Biochimica et Biophysica Acta-Gene Regulatory Mechanisms最新文献_第6页

DDX5 (p68) orchestrates β-catenin, RelA and SP1 mediated MGMT gene expression in human colon cancer cells: Implication in TMZ chemoresistance DDX5（p68）在人结肠癌癌症细胞中协调β-连环蛋白、RelA和SP1介导的MGMT基因表达：TMZ化疗耐药性的意义。

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-10-02 DOI: 10.1016/j.bbagrm.2023.194991

Rajni Shaw , Subhajit Karmakar , Malini Basu , Mrinal K. Ghosh

{"title":"DDX5 (p68) orchestrates β-catenin, RelA and SP1 mediated MGMT gene expression in human colon cancer cells: Implication in TMZ chemoresistance","authors":"Rajni Shaw , Subhajit Karmakar , Malini Basu , Mrinal K. Ghosh","doi":"10.1016/j.bbagrm.2023.194991","DOIUrl":"10.1016/j.bbagrm.2023.194991","url":null,"abstract":"<div>DDX5 (p68) upregulation has been linked with various cancers of different origins, especially Colon Adenocarcinomas. Similarly, across cancers, MGMT has been identified as the major contributor of chemoresistance against DNA alkylating agents like Temozolomide (TMZ). TMZ is an emerging potent chemotherapeutic agent across cancers under the arena of drug repurposing. Recent studies have established that patients with open MGMT promoters are prone to be innately resistant or acquire resistance against TMZ compared to its closed conformation. However, not much is known about the transcriptional regulation of MGMT gene in the context of colon cancer. This necessitates studying MGMT gene regulation which directly impacts the cellular potential to develop chemoresistance against alkylating agents. Our study aims to uncover an unidentified mechanism of DDX5-mediated MGMT gene regulation. Experimentally, we found that both mRNA and protein expression levels of MGMT were elevated in response to p68 overexpression in multiple human colon cancer cell lines and vice-versa. Since p68 cannot directly interact with the MGMT promoter, transcription factors viz., β-catenin, RelA (p65) and SP1 were also studied as reported contributors. Through co-immunoprecipitation and GST-pull-down studies, p68 was established as an interacting partner of SP1 in addition to β-catenin and NF-κB (p50-p65). Mechanistically, luciferase reporter and chromatin-immunoprecipitation assays demonstrated that p68 interacts with the MGMT promoter via TCF4-LEF, RelA and SP1 sites to enhance its transcription. To the best of our knowledge, this is the first report of p68 as a transcriptional co-activator of MGMT promoter and our study identifies p68 as a novel and master regulator of MGMT gene expression.</div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 4","pages":"Article 194991"},"PeriodicalIF":4.7,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41154520","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

Unraveling the battle for lysine: A review of the competition among post-translational modifications 揭开赖氨酸之战：翻译后修饰之间的竞争综述。

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-09-24 DOI: 10.1016/j.bbagrm.2023.194990

Ali H. Shukri , Valentina Lukinović , François Charih , Kyle K. Biggar

{"title":"Unraveling the battle for lysine: A review of the competition among post-translational modifications","authors":"Ali H. Shukri , Valentina Lukinović , François Charih , Kyle K. Biggar","doi":"10.1016/j.bbagrm.2023.194990","DOIUrl":"10.1016/j.bbagrm.2023.194990","url":null,"abstract":"<div>Proteins play a critical role as key regulators in various biological systems, influencing crucial processes such as gene expression, cell cycle progression, and cellular proliferation. However, the functions of proteins can be further modified through post-translational modifications (PTMs), which expand their roles and contribute to disease progression when dysregulated. In this review, we delve into the methodologies employed for the characterization of PTMs, shedding light on the techniques and tools utilized to help unravel their complexity. Furthermore, we explore the prevalence of crosstalk and competition that occurs between different types of PTMs, specifically focusing on both histone and non-histone proteins. The intricate interplay between different modifications adds an additional layer of regulation to protein function and cellular processes. To gain insights into the competition for lysine residues among various modifications, computational systems such as MethylSight have been developed, allowing for a comprehensive analysis of the modification landscape. Additionally, we provide an overview of the exciting developments in the field of inhibitors or drugs targeting PTMs, highlighting their potential in combatting prevalent diseases. The discovery and development of drugs that modulate PTMs present promising avenues for therapeutic interventions, offering new strategies to address complex diseases. As research progresses in this rapidly evolving field, we anticipate remarkable advancements in our understanding of PTMs and their roles in health and disease, ultimately paving the way for innovative treatment approaches.</div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 4","pages":"Article 194990"},"PeriodicalIF":4.7,"publicationDate":"2023-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41121904","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

Post-translational modifications in stress granule and their implications in neurodegenerative diseases 应激颗粒的翻译后修饰及其在神经退行性疾病中的意义。

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-09-24 DOI: 10.1016/j.bbagrm.2023.194989

Zhangshun Wang , Chen'ang Zhang , Chengyu Fan, Yanfen Liu

{"title":"Post-translational modifications in stress granule and their implications in neurodegenerative diseases","authors":"Zhangshun Wang , Chen'ang Zhang , Chengyu Fan, Yanfen Liu","doi":"10.1016/j.bbagrm.2023.194989","DOIUrl":"10.1016/j.bbagrm.2023.194989","url":null,"abstract":"<div>Stress granules (SGs) arise as formations of mRNAs and proteins in response to translation initiation inhibition during stress. These dynamic compartments adopt a fluidic nature through liquid-liquid phase separation (LLPS), exhibiting a composition subject to constant change within cellular contexts. Research has unveiled an array of post-translational modifications (PTMs) occurring on SG proteins, intricately orchestrating SG dynamics. In the realm of neurodegenerative diseases, pathological mutant proteins congregate into insoluble aggregates alongside numerous SG proteins, manifesting resilience against disassembly. Specific PTMs conspicuously label these aggregates, designating them for subsequent degradation. The strategic manipulation of aberrant SGs via PTMs emerges as a promising avenue for therapeutic intervention. This review discerns recent strides in comprehending the impact of PTMs on LLPS behavior and the assembly/disassembly kinetics of SGs. By delving into the roles of PTMs in governing SG dynamics, we augment our cognizance of the molecular underpinnings of neurodegeneration. Furthermore, we offer invaluable insights into potential targets for therapeutic intervention in neurodegenerative afflictions, encompassing conditions like amyotrophic lateral sclerosis and frontotemporal dementia.</div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 4","pages":"Article 194989"},"PeriodicalIF":4.7,"publicationDate":"2023-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41107119","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

Entanglement of MAPK pathways with gene expression and its omnipresence in the etiology for cancer and neurodegenerative disorders MAPK途径与基因表达的纠缠及其在癌症和神经退行性疾病病因中的普遍存在。

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-09-21 DOI: 10.1016/j.bbagrm.2023.194988

Joydeep Chakraborty , Sayan Chakraborty , Sohag Chakraborty , Mahesh N. Narayan

{"title":"Entanglement of MAPK pathways with gene expression and its omnipresence in the etiology for cancer and neurodegenerative disorders","authors":"Joydeep Chakraborty , Sayan Chakraborty , Sohag Chakraborty , Mahesh N. Narayan","doi":"10.1016/j.bbagrm.2023.194988","DOIUrl":"10.1016/j.bbagrm.2023.194988","url":null,"abstract":"<div>Mitogen Activated Protein Kinase (MAPK) is one of the most well characterized cellular signaling pathways that controls fundamental cellular processes including proliferation, differentiation, and apoptosis. These cellular functions are consequences of transcription of regulatory genes that are influenced and regulated by the MAP-Kinase signaling cascade. MAP kinase components such as Receptor Tyrosine Kinases (RTKs) sense external cues or ligands and transmit these signals via multiple protein complexes such as RAS–RAF, MEK, and ERKs and eventually modulate the transcription factors inside the nucleus to induce transcription and other regulatory functions. Aberrant activation, dysregulation of this signaling pathway, and genetic alterations in any of these components results in the developmental disorders, cancer, and neurodegenerative disorders. Over the years, the MAPK pathway has been a prime pharmacological target, to treat complex human disorders that are genetically linked such as cancer, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The current review re-visits the mechanism of MAPK pathways in gene expression regulation. Further, a current update on the progress of the mechanistic understanding of MAPK components is discussed from a disease perspective.</div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 4","pages":"Article 194988"},"PeriodicalIF":4.7,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41171037","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: 1

Inflammation-induced nitric oxide suppresses PPARα expression and function via downregulation of Sp1 transcriptional activity in adipocytes 炎症诱导的一氧化氮通过下调脂肪细胞中Sp1转录活性来抑制PPARα的表达和功能。

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-09-20 DOI: 10.1016/j.bbagrm.2023.194987

Jungin Kwon , Yumeko Aoki , Haruya Takahashi , Rieko Nakata , Satoko Kawarasaki , Zheng Ni , Rina Yu , Hiroyasu Inoue , Kazuo Inoue , Teruo Kawada , Tsuyoshi Goto

{"title":"Inflammation-induced nitric oxide suppresses PPARα expression and function via downregulation of Sp1 transcriptional activity in adipocytes","authors":"Jungin Kwon , Yumeko Aoki , Haruya Takahashi , Rieko Nakata , Satoko Kawarasaki , Zheng Ni , Rina Yu , Hiroyasu Inoue , Kazuo Inoue , Teruo Kawada , Tsuyoshi Goto","doi":"10.1016/j.bbagrm.2023.194987","DOIUrl":"10.1016/j.bbagrm.2023.194987","url":null,"abstract":"<div>The activation of peroxisome proliferator-activated receptor alpha (PPARα), a ligand-dependent transcription factor that regulates lipid oxidation-related genes, has been employed to treat hyperlipidemia. Emerging evidence indicates that Ppara gene expression decreases in adipose tissue under obese conditions; however, the underlying molecular mechanisms remain elusive. Here, we demonstrate that nitric oxide (NO) suppresses Ppara expression by regulating its promoter activity via suppression of specificity protein 1 (Sp1) transcriptional activity in adipocytes. NO derived from lipopolysaccharide (LPS) -activated macrophages or a NO donor (NOR5) treatment, suppressed Ppara mRNA expression in 10T1/2 adipocytes. In addition, Ppara transcript levels were reduced in the white adipose tissue (WAT) in both acute and chronic inflammation mouse models; however, such suppressive effects were attenuated via a nitric oxide synthase 2 (NOS2) inhibitor. Endoplasmic reticulum (ER) stress inhibitors attenuated the NO-induced repressive effects on Ppara gene expression in 10T1/2 adipocytes. Promoter mutagenesis and chromatin immunoprecipitation assays revealed that NO decreased the Sp1 occupancy in the proximal promoter regions of the Ppara gene, which might partially result from the reduced Sp1 expression levels by NO. This study delineated the molecular mechanism that modulates Ppara gene transcription upon NO stimulation in white adipocytes, suggesting a possible mechanism for the transcriptional downregulation of Ppara in WAT under obese conditions.</div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 4","pages":"Article 194987"},"PeriodicalIF":4.7,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41152923","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

Post translational modifications at the verge of plant-geminivirus interaction 植物双子病毒相互作用边缘的翻译后修饰。

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-09-17 DOI: 10.1016/j.bbagrm.2023.194983

Ashish Prasad , Shambhavi Sharma , Manoj Prasad

{"title":"Post translational modifications at the verge of plant-geminivirus interaction","authors":"Ashish Prasad , Shambhavi Sharma , Manoj Prasad","doi":"10.1016/j.bbagrm.2023.194983","DOIUrl":"10.1016/j.bbagrm.2023.194983","url":null,"abstract":"<div>Plant-virus interaction is a complex phenomenon and involves the communication between plant and viral factors. Viruses have very limited coding ability yet, they are able to cause infection which results in huge agro-economic losses throughout the globe each year. Post-translational modifications (PTMs) are covalent modifications of proteins that have a drastic effect on their conformation, stability and function. Like the host proteins, geminiviral proteins are also subject to PTMs and these modifications greatly expand the diversity of their functions. Additionally, these viral proteins can also interact with the components of PTM pathways and modulate them. Several studies have highlighted the importance of PTMs such as phosphorylation, ubiquitination, SUMOylation, myristoylation, S-acylation, acetylation and methylation in plant-geminivirus interaction. PTMs also regulate epigenetic modifications during geminivirus infection which determines viral gene expression. In this review, we have summarized the role of PTMs in regulating geminiviral protein function, influence of PTMs on viral gene expression and how geminiviral proteins interact with the components of PTM pathways to modulate their function.</div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 4","pages":"Article 194983"},"PeriodicalIF":4.7,"publicationDate":"2023-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10651925","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

Regulation of SARS-CoV-2 infection and antiviral innate immunity by ubiquitination and ubiquitin-like conjugation 通过泛素化和泛素样结合调节严重急性呼吸系统综合征冠状病毒2型感染和抗病毒先天免疫。

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-09-17 DOI: 10.1016/j.bbagrm.2023.194984

Yi Zheng , Huiyu Yang , Xuejing Zhang , Chengjiang Gao

{"title":"Regulation of SARS-CoV-2 infection and antiviral innate immunity by ubiquitination and ubiquitin-like conjugation","authors":"Yi Zheng , Huiyu Yang , Xuejing Zhang , Chengjiang Gao","doi":"10.1016/j.bbagrm.2023.194984","DOIUrl":"10.1016/j.bbagrm.2023.194984","url":null,"abstract":"<div>A global pandemic COVID-19 resulting from SARS-CoV-2 has affected a significant portion of the human population. Antiviral innate immunity is critical for controlling and eliminating the viral infection. Ubiquitination is extensively involved in antiviral signaling, and recent studies suggest that ubiquitin-like proteins (Ubls) modifications also participate in innate antiviral pathways such as RLR and cGAS-STING pathways. Notably, virus infection harnesses ubiquitination and Ubls modifications to facilitate viral replication and counteract innate antiviral immunity. These observations indicate that ubiquitination and Ubls modifications are critical checkpoints for the tug-of-war between virus and host. This review discusses the current progress regarding the modulation of the SARS-CoV-2 life cycle and antiviral innate immune pathways by ubiquitination and Ubls modifications. This paper emphasizes the arising concept that ubiquitination and Ubls modifications are powerful modulators of virus and host interaction and potential drug targets for treating the infection of SARS-CoV-2.</div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 4","pages":"Article 194984"},"PeriodicalIF":4.7,"publicationDate":"2023-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10339041","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 mechanism of UP1 binding and unfolding of human telomeric DNA G-quadruplex 人端粒DNA G-四链体UP1结合和去折叠的机制。

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-09-16 DOI: 10.1016/j.bbagrm.2023.194985

Xiaobin Ling , Yuqi Yao , Lei Ding , Jinbiao Ma

{"title":"The mechanism of UP1 binding and unfolding of human telomeric DNA G-quadruplex","authors":"Xiaobin Ling , Yuqi Yao , Lei Ding , Jinbiao Ma","doi":"10.1016/j.bbagrm.2023.194985","DOIUrl":"10.1016/j.bbagrm.2023.194985","url":null,"abstract":"<div>The human telomere contains multiple copies of the DNA sequence d(TTAGGG) which can fold into higher order intramolecular G-quadruplexes and regulate the maintenance of telomere length and chromosomal integrity. The nucleic acid binding protein heteronuclear ribonucleoprotein A1 (hnRNP A1) and its N-terminus proteolytic product UP1 have been shown to efficiently bind and unfold telomeric DNA G-quadruplex. However, the understanding of the molecular mechanism of the UP1 binding and unfolding telomeric G-quadruplexes is still limited. Here, we performed biochemical and biophysical characterizations of UP1 binding and unfolding of human telomeric DNA G-quadruplex d[AGGG(TTAGGG)3], and in combination of systematic site-direct mutagenesis of two tandem RNA recognition motifs (RRMs) in UP1, revealed that RRM1 is responsible for initial binding and unfolding, whereas RRM2 assists RRM1 to complete the unfolding of G-quadruplex. Isothermal titration calorimetry (ITC) and circular dichroism (CD) studies of the interactions between UP1 and DNA G-quadruplex variants indicate that the “TAG” binding motif in Loop2 of telomeric G-quadruplex is critical for UP1 recognition and G-quadruplex unfolding initiation. Together we depict a model for molecular mechanism of hnRNP A1 (UP1) binding and unfolding of the human telomeric DNA G-quadruplex.</div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 4","pages":"Article 194985"},"PeriodicalIF":4.7,"publicationDate":"2023-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10634108","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

KDM5A noncanonically binds antagonists MLL1/2 to mediate gene regulation and promotes epithelial to mesenchymal transition KDM5A与拮抗剂MLL1/2非经典结合以介导基因调节并促进上皮向间充质的转变。

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-09-16 DOI: 10.1016/j.bbagrm.2023.194986

R. Kirtana, Soumen Manna, Samir Kumar Patra

{"title":"KDM5A noncanonically binds antagonists MLL1/2 to mediate gene regulation and promotes epithelial to mesenchymal transition","authors":"R. Kirtana, Soumen Manna, Samir Kumar Patra","doi":"10.1016/j.bbagrm.2023.194986","DOIUrl":"10.1016/j.bbagrm.2023.194986","url":null,"abstract":"<div>Differential expression of genes involved in certain processes is a collaborative outcome of crosstalk between signalling molecules and epigenetic modifiers. In response to environmental stimulus, interplay between transcription factors and epigenetic modifiers together dictates the regulation of genes. MLLs and KDM5A are functionally antagonistic proteins, as one acts as a writer and the other erases the active chromatin mark, i.e., H3K4me3. KDM5A influences the process of EMT by binding to both epithelial and mesenchymal gene promoters. Through this work, we show that when bound to E-cadherin promoter, KDM5A acts as a classical repressor by demethylating H3K4me3, but on mesenchymal markers, it acts as a transcriptional activator by inhibiting the activity of HDACs and increasing H3K18ac. Further, through our chromatin immunoprecipitation experiments, we observed a co-occupancy of KDM5A with MLLs, we tested whether KDM5A might physically interact with MLLs and WDR5, and here we provide experimental evidence that KDM5A indeed interacts with MLLs and WDR5.</div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 4","pages":"Article 194986"},"PeriodicalIF":4.7,"publicationDate":"2023-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10673517","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: 1

PP2A and its adapter protein IER5 induce the DNA-binding ability and target gene expression of E2F1 via dephosphorylation at serine 375 PP2A及其适配蛋白IER5通过丝氨酸375的去磷酸化诱导E2F1的dna结合能力和靶基因表达

IF 4.7 3区生物学

Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-09-01 DOI: 10.1016/j.bbagrm.2023.194960

Hiroto Takeuchi, Mayuko Koga, Kuriko Doi, Hiroshi Sakurai

{"title":"PP2A and its adapter protein IER5 induce the DNA-binding ability and target gene expression of E2F1 via dephosphorylation at serine 375","authors":"Hiroto Takeuchi, Mayuko Koga, Kuriko Doi, Hiroshi Sakurai","doi":"10.1016/j.bbagrm.2023.194960","DOIUrl":"10.1016/j.bbagrm.2023.194960","url":null,"abstract":"<div>The transcription factor E2F1 participates in cell cycle control through transcriptional activation of genes that promote S-phase entry. E2F1 is also linked to the expression of proapoptotic genes, and the loss of E2F1 activity facilitates tumor progression by reducing cellular apoptosis. Phosphorylation controlled by protein kinases and phosphatases is the major posttranslational modification and regulates the cellular levels and transactivator function of E2F1. Here, we characterize the regulatory roles of serine-375 (S375), one of the major phosphorylation sites of E2F1. Cyclin-dependent kinases such as CDK8 phosphorylate at S375 of E2F1, which is dephosphorylated by protein phosphatase 2A (PP2A) containing the B55 regulatory subunit. The PP2A adapter protein IER5 binds to both PP2A/B55 and E2F1 and assists dephosphorylation at S375 by PP2A. S375-dephosphorylated E2F1 exhibits higher DNA-binding affinity than the phosphorylated form. Although the promoter regions of proapoptotic genes are less occupied by E2F1 in cells, an increase in S375-dephosphorylated E2F1 induces preferential binding of E2F1 to the proapoptotic gene promoters and their expression. Our data identify PP2A/B55-IER5 as a critical regulator of E2F1 and suggest that the phosphorylation state of E2F1 is an important determinant for the expression of proapoptotic genes.</div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 3","pages":"Article 194960"},"PeriodicalIF":4.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10035062","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