Biochimica et Biophysica Acta-Gene Regulatory Mechanisms最新文献

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Insight into the mechanism of AML del(9q) progression: hnRNP K targets the myeloid master regulators CEBPA (C/EBPα) and SPI1 (PU.1) AML del(9q)进展机制研究:hnRNP K靶向髓系主调控因子CEBPA (C/EBPα)和SPI1 (PU.1)。
IF 4.7 3区 生物学
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-11-25 DOI: 10.1016/j.bbagrm.2023.195004
Kerstin Rahn , Ali T. Abdallah , Lin Gan , Shelley Herbrich , Roland Sonntag , Oscar Benitez , Prerna Malaney , Xiaorui Zhang , Ashely G. Rodriguez , Jared Brottem , Gernot Marx , Tim H. Brümmendorf , Dirk H. Ostareck , Antje Ostareck-Lederer , Martina Crysandt , Sean M. Post , Isabel S. Naarmann-de Vries
{"title":"Insight into the mechanism of AML del(9q) progression: hnRNP K targets the myeloid master regulators CEBPA (C/EBPα) and SPI1 (PU.1)","authors":"Kerstin Rahn ,&nbsp;Ali T. Abdallah ,&nbsp;Lin Gan ,&nbsp;Shelley Herbrich ,&nbsp;Roland Sonntag ,&nbsp;Oscar Benitez ,&nbsp;Prerna Malaney ,&nbsp;Xiaorui Zhang ,&nbsp;Ashely G. Rodriguez ,&nbsp;Jared Brottem ,&nbsp;Gernot Marx ,&nbsp;Tim H. Brümmendorf ,&nbsp;Dirk H. Ostareck ,&nbsp;Antje Ostareck-Lederer ,&nbsp;Martina Crysandt ,&nbsp;Sean M. Post ,&nbsp;Isabel S. Naarmann-de Vries","doi":"10.1016/j.bbagrm.2023.195004","DOIUrl":"10.1016/j.bbagrm.2023.195004","url":null,"abstract":"<div><p><span>Deletions on the long arm of chromosome 9 (del(9q)) are recurrent abnormalities in about 2 % of acute myeloid leukemia cases, which usually involve </span><em>HNRNPK</em> and are frequently associated with other known aberrations. Based on an <em>Hnrnpk</em> haploinsufficient mouse model, a recent study demonstrated a function of hnRNP K in pathogenesis of myeloid malignancies <em>via</em><span><span> the regulation of cellular proliferation<span> and myeloid differentiation programs. Here, we provide evidence that reduced hnRNP K expression results in the dysregulated expression of C/EBPα and additional transcription factors. CyTOF analysis revealed monocytic skewing with increased levels of mature myeloid cells. To explore the role of hnRNP K during normal and pathological myeloid differentiation in humans, we characterized hnRNP K-interacting </span></span>RNAs<span> in human AML cell lines. Notably, RNA-sequencing revealed several mRNAs encoding key transcription factors involved in the regulation of myeloid differentiation as targets of hnRNP K. We showed that specific sequence motifs confer the interaction of </span></span><span><em>SPI1</em></span> and <span><em>CEBPA</em></span><span> 5′ and 3′UTRs with hnRNP K. The siRNA mediated reduction of hnRNP K in human AML cells resulted in an increase of PU.1 and C/EBPα that is most pronounced for the p30 isoform. The combinatorial treatment with the inducer of myeloid differentiation valproic acid resulted in increased C/EBPα expression and myeloid differentiation. Together, our results indicate that hnRNP K post-transcriptionally regulates the expression of myeloid master transcription factors. These novel findings can inaugurate novel options for targeted treatment of AML del(9q) by modulation of hnRNP K function.</span></p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 1","pages":"Article 195004"},"PeriodicalIF":4.7,"publicationDate":"2023-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138441701","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
Modulation of Krüppel-like factors (KLFs) interaction with their binding partners in cancers through acetylation and phosphorylation 通过乙酰化和磷酸化调节癌症中kr<s:1> ppel样因子(KLFs)与其结合伙伴的相互作用。
IF 4.7 3区 生物学
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-11-20 DOI: 10.1016/j.bbagrm.2023.195003
Kanupriya Jha , Amit Kumar , Kartik Bhatnagar , Anupam Patra , Neel Sarovar Bhavesh , Bipin Singh , Sarika Chaudhary
{"title":"Modulation of Krüppel-like factors (KLFs) interaction with their binding partners in cancers through acetylation and phosphorylation","authors":"Kanupriya Jha ,&nbsp;Amit Kumar ,&nbsp;Kartik Bhatnagar ,&nbsp;Anupam Patra ,&nbsp;Neel Sarovar Bhavesh ,&nbsp;Bipin Singh ,&nbsp;Sarika Chaudhary","doi":"10.1016/j.bbagrm.2023.195003","DOIUrl":"10.1016/j.bbagrm.2023.195003","url":null,"abstract":"<div><p><span>Post-translational modifications (PTMs) of transcription factors regulate transcriptional activity and play a key role in essentially all biological processes<span><span> and generate indispensable insight towards biological function including activity state, subcellular localization, protein solubility, protein folding, substrate trafficking, and protein-protein interactions. </span>Amino acids modified chemically via PTMs, function as molecular switches and affect the protein function and characterization and increase the </span></span>proteome<span><span> complexity. Krüppel-like transcription factors (KLFs) control essential cellular processes including proliferation, differentiation, migration, programmed cell death and various cancer-relevant processes. We investigated the interactions of KLF group-2 members with their binding partners to assess the role of acetylation and phosphorylation in KLFs on their </span>binding affinity. It was observed that acetylation and phosphorylation at different positions in KLFs have a variable effect on binding with specific partners. KLF2-EP300, KLF4-SP1, KLF6-ATF3, KLF6-JUN, and KLF7-JUN show stabilization upon acetylation or phosphorylation at variable positions. On the other hand, KLF4-CBP, KLF4-EP300, KLF5-CBP, KLF5-WWP1, KLF6-SP1, and KLF7-ATF3 show stabilization or destabilization due to acetylation or phosphorylation at variable positions in KLFs. This provides a molecular explanation of the experimentally observed dual role of KLF group-2 members as a suppressor or activator of cancers in a PTM-dependent manner.</span></p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 1","pages":"Article 195003"},"PeriodicalIF":4.7,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138296626","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 association of the RSC remodeler complex with chromatin is influenced by the prefoldin-like Bud27 and determines nucleosome positioning and polyadenylation sites usage in Saccharomyces cerevisiae RSC重塑复合体与染色质的关联受前折叠蛋白样Bud27的影响,并决定了酿酒酵母中核小体的定位和聚腺苷化位点的使用。
IF 4.7 3区 生物学
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-11-13 DOI: 10.1016/j.bbagrm.2023.194995
Abel Cuevas-Bermúdez , Verónica Martínez-Fernández , Ana I. Garrido-Godino , Antonio Jordán-Pla , Xenia Peñate , Manuel Martín-Expósito , Gabriel Gutiérrez , Chhabi K. Govind , Sebastián Chávez , Vicent Pelechano , Francisco Navarro
{"title":"The association of the RSC remodeler complex with chromatin is influenced by the prefoldin-like Bud27 and determines nucleosome positioning and polyadenylation sites usage in Saccharomyces cerevisiae","authors":"Abel Cuevas-Bermúdez ,&nbsp;Verónica Martínez-Fernández ,&nbsp;Ana I. Garrido-Godino ,&nbsp;Antonio Jordán-Pla ,&nbsp;Xenia Peñate ,&nbsp;Manuel Martín-Expósito ,&nbsp;Gabriel Gutiérrez ,&nbsp;Chhabi K. Govind ,&nbsp;Sebastián Chávez ,&nbsp;Vicent Pelechano ,&nbsp;Francisco Navarro","doi":"10.1016/j.bbagrm.2023.194995","DOIUrl":"10.1016/j.bbagrm.2023.194995","url":null,"abstract":"<div><p><span>The tripartite interaction between the chromatin remodeler complex RSC, RNA<span><span> polymerase subunit Rpb5 and prefoldin-like Bud27 is necessary for proper RNA pol II elongation. Indeed lack of Bud27 alters this association and affects transcription elongation. This work investigates the consequences of lack of Bud27 on the chromatin association of RSC and RNA pol II, and on </span>nucleosome positioning. Our results demonstrate that RSC binds chromatin in gene bodies and lack of Bud27 alters this association, mainly around polyA sites. This alteration impacts chromatin organization and leads to the accumulation of RNA pol II molecules around polyA sites, likely due to pausing or arrest. Our data suggest that RSC is necessary to maintain chromatin organization around those sites, and any alteration of this organization results in the widespread use of alternative polyA sites. Finally, we also find a similar molecular phenotype that occurs upon TOR inhibition with rapamycin, which suggests that alternative </span></span>polyadenylation observed upon TOR inhibition is likely Bud27-dependent.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 1","pages":"Article 194995"},"PeriodicalIF":4.7,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134650487","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 poly-histidine motif of HOXA1 is involved in regulatory interactions with cysteine-rich proteins HOXA1的多组氨酸基序参与与富含半胱氨酸的蛋白的调节相互作用。
IF 4.7 3区 生物学
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-11-11 DOI: 10.1016/j.bbagrm.2023.194993
Damien Marchese, Florent Guislain, Tamara Pringels, Laure Bridoux, René Rezsohazy
{"title":"A poly-histidine motif of HOXA1 is involved in regulatory interactions with cysteine-rich proteins","authors":"Damien Marchese,&nbsp;Florent Guislain,&nbsp;Tamara Pringels,&nbsp;Laure Bridoux,&nbsp;René Rezsohazy","doi":"10.1016/j.bbagrm.2023.194993","DOIUrl":"10.1016/j.bbagrm.2023.194993","url":null,"abstract":"<div><p><span>Homopolymeric amino acid repeats<span> are found in about 24 % of human proteins and are over-represented in transcriptions factors and kinases. Although relatively rare, homopolymeric histidine repeats (polyH) are more significantly found in proteins involved in the regulation of </span></span>embryonic development<span>. To gain a better understanding of the role of polyH in these proteins, we used a bioinformatic approach to search for shared features in the interactomes of polyH-containing proteins in human. Our analysis revealed that polyH protein interactomes are enriched in cysteine-rich proteins and in proteins containing (a) cysteine repeat(s). Focusing on HOXA1, a HOX transcription factor displaying one long polyH motif, we identified that the polyH motif is required for the HOXA1 interaction with such cysteine-rich proteins. We observed a correlation between the length of the polyH repeat and the strength of the HOXA1 interaction with one Cys-rich protein, MDFI. We also found that metal ion chelators disrupt the HOXA1-MDFI interaction supporting that such metal ions are required for the interaction. Furthermore, we identified three polyH interactors which down-regulate the transcriptional activity of HOXA1. Taken together, our data point towards the involvement of polyH and cysteines in regulatory interactions between proteins, notably transcription factors like HOXA1.</span></p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 1","pages":"Article 194993"},"PeriodicalIF":4.7,"publicationDate":"2023-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89720656","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
Isolation and characterisation of promoters from mouse genome to drive post-meiotic germ cell-specific robust gene expression for functional genomics studies 从小鼠基因组中分离和鉴定启动子,以驱动减数分裂后生殖细胞特异性健壮基因表达,用于功能基因组学研究。
IF 4.7 3区 生物学
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-11-11 DOI: 10.1016/j.bbagrm.2023.194994
Abhishek Das , Srimoyee Koner , Subeer S. Majumdar , Nirmalya Ganguli
{"title":"Isolation and characterisation of promoters from mouse genome to drive post-meiotic germ cell-specific robust gene expression for functional genomics studies","authors":"Abhishek Das ,&nbsp;Srimoyee Koner ,&nbsp;Subeer S. Majumdar ,&nbsp;Nirmalya Ganguli","doi":"10.1016/j.bbagrm.2023.194994","DOIUrl":"10.1016/j.bbagrm.2023.194994","url":null,"abstract":"<div><p><span>The generation of spermatozoa from developing germ cells through mitotic and meiotic divisions is a highly regulated and complex process. Any defect in this process, may lead to subfertility/infertility. The role of different transcripts (mRNA/miRNA/lncRNA) in regulation of the pre-meiotic, meiotic, and post-meiotic stages of spermatogenesis<span> are being proposed based on various multiomics based approaches. Such differential gene-expression is regulated by promoter elements that are activated in a stage specific manner. To determine the role of these differentially expressed transcripts in the process of meiosis, a robust post-meiotic germ cell specific promoter is required. In the present study, we have isolated and characterized the expression of the mouse Proacrosin, SP10, and ELP<span> promoters for driving post-meiotic germ cell specific gene-expression. Promoter regions of all these 3 genes were isolated and cloned to generate mammalian expression vector. The transgene expression in post-meiotic germ cells was assessed in mice using the testicular electroporation method </span></span></span><em>in vitro</em> as well as <em>in vivo</em><span>, using above promoters. It was also validated in goat seminiferous tubules, </span><em>in vitro</em>. We have also carried out a comparative analysis of the strength of these promoters to confirm their robustness that indicated Proacrosin to be the most robust promoter that can be useful for diving post-meiotic germ cells specific gene-expression. These promoters can be used to alter gene-expression specifically in post-meiotic germ cells for deciphering the role(s) of germ cell genes in spermatogenic progression or for expressing various genome editing tools for engineering the germ cell genome to understand basis of subfertility/infertility.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1867 1","pages":"Article 194994"},"PeriodicalIF":4.7,"publicationDate":"2023-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92157398","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 functions of FOXP transcription factors and their regulation by post-translational modifications FOXP转录因子的功能及其通过翻译后修饰的调节。
IF 4.7 3区 生物学
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms Pub Date : 2023-10-04 DOI: 10.1016/j.bbagrm.2023.194992
Congwen Gao , Honglin Zhu , Peng Gong , Chen Wu , Xingzhi Xu , Xuefei Zhu
{"title":"The functions of FOXP transcription factors and their regulation by post-translational modifications","authors":"Congwen Gao ,&nbsp;Honglin Zhu ,&nbsp;Peng Gong ,&nbsp;Chen Wu ,&nbsp;Xingzhi Xu ,&nbsp;Xuefei Zhu","doi":"10.1016/j.bbagrm.2023.194992","DOIUrl":"10.1016/j.bbagrm.2023.194992","url":null,"abstract":"<div><p><span><span>The forkhead box subfamily P (FOXP) of transcription factors, consisting of FOXP1, </span>FOXP2, </span>FOXP3<span><span>, and FOXP4, is involved in the regulation of multisystemic functioning. Disruption of the transcriptional activity of FOXP proteins leads to neurodevelopmental disorders and immunological diseases, as well as the suppression or promotion of carcinogenesis. The transcriptional activities of FOXP proteins are directly or indirectly regulated by diverse post-translational modifications, including phosphorylation, ubiquitination, </span>SUMOylation<span><span>, acetylation, O-GlcNAcylation, and </span>methylation. Here, we discuss how post-translational modifications modulate the multiple functions of FOXP proteins and examine the implications for tumorigenesis and cancer therapy.</span></span></p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 4","pages":"Article 194992"},"PeriodicalIF":4.7,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41156288","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
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 ,&nbsp;Subhajit Karmakar ,&nbsp;Malini Basu ,&nbsp;Mrinal K. Ghosh","doi":"10.1016/j.bbagrm.2023.194991","DOIUrl":"10.1016/j.bbagrm.2023.194991","url":null,"abstract":"<div><p><span><span>DDX5 (p68) upregulation has been linked with various cancers of different origins, especially Colon Adenocarcinomas. Similarly, across cancers, </span>MGMT<span> 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 </span></span><em>MGMT</em> gene in the context of colon cancer. This necessitates studying <em>MGMT</em><span> 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 </span><em>MGMT</em> 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 <em>vice-versa</em>. Since p68 cannot directly interact with the MGMT promoter, transcription factors <em>viz.</em><span>, 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 </span><em>via</em> 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 <em>MGMT</em> gene expression.</p></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 ,&nbsp;Valentina Lukinović ,&nbsp;François Charih ,&nbsp;Kyle K. Biggar","doi":"10.1016/j.bbagrm.2023.194990","DOIUrl":"10.1016/j.bbagrm.2023.194990","url":null,"abstract":"<div><p>Proteins play a critical role as key regulators in various biological systems, influencing crucial processes such as gene expression, cell cycle progression<span>, and cellular proliferation<span>. 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<span> 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.</span></span></span></p></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 ,&nbsp;Chen'ang Zhang ,&nbsp;Chengyu Fan,&nbsp;Yanfen Liu","doi":"10.1016/j.bbagrm.2023.194989","DOIUrl":"10.1016/j.bbagrm.2023.194989","url":null,"abstract":"<div><p>Stress granules<span> (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.</span></p></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
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引用次数: 1
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