neurons with multiple neurites, indicating its ability to stimulate neurite formation and foster the development of complex neuronal networks. Furthermore, galanthamine treatment led to a marked rise in the number of mature-appearing neurons, distinguished by elongated and intricate dendrites, highlighting its potential to enhance neural plasticity and repair mechanisms. Importantly, we also identified that galanthamine facilitates neuronal differentiation in NSPCs by up-regulating the insulin-like growth factor 2 signaling pathway. Collectively, these findings provide valuable insights into galanthamine's role in Alzheimer's disease and emphasize its promise as a therapeutic agent for this neurodegenerative disorder.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-9"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940709","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}
引用次数: 0
CDHR5 splice isoform cooperation promotes apical targeting of the brush border cadherin. CDHR5剪接异构体的合作促进了刷状缘钙粘蛋白的顶端靶向。
IF 2.1 3区 生物学
Biochemistry and Cell Biology Pub Date : 2025-01-01 DOI: 10.1139/bcb-2025-0044
Samaneh Matoo, Prashun Acharya, Sadika T J Tonu, Jasvinder Bharaj, Ashwini Mudaliyar, Katherine Holmes, Nicole Roeser, Natalie Hill, Basmala Touny, Regan VanderPol, Scott W Crawley
{"title":"CDHR5 splice isoform cooperation promotes apical targeting of the brush border cadherin.","authors":"Samaneh Matoo, Prashun Acharya, Sadika T J Tonu, Jasvinder Bharaj, Ashwini Mudaliyar, Katherine Holmes, Nicole Roeser, Natalie Hill, Basmala Touny, Regan VanderPol, Scott W Crawley","doi":"10.1139/bcb-2025-0044","DOIUrl":"10.1139/bcb-2025-0044","url":null,"abstract":"<p><p>Cadherin-related family member 5 (CDHR5) is an adhesion molecule that is highly enriched in the microvilli found on the surface of transporting epithelial cells of the gut and kidney. CDHR5 localizes to the distal tips of these microvilli as part of an adhesion complex that drives assembly of microvilli into a cohesive apical brush border, a hallmark feature of polarized transporting epithelial cells. Loss of CDHR5 correlates with poor prognosis of colon cancer patients, while forced over-expression of CDHR5 in colorectal cancer cell lines blocks their ability to form tumors in mice. Despite acting as an apparent tumor suppressor, how CDHR5 targets to the apical domain of transporting epithelial cells to exert its tumor suppressor effects is poorly understood. Here, we show that CDHR5 is expressed as three dominant splice isoforms in intestinal epithelial cells that differ only in the presence and composition of a membrane-proximal extracellular mucin-like domain. When present in the CDHR5 ectodomain, this mucin-like domain restricted targeting of the cadherin to apical microvilli. Importantly, we show that this restriction could be bypassed through apparent hetero-oligomer formation between the splice isoforms that have the mucin-like domain and the isoform that does not.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-11"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741058","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}
引用次数: 0
Bovine lactoferrin suppresses the proliferation of endometriotic stromal cells via the PI3K/Akt/mTOR pathway. 牛乳铁蛋白通过PI3K/Akt/mTOR通路抑制子宫内膜异位症基质细胞的增殖。
IF 2.1 3区 生物学
Biochemistry and Cell Biology Pub Date : 2025-01-01 DOI: 10.1139/bcb-2025-0014
Akiko Nakamura, Yuji Tanaka, Shunichiro Tsuji, Tsukuru Amano, Akie Takebayashi, Akimasa Takahashi, Ayako Inatomi, Tetsuro Hanada, Takashi Murakami
{"title":"Bovine lactoferrin suppresses the proliferation of endometriotic stromal cells via the PI3K/Akt/mTOR pathway.","authors":"Akiko Nakamura, Yuji Tanaka, Shunichiro Tsuji, Tsukuru Amano, Akie Takebayashi, Akimasa Takahashi, Ayako Inatomi, Tetsuro Hanada, Takashi Murakami","doi":"10.1139/bcb-2025-0014","DOIUrl":"10.1139/bcb-2025-0014","url":null,"abstract":"<p><p>The most common medical therapy for endometriosis suppresses ovulation, which is a barrier for patients planning pregnancy. To address this issue, we focused on the cell proliferation-suppressing effects of lactoferrin, which reportedly in various malignant tumours. Despite being a benign disease, endometriotic cells have similar characteristics to malignant tumours, which may be involved in its onset and progression. Endometriotic and endometrial stromal cells were obtained from patients with endometriosis. After culture with 1 mg/mL of bovine lactoferrin, cell proliferation was significantly suppressed in endometriotic stromal cells compared to controls, but this remained unchanged in endometrial stromal cells. Bovine lactoferrin also significantly increased the number of endometriotic stromal cells in the G0/G1 phase and significantly decreased those in the S phase, and suppressed the protein expression of phosphorylated-AKT, phosphorylated-mTOR, phosphorylated-S6K, and cyclin D1. Bovine lactoferrin inhibits the transition from the G1 to the S phase by suppressing the PI3K/Akt/mTOR pathway and reducing the synthesis of cyclin D1, thereby arresting the cell cycle at the G1 phase. Bovine lactoferrin suppressed the proliferation of endometriotic stromal cells without suppressing the proliferation of endometrial stromal cells. Lactoferrin, which allows for pregnancy and lactation during administration, has potential as a novel therapeutic candidate for endometriosis.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-8"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257224","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}
引用次数: 0
Identification of features and differences in PD-1 inhibitor-associated myocarditis and acute myocardial infarction using proteomic analysis: a clinical and preclinical study. 利用蛋白质组学分析鉴定PD-1抑制剂相关心肌炎和急性心肌梗死的特征和差异:一项临床和临床前研究
IF 2.1 3区 生物学
Biochemistry and Cell Biology Pub Date : 2025-01-01 DOI: 10.1139/bcb-2025-0170
Yuxi Luo, Yali Yi, Fujuan Zeng, Zhiqin Lu, Wenjie Xu, Haiyang Fang, Peng Xu, Anwen Liu, Zhimin Zeng
{"title":"Identification of features and differences in PD-1 inhibitor-associated myocarditis and acute myocardial infarction using proteomic analysis: a clinical and preclinical study.","authors":"Yuxi Luo, Yali Yi, Fujuan Zeng, Zhiqin Lu, Wenjie Xu, Haiyang Fang, Peng Xu, Anwen Liu, Zhimin Zeng","doi":"10.1139/bcb-2025-0170","DOIUrl":"10.1139/bcb-2025-0170","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs)-related myocarditis, a severe complication characterized by elevated cardiac troponin I, poses significant clinical challenges in distinguishing it from acute myocardial infarction (AMI). Our study aimed to identify plasma protein biomarkers that differentiate ICIs-myocarditis from AMI. Plasma samples from 5 ICIs-myocarditis patients (with paired baseline and diagnosis samples) and 5 angiography-confirmed AMI patients, matched for age, gender, smoking history, and pre-existing heart disease, were analyzed using label-free liquid chromatography-mass spectrometry proteomics. A total of 1521 plasma proteins were identified, with 1325 quantifiable. Proteomic profiling revealed differentially expressed proteins (DEPs) in ICIs-myocarditis associated with myocardial contraction, proteasome activity, NF-κB signaling, immunoregulation, and amino acid metabolism. Through validation in animal models of ICIs-myocarditis and AMI, two plasma proteins-MYOM3 (myomesin 3) and galectin-1 (LGALS1)-were identified as potential biomarkers linked to the onset of ICIs-related myocarditis. Further validation using expanded clinical cohorts confirmed their differential expression. These findings highlight MYOM3 and galectin-1 as promising biomarkers for distinguishing ICIs-related myocarditis from AMI, providing insights for clinical diagnosis and mechanistic research into immune-related cardiotoxicity.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-15"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854375","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}
引用次数: 0
Targeting PINK1 using phytochemicals: exploring molecular insights into Parkinson's disease therapeutics. 利用植物化学物质靶向PINK1:探索帕金森病治疗的分子见解。
IF 2.1 3区 生物学
Biochemistry and Cell Biology Pub Date : 2025-01-01 DOI: 10.1139/bcb-2024-0280
Saranya Nallusamy, Selva Babu Selvamani, Chakkarai Sathyaseelan, Divya Selvakumar, Rashmi Panigrahi
{"title":"Targeting PINK1 using phytochemicals: exploring molecular insights into Parkinson's disease therapeutics.","authors":"Saranya Nallusamy, Selva Babu Selvamani, Chakkarai Sathyaseelan, Divya Selvakumar, Rashmi Panigrahi","doi":"10.1139/bcb-2024-0280","DOIUrl":"10.1139/bcb-2024-0280","url":null,"abstract":"<p><p>Parkinson's disease (PD) is one of the most commonly affecting neurodegenerative disorder prevalent in our society. The inherited autosomal recessive PD/parkinsonism occurs due to mutations in six genes including, the gene for PTEN (phosphatase and tensin homologue)-induced putative kinase1 (PINK1). The pathophysiology and development of disorders associated with the mitochondria occur simultaneously with the dysregulation of PINK1. The activation/regulation of PINK1 through autophagy regulators can reduce PD condition. This study focused on exploring the possibility of 2062 phytochemicals as autophagy regulators. <i>In silico</i> docking and simulation studies are performed to identify their binding with the PINK1. Our studies highlight the phytochemicals like Proanthocyanidin A-6, Withanolide Q, and pseudo-ginsenoside F11 that showed higher binding energy and stable interactions during the course of simulation. This study opens avenues for testing these compounds as positive modulators of PINK1 kinase activity using <i>in vitro</i> and <i>in vivo</i> methods and use of these compounds as phytotherapeutic for the treatment of PD.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-55"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582946","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}
引用次数: 0
Zyxin directly binds to chromosomal DNA and is linked with mitochondrial integrity and apoptosis. Zyxin直接与染色体DNA结合,并与线粒体完整性和凋亡有关。
IF 2.1 3区 生物学
Biochemistry and Cell Biology Pub Date : 2025-01-01 DOI: 10.1139/bcb-2025-0125
M Quadir Siddiqui, Marcin W Wojewodzic, Shridhar Sanghvi, Higor Sette Pereira, Gunjan Vasudeva, Kieran Meadows, Rutu Prajapati, Mitchell Geeraert, Maulik D Badmalia, Raymond J Owens, Neil A Hotchin, Harpreet Singh, Trushar R Patel
{"title":"Zyxin directly binds to chromosomal DNA and is linked with mitochondrial integrity and apoptosis.","authors":"M Quadir Siddiqui, Marcin W Wojewodzic, Shridhar Sanghvi, Higor Sette Pereira, Gunjan Vasudeva, Kieran Meadows, Rutu Prajapati, Mitchell Geeraert, Maulik D Badmalia, Raymond J Owens, Neil A Hotchin, Harpreet Singh, Trushar R Patel","doi":"10.1139/bcb-2025-0125","DOIUrl":"10.1139/bcb-2025-0125","url":null,"abstract":"<p><p>Human zyxin is a key component of the focal adhesion complex, playing a role in mediating cell-cell adhesion and cytoskeletal dynamics. Moreover, zyxin shuttles between the cytoplasm and the nucleus, where it contributes to regulating gene expression. Although identified over 30 years ago, zyxin's nuclear functions, particularly in relation to cancer, remain largely unexplored. In this study, we profiled zyxin binding to chromosomal DNA using metastatic prostate carcinoma PC3M cells as a model. Our ChIP-Seq results revealed that zyxin binds to chromosomal DNA, with mitochondrial pseudogenes as the primary targets. Furthermore, we demonstrated that the LIM domains of zyxin are sufficient for DNA binding and that zyxin knockdown leads to transcriptional changes in mitochondrial pseudogenes. Additionally, zyxin knockdown impacted several other genes associated with mitochondrial integrity and apoptosis, resulting in disturbances in MTCO2P2 RNA localization, mitochondrial membrane potential, increased reactive oxygen species, alterations in the cell cycle, and progression towards apoptosis. Overall, our work shows that zyxin directly interacts with nuclear DNA and regulates the transcription of mitochondrial pseudogenes, emphasizing its role in modulating mitochondrial function.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-16"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658261","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}
引用次数: 0
Lysosomal enzyme processing and trafficking in the social amoeba Dictyostelium discoideum. 群居变形虫盘齿钢齿的溶酶体酶加工和运输。
IF 2.4 3区 生物学
Biochemistry and Cell Biology Pub Date : 2025-01-01 DOI: 10.1139/bcb-2025-0062
Sean V Condie, William D Kim, Robert J Huber
{"title":"Lysosomal enzyme processing and trafficking in the social amoeba <i>Dictyostelium discoideum</i>.","authors":"Sean V Condie, William D Kim, Robert J Huber","doi":"10.1139/bcb-2025-0062","DOIUrl":"10.1139/bcb-2025-0062","url":null,"abstract":"<p><p><i>Dictyostelium discoideum</i> is a single-celled protist that undergoes multicellular development in response to nutrient deprivation. For close to a century, <i>D. discoideum</i> has been used as a model system for studying conserved cellular and developmental processes such as chemotaxis, cell adhesion, and cell differentiation. In the later decades of the 20th century, intensive research efforts examined the synthesis, trafficking, and activity of lysosomal enzymes in <i>D. discoideum</i>. Subsequent work revealed that lysosomes are essential for all stages of the <i>D. discoideum</i> life cycle and the genome encodes dozens of homologs of human lysosomal enzymes, including those associated with lysosomal storage diseases. Additionally, protocols for examining the trafficking and activity of lysosomal enzymes in <i>D. discoideum</i> are well-established. Here, we provide a comprehensive up-to-date review that summarizes our current knowledge of lysosomal enzyme processing and trafficking in <i>D. discoideum</i>, with an eye towards re-establishing <i>D. discoideum</i> as a model eukaryote for studying the functions of conserved lysosomal enzymes and the pathways that regulate their trafficking.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-11"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762980","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}
引用次数: 0
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