Biochimica et Biophysica Acta-Gene Regulatory Mechanisms最新文献

The cAMP receptor protein, SyCRP1 acts as a transcriptional repressor of CO2-concentrating mechanism genes at high inorganic carbon levels in Synechocystis PCC 6803 聚囊藻（Synechocystis PCC 6803）中，cAMP受体蛋白SyCRP1作为高无机碳水平下co2富集机制基因的转录抑制因子。

IF 3.1 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2025-10-02 DOI: 10.1016/j.bbagrm.2025.195117

Suraj Chauhan , N. Prakash Prabhu , Martin Hagemann , Sue Lin-Chao , Jogadhenu S.S. Prakash

{"title":"The cAMP receptor protein, SyCRP1 acts as a transcriptional repressor of CO2-concentrating mechanism genes at high inorganic carbon levels in Synechocystis PCC 6803","authors":"Suraj Chauhan , N. Prakash Prabhu , Martin Hagemann , Sue Lin-Chao , Jogadhenu S.S. Prakash","doi":"10.1016/j.bbagrm.2025.195117","DOIUrl":"10.1016/j.bbagrm.2025.195117","url":null,"abstract":"<div><div>Cyanobacteria utilize a CO<sub>2</sub>-concentrating mechanism (CCM) to enhance photosynthetic efficiency by accumulating CO<sub>2</sub> around RuBisCO, a process crucial for adapting to fluctuating environmental CO<sub>2</sub> levels. While the upregulation of CCM genes under low inorganic carbon (C<sub>i</sub>) conditions is known, the precise C<sub>i</sub> sensing and regulatory mechanisms governing CCM gene expression remain incompletely understood. We show that a membrane-bound SyCRP1 senses high C<sub>i</sub> levels through cAMP binding to its low- and high-affinity sites. We demonstrate its interaction with membrane lipids and liposomes, and a subsequent reversal of its membrane localization upon cAMP binding. Comprehensive ChIP-seq analysis reveals direct binding of SyCRP1 to regulatory elements of core CCM genes. Our findings establish SyCRP1 as a key transcriptional repressor of these genes under high C<sub>i</sub> conditions, significantly advancing our understanding of the molecular mechanisms governing CCM genes' expression in cyanobacteria.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1868 4","pages":"Article 195117"},"PeriodicalIF":3.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226313","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

Transcriptional activation of the PKLR gene by novel erythroid-specific regulatory elements 新的红细胞特异性调控元件对plklr基因转录激活的影响。

IF 3.1 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2025-09-16 DOI: 10.1016/j.bbagrm.2025.195116

Yea Woon Kim , Jin Kang , AeRi Kim

{"title":"Transcriptional activation of the PKLR gene by novel erythroid-specific regulatory elements","authors":"Yea Woon Kim , Jin Kang , AeRi Kim","doi":"10.1016/j.bbagrm.2025.195116","DOIUrl":"10.1016/j.bbagrm.2025.195116","url":null,"abstract":"<div><div>The pyruvate kinase L/R (PKLR) gene encodes the L- and R-type isoforms of pyruvate kinase, which catalyze the final step of glycolysis in mammals. The L-type isozyme is mainly found in liver cells, whereas the R-type isozyme is produced specifically in erythroid cells. To investigate the transcriptional activation of the PKLR gene for the R-type isozyme, we analyzed chromatin features—including DNase I sensitivity, histone modifications, and enhancer–promoter interactions—in erythroid K562 and non-erythroid HUVEC cells. Putative regulatory elements, including a promoter and two enhancers, were identified near the PKLR locus in K562 cells. Depletion of H3K4me1 and H3K27ac, histone marks associated with active enhancers, through mutation of histone methyltransferases led to a marked reduction in PKLR transcription, while transcription of a nearby gene remained stable. These regulatory elements were highly occupied by the erythroid-specific transcription factors GATA1 and TAL1. Loss of either factors disrupted local H3K27ac and reduced the recruitment of chromatin-looping factors, resulting in decreased PKLR transcription. Furthermore, CRISPR/Cas9-mediated deletion of the putative regulatory elements significantly diminished PKLR transcription, demonstrating their functional importance. Collectively, these findings highlight the essential role of these regulatory elements in activating PKLR transcription in erythroid cells and emphasize the requirement of erythroid-specific factors for their function.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1868 4","pages":"Article 195116"},"PeriodicalIF":3.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087956","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

RNA-protein interaction techniques - A historical and comparative analysis rna -蛋白质相互作用技术-历史和比较分析。

IF 3.1 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2025-09-11 DOI: 10.1016/j.bbagrm.2025.195115

Sourabh Chakrabarty , Sayan Roy , Soumyadip Sarkar , Kusum K. Singh

{"title":"RNA-protein interaction techniques - A historical and comparative analysis","authors":"Sourabh Chakrabarty , Sayan Roy , Soumyadip Sarkar , Kusum K. Singh","doi":"10.1016/j.bbagrm.2025.195115","DOIUrl":"10.1016/j.bbagrm.2025.195115","url":null,"abstract":"<div><div>RNAs intricately orchestrate a myriad of molecular and cellular processes. This includes mRNAs which serve as the essential blueprints for protein synthesis and the non-coding RNAs which act as versatile regulators, influencing gene expression, RNA stability, and even protein function. Over the past few decades, a diverse array of RNA- and protein-centric methodologies have emerged to discern and elucidate the identities of RNA binding proteins (RBPs) and RNAs engaged in RNA-Protein interactions (RPI). The selection of an appropriate method is paramount, given the distinctive advantages and limitations inherent to each technique, in order to effectively address specific biological inquiries. This review spans the spectrum of techniques employed in RNA-Protein interaction studies, ranging from time-honored methods like Electrophoretic Mobility Shift Assay (EMSA) to contemporary approaches such as CRISPR-based RNA-Protein interaction profiling (CBRIP). This review aims not only to list methods but also to provide historical background, discuss the strengths and weaknesses of each approach, and highlight their current applications. Furthermore, it consolidates methodologies tailored to characterize RNA-protein interactions based on their distinct purposes.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1868 4","pages":"Article 195115"},"PeriodicalIF":3.1,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058811","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

The Catsper3 promoter activity is regulated by the cAMP-Response Element Modulator tau (CREMτ) and the cAMP-Response Element Binding protein 1A (CREBA) transcription factors Catsper3启动子活性受cAMP-Response Element Modulator tau （CREMτ）和cAMP-Response Element Binding protein 1A （CREBA）转录因子调控

IF 3.1 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2025-08-25 DOI: 10.1016/j.bbagrm.2025.195114

Diego Eduardo Sánchez-Jasso , Sergio Federico López-Guzmán , Javier Hernández-Sánchez , Rosa María Bermúdez-Cruz , Norma Oviedo

{"title":"The Catsper3 promoter activity is regulated by the cAMP-Response Element Modulator tau (CREMτ) and the cAMP-Response Element Binding protein 1A (CREBA) transcription factors","authors":"Diego Eduardo Sánchez-Jasso , Sergio Federico López-Guzmán , Javier Hernández-Sánchez , Rosa María Bermúdez-Cruz , Norma Oviedo","doi":"10.1016/j.bbagrm.2025.195114","DOIUrl":"10.1016/j.bbagrm.2025.195114","url":null,"abstract":"<div><div>Catsper3 has been shown to be essential for the proper functioning of CatSper calcium channel, sperm hyperactivation and egg fertilization. Although its function and physiological relevance to male fertility have been characterized, nothing is known about its regulation at the transcriptional level. Here, we identified the murine <em>Catsper3</em> promoter and evaluated the role of CREBA and CREMτ transcription factors (TF) on its regulation. Cloning of a predicted <em>Catsper3</em> promoter region and further deletion analysis indicates that <em>Catsper3</em> core promoter is located at −157 to +152 relative to the transcription start site (TSS). Mutation of a TATA box and a Downstream Promoter Element (DPE) did not alter the promoter activity, indicating that this promoter is TATA and DPE independent. Exogenous expression of CREBA and CREMτ increase the <em>Catsper3</em> promoter activity in the presence of the +268 to +439 region, where two CRE sites were predicted, and mutation of both CRE sites prevents the transactivation by both TFs, suggesting that CREMτ and CREBA may use these sites to promote <em>Catsper3</em> transcription. Finally, binding of CREBA and CREMτ to both CRE sites was confirmed <em>in vitro</em> by EMSA and ChIP-qPCR assays demonstrated an enrichment of CREBA and CREMτ at the <em>Catsper3</em> promoter <em>in vivo</em> in the testis but not in liver, indicating its tissue-specific binding. Altogether, these results strongly suggest that <em>Catsper3</em> gene has a TATA-less, DPE independent promoter encompassed by −157 to +152 region around TSS and that <em>Catsper3</em> gene expression is directly regulated through two CRE sites by CREBA and CREMτ.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1868 4","pages":"Article 195114"},"PeriodicalIF":3.1,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919682","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

Expression of CMK2 is controlled by the general stress-response transcriptional factor Msn2 through a single STRE site in budding yeast 在出芽酵母中，CMK2的表达受一般应激反应转录因子Msn2通过一个单一的STRE位点控制。

IF 3.1 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2025-08-13 DOI: 10.1016/j.bbagrm.2025.195107

Linghuo Jiang , Yiying Gu , Liudan Wei , Jinrong Feng , Lingxin Pan , Xiufan Liao , Yiping Mo , Chunyu Wei

{"title":"Expression of CMK2 is controlled by the general stress-response transcriptional factor Msn2 through a single STRE site in budding yeast","authors":"Linghuo Jiang , Yiying Gu , Liudan Wei , Jinrong Feng , Lingxin Pan , Xiufan Liao , Yiping Mo , Chunyu Wei","doi":"10.1016/j.bbagrm.2025.195107","DOIUrl":"10.1016/j.bbagrm.2025.195107","url":null,"abstract":"<div><div>Mammalian calcium/calmodulin-dependent protein kinase II (CaMKII) is a memory molecule in the brain, and regulates fatty acids and lipid metabolism. As a yeast homolog of CaMKII, Cmk2 is a negative feed-back regulator of calcium signaling in <em>Saccharomyces cerevisiae</em>. Previous systemic studies have shown that 42 transcription factors (TFs) are involved in the control of <em>CMK2</em> expression under various conditions other than calcium stress, but only one, Crz1, is reported to directly regulate <em>CMK2</em> expression in response to calcium stress. Here, we show that other 26 TFs, Adr1, Aft2, Cad1, Cst6, Cup2, Dal81, Dal82, Flo8, Gcr2, Haa1, Hfi1, Msn2, Oaf1, Pho4, Ppr1, Rfx1, Rgm1, Rpn4, Sfp1, SIp3, Smp1, Spt10, Stp1, Sum1, Swi4 and Tup1, are involved in the positive control of <em>CMK2</em> transcription, with 10 of them being calcium stress-specific. In contrast, other four TFs, Hir2, Rph1, Sin3 and Uga3, negatively regulates <em>CMK2</em> transcription independent of calcium stress. Therefore, multiple TFs directly or indirectly control the transcription of <em>CMK2</em> in yeast cells. EMSA and ChIP analysis demonstrate that the general stress-responsive Msn2 directly controls the expression of <em>CMK2</em> through one STRE site, 5′ C<sub>−155</sub>CCCT 3′, in its promoter. Our genetic study indicates that Crz1 is epistatic to Msn2 in controlling <em>CMK2</em> expression and the calcium sensitivity of yeast cells in response to calcium stress. This work provides important clues to the study on the regulation of CaMKII expression in mammalian cells.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1868 4","pages":"Article 195107"},"PeriodicalIF":3.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859964","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

A putative PIWIL/piRNA–OTX2 network: An emerging model for epigenetic regulation of cancer stemness in retinoblastoma PIWIL/piRNA-OTX2网络：视网膜母细胞瘤肿瘤干细胞的表观遗传调控新模型

IF 2.6 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2025-07-19 DOI: 10.1016/j.bbagrm.2025.195106

Rupa Roy , Subbulakshmi Chidambaram

{"title":"A putative PIWIL/piRNA–OTX2 network: An emerging model for epigenetic regulation of cancer stemness in retinoblastoma","authors":"Rupa Roy , Subbulakshmi Chidambaram","doi":"10.1016/j.bbagrm.2025.195106","DOIUrl":"10.1016/j.bbagrm.2025.195106","url":null,"abstract":"<div><div>Recent findings underscore the critical role of PIWIL/piRNA pathways in cancer, extending their known functions beyond reproductive biology. Retinoblastoma (RB), a rare pediatric retinal tumor, is primarily driven by RB1 gene loss but also involves significant epigenetic alterations. Our previous studies revealed that PIWIL4 is significantly upregulated in RB, and its knockdown disrupts the expression of stemness-associated factors, including OTX2, SOX2, and NANOG. In this review, we have proposed that PIWIL/piRNA complexes might recruit epigenetic modifiers to cis-regulatory modules (CRMs) of the OTX2 gene, modulating chromatin accessibility and transcription factor binding. Aberrant PIWIL4 expression may dysregulate OTX2 expression, impacting stemness-maintaining factors and activating oncogenic pathways, including Wnt/β-catenin signaling, mediated by TSPAN12, EphA2, and ZNF proteins. This conceptual framework positions the PIWIL/piRNA-OTX2 axis as a potential regulator of CSC dynamics, linking it to epigenetic modifications, transcription factor interactions, and neuronal differentiation in RB. Targeting this axis could disrupt stemness-associated pathways and oncogenic signaling, offering new therapeutic strategies to mitigate tumor progression and recurrence in RB and other cancers with similar molecular mechanisms.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1868 3","pages":"Article 195106"},"PeriodicalIF":2.6,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144683636","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

Functional characterization of promoter regions in selenoprotein synthesis-relevant genes (sbp2, eefsec and sepsecs) and their selenium-dependent regulation in yellow catfish Pelteobagrus fulvidraco 黄颡鱼硒蛋白合成相关基因（sbp2、eefsec和sepsecs）启动子区功能特征及其硒依赖性调控

IF 2.6 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2025-07-04 DOI: 10.1016/j.bbagrm.2025.195105

Kai Zhang , An-Gen Yu , Hua Zheng , Pei-Jia Li , Zhi Luo

{"title":"Functional characterization of promoter regions in selenoprotein synthesis-relevant genes (sbp2, eefsec and sepsecs) and their selenium-dependent regulation in yellow catfish Pelteobagrus fulvidraco","authors":"Kai Zhang , An-Gen Yu , Hua Zheng , Pei-Jia Li , Zhi Luo","doi":"10.1016/j.bbagrm.2025.195105","DOIUrl":"10.1016/j.bbagrm.2025.195105","url":null,"abstract":"<div><div>The study explored the transcriptional regulation of selenoprotein synthesis-relevant genes, such as selenocysteine insertion sequence element binding protein 2 (<em>sbp2</em>), eukaryotic elongation factor (<em>eefsec</em>) and o-phosphoserine selenocysteine tRNA synthase (<em>sepsecs</em>), and their selenium-mediated regulation in yellow catfish <em>Pelteobagrus fulvidraco</em>, an important fish with ecological and economic importance in several Asian countries. We cloned the sequences of <em>sbp2</em>, <em>eefsec</em> and <em>sepsecs</em> promoters, spanning from −2060 bp to +61 bp, −1910 bp to +53 bp and − 1456 bp to +51 bp relative to the TSS, respectively. Through sequential deletion and mutation analysis of their promoters, we identified several functional binding sites: the signal transducer and activator of transcription 1 (STAT1) binding site (−1308 bp to −1322 bp) and the forkhead box protein O1 (FOXO1) binding site (−1778 bp to −1788 bp) in the <em>sbp2</em> promoter; the FOXO1 binding site (−1070 bp to −1080 bp) and the STAT3 binding site (−428 bp to −436 bp) in the <em>eefsec</em> promoter; and the FOXO1 binding site (−721 bp to −731 bp) in the <em>sepsecs</em> promoter. The activity of these binding sites was regulated by selenomethionine (Se-Met) incubation. Furthermore, electrophoretic mobility shift assay and chromatin immunoprecipitation experiments confirmed that these binding sites interact with their corresponding transcription factors above. For the first time, we demonstrated that STAT1 and FOXO1 regulate transcriptional activity of <em>sbp2</em> promoter; STAT3 and FOXO1 regulate transcriptional activity of <em>eefsec</em> promoter; and FOXO1 regulates transcriptional activity of <em>sepsecs</em> promoter. These findings provide novel insights into regulatory mechanisms of selenoprotein synthesis in yellow catfish.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1868 3","pages":"Article 195105"},"PeriodicalIF":2.6,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576996","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

Transposon insertion causes ctnnb2 transcript instability that results in the maternal effect zebrafish ichabod (ich) mutation 转座子插入导致ctnnb2转录不稳定，导致母体效应斑马鱼ichabod （rich）突变。

IF 2.6 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2025-06-30 DOI: 10.1016/j.bbagrm.2025.195104

Zsombor Varga , Ferenc Kagan , Shingo Maegawa , Ágnes Nagy , Javan Okendo , Shawn M. Burgess , Eric S. Weinberg , Máté Varga

{"title":"Transposon insertion causes ctnnb2 transcript instability that results in the maternal effect zebrafish ichabod (ich) mutation","authors":"Zsombor Varga , Ferenc Kagan , Shingo Maegawa , Ágnes Nagy , Javan Okendo , Shawn M. Burgess , Eric S. Weinberg , Máté Varga","doi":"10.1016/j.bbagrm.2025.195104","DOIUrl":"10.1016/j.bbagrm.2025.195104","url":null,"abstract":"<div><div>The maternal-effect mutation <em>ichabod</em> (<em>ich</em>) results in ventralized zebrafish embryos due to impaired induction of the dorsal canonical Wnt-signaling pathway. While previous studies linked the phenotype to reduced <em>ctnnb2</em> transcript levels, the causative mutation remained unidentified. Using long-read sequencing, we discovered that the <em>ich</em> phenotype stems from the insertion of a non-autonomous CMC-Enhancer/Suppressor-mutator (CMC-EnSpm) transposon in the 3’UTR of the gene. Through reporter assays, we demonstrate that while wild type <em>ctnnb2</em> mRNAs exhibit remarkably high stability throughout the early stages of development, the insertion of the transposon dramatically reduces transcript stability. Genome-wide mapping of the CMC-EnSpm transposons across multiple zebrafish strains also indicated ongoing transposition activity in the zebrafish genome. Our findings not only resolve the molecular basis of the <em>ich</em> mutation but also highlight the continuing mutagenic potential of endogenous transposons and reveal unexpected aspects of maternal transcript regulation during early zebrafish development.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1868 3","pages":"Article 195104"},"PeriodicalIF":2.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546267","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

DUSP1 protein's impact on breast cancer: Anticancer response and sensitivity to cisplatin DUSP1蛋白对乳腺癌的影响：抗癌反应和对顺铂的敏感性

IF 2.6 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2025-06-25 DOI: 10.1016/j.bbagrm.2025.195103

Sefa Metin , Hilal Altan , Ergün Tercan , Bala Gur Dedeoglu , Hakan Gurdal

{"title":"DUSP1 protein's impact on breast cancer: Anticancer response and sensitivity to cisplatin","authors":"Sefa Metin , Hilal Altan , Ergün Tercan , Bala Gur Dedeoglu , Hakan Gurdal","doi":"10.1016/j.bbagrm.2025.195103","DOIUrl":"10.1016/j.bbagrm.2025.195103","url":null,"abstract":"<div><div>Dual-Specificity Phosphatase 1 (DUSP1) modulates the activity of members of the Mitogen-Activated Protein Kinase (MAPK) family, including p38, JNK, and ERK1/2, which affects various cellular functions in cancer. Moreover, DUSP1 is known to influence the outcomes of cancer chemotherapy. This study aimed to reduce DUSP1 protein expression using CRISPR/Cas9 and siRNA and assess its effects on cell proliferation, migration, and tumor growth potential in triple-negative breast cancer (TNBC) cells. We examined the expression levels of p38, JNK, and ERK1/2, along with their phosphorylated forms, and investigated DUSP1's influence to cisplatin sensitivity<strong><em>.</em></strong> Our findings revealed that the downregulation of DUSP1 expression inhibited the proliferation, migration, and tumor growth potential of TNBC cells. Additionally, BCI, an inhibitor of DUSP1/6, demonstrated anti-proliferative effects on these cells. Decreasing the expression of DUSP1 increased the phosphorylation ratio of p38 and JNK, but not ERK1/2. Moreover, the anticancer response induced by cisplatin was enhanced by reducing DUSP1 expression or by treating the cells with BCI. Notably, cisplatin treatment increased p38 phosphorylation, which was significantly augmented by reduced DUSP1 expression. We also demonstrated that the DUSP1 inhibition-induced anticancer response in these cells predominantly relied on p38 activity. These findings contribute to a better understanding of the role of DUSP1 in breast cancer and offer insights into potential therapeutic strategies targeting DUSP1 to enhance the efficacy of cisplatin treatment. Our study highlights that decreased DUSP1 protein expression and activity mediates an anticancer response and increases the sensitivity of MDA-MB231 cells to cisplatin by regulating p38.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1868 3","pages":"Article 195103"},"PeriodicalIF":2.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482397","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

RhoA functionally collaborates with HSPA1A to promote the migratory phenotype of cancer cells RhoA与HSPA1A在功能上协同促进癌细胞的迁移表型

IF 2.6 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2025-06-20 DOI: 10.1016/j.bbagrm.2025.195101

Sumaiya Nabi , Mohammad Amin Hajam , Umar Mushtaq , Aadil Manzoor Baba , Bashir Ahmad Malla , Firdous Ahmad Khanday , Nazir Ahmad Dar

{"title":"RhoA functionally collaborates with HSPA1A to promote the migratory phenotype of cancer cells","authors":"Sumaiya Nabi , Mohammad Amin Hajam , Umar Mushtaq , Aadil Manzoor Baba , Bashir Ahmad Malla , Firdous Ahmad Khanday , Nazir Ahmad Dar","doi":"10.1016/j.bbagrm.2025.195101","DOIUrl":"10.1016/j.bbagrm.2025.195101","url":null,"abstract":"<div><div>RhoA, a member of the GTPase family, plays a pivotal role in attaining a migratory phenotype, mainly by regulating cytoskeleton dynamics, cell adhesion and membrane protrusions. Although many upstream regulators and downstream effectors of RhoA have been identified, the discovery of new interacting partners continues to expand its interactome, providing fresh insights into its regulation and function. Co-immunoprecipitation and fluorescence microscopy were used to study the interaction, localization and morphological effects of HSPA1A and RhoA. The interaction was validated by modulating the protein expression through transfections and silencing approaches. Cell proliferation, migration and viability were assessed using MTT, a Boyden chamber and FACS assays, respectively. Our study identified HSPA1A, as an unexplored interacting partner of RhoA under physiological conditions. Functional analyses showed that the interaction between HSPA1A and RhoA enhances the migratory potential of cancer cells, induces G0/G1 cell cycle arrest and promotes a rounded cell morphology. Under HSPA1A transfection, increased RhoA protein levels were observed, while the silencing of HSPA1A resulted in decreased RhoA levels. This study highlights the critical role of HSPA1A-RhoA interaction in regulating cancer cell migration, morphology and cell cycle progression. These findings lay the groundwork for future research into its potential clinical applications.</div></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1868 3","pages":"Article 195101"},"PeriodicalIF":2.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366089","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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