Biochimica et Biophysica Acta-Gene Regulatory Mechanisms最新文献

{"title":"TRIM25-mediated ubiquitination of G3BP1 regulates the proliferation and migration of human neuroblastoma cells","authors":"Yun Yang ,&nbsp;Yanyan Luo ,&nbsp;Cong Yang ,&nbsp;Ronggui Hu ,&nbsp;Xiong Qin ,&nbsp;Chuanyin Li","doi":"10.1016/j.bbagrm.2023.194954","DOIUrl":"10.1016/j.bbagrm.2023.194954","url":null,"abstract":"<div><p><span>Neuroblastoma is one of the most severe malignant tumors and accounts for substantial cancer-related mortality in children. Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is highly expressed in various cancers and acts as an important biomarker of poor prognosis. The ablation of G3BP1 inhibited the proliferation and migration of human SHSY5Y cells. Because of its important role in neuroblastoma, the regulation of G3BP1 protein homeostasis<span> was probed. TRIM25, which belongs to the tripartite motif (TRIM) family of proteins, was identified as an interacting partner for G3BP1 using the yeast two-hybrid (Y2H) method. TRIM25 mediates the ubiquitination of G3BP1 at multiple sites and stabilizes its protein level. Then, our study found that TRIM25 knockdown also inhibited the proliferation and migration of neuroblastoma cells. The TRIM25 and G3BP1 double knockdown SHSY5Y cell line was generated, and double knockdown cells exhibited lower proliferation and migration ability than cells with only TRIM25 or G3BP1 knockdown. Further study demonstrated that TRIM25 promotes the proliferation and migration of neuroblastoma cells in a G3BP1-dependent manner. Tumor xenograft assays indicated that the ablation of TRIM25 and G3BP1 synergistically suppressed the tumorigenicity of neuroblastoma cells in </span></span>nude mice<span>, and TRIM25 promoted the tumorigenicity of G3BP1 intact SHSY5Y cells but not G3BP1 knockout cells. Thus, TRIM25 and G3BP1, two oncogenic genes, are suggested as potential therapeutic targets for neuroblastoma.</span></p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 3","pages":"Article 194954"},"PeriodicalIF":4.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10039415","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}

{"title":"The yeast mRNA-binding protein Cth2 post-transcriptionally modulates ergosterol biosynthesis in response to iron deficiency","authors":"Tania Jordá ,&nbsp;Nicolas Rozès ,&nbsp;María Teresa Martínez-Pastor ,&nbsp;Sergi Puig","doi":"10.1016/j.bbagrm.2023.194959","DOIUrl":"10.1016/j.bbagrm.2023.194959","url":null,"abstract":"<div><p>Sterol synthesis is an iron-dependent metabolic pathway in eukaryotes. Consequently, fungal ergosterol biosynthesis (ERG) is down-regulated in response to iron deficiency. In this report, we show that, upon iron limitation or overexpression of the iron-regulated mRNA-binding protein Cth2, the yeast <em>Saccharomyces cerevisiae</em> down-regulates the three initial enzymatic steps of ergosterol synthesis (<em>ERG1</em>, <em>ERG7</em> and <em>ERG11</em>). Mechanistically, we show that Cth2 protein limits the translation and promotes the decrease in the mRNA levels of these specific <em>ERG</em> genes, which contain consensus Cth2-binding sites defined as AU-rich elements (AREs). Thus, expression of <em>CTH2</em> leads to the accumulation of initial sterol intermediates, such as squalene, and to the drop of ergosterol levels. Changes in <em>CTH2</em> expression levels disturb the response of yeast cells to stresses related to membrane integrity such as high ethanol and sorbitol concentrations. Therefore, <em>CTH2</em> should be considered as a critical regulatory factor of ergosterol biosynthesis during iron deficiency.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 3","pages":"Article 194959"},"PeriodicalIF":4.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10412441","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}

{"title":"Differences and similarities in recognition of co-factors by Taf14","authors":"Minh Chau Nguyen ,&nbsp;Duo Wang ,&nbsp;Brianna J. Klein ,&nbsp;Yong Chen ,&nbsp;Tatiana G. Kutateladze","doi":"10.1016/j.bbagrm.2023.194961","DOIUrl":"10.1016/j.bbagrm.2023.194961","url":null,"abstract":"<div><p>Taf14<span> is a subunit of multiple fundamental complexes implicated in transcriptional regulation and DNA damage repair in yeast cells. Here, we investigate the association of Taf14 with the consensus sequence present in other subunits of these complexes and describe the mechanistic features that affect this association. We demonstrate that the precise molecular mechanisms and biological outcomes underlying the Taf14 interactions depend on the accessibility of binding interfaces, the ability to recognize other ligands, and a degree of sensitivity to temperature and chemical and osmotic stresses. Our findings aid in a better understanding of how the distribution of Taf14 among the complexes is mediated.</span></p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 3","pages":"Article 194961"},"PeriodicalIF":4.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10039967","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}

{"title":"Dynamics of epigenetic control in plants via SET domain containing proteins: Structural and functional insights","authors":"Sushmita Seni ,&nbsp;Roshan Kumar Singh ,&nbsp;Manoj Prasad","doi":"10.1016/j.bbagrm.2023.194966","DOIUrl":"10.1016/j.bbagrm.2023.194966","url":null,"abstract":"<div><p><span>Plants control expression of their genes in a way that involves manipulating the chromatin structural dynamics in order to adapt to environmental changes and carry out developmental processes. Histone modifications like </span>histone methylation<span><span><span> are significant epigenetic marks which profoundly and globally modify chromatin, potentially affecting the expression of several genes. </span>Methylation<span><span><span> of histones is catalyzed by histone lysine </span>methyltransferases (HKMTs), that features an evolutionary conserved domain known as SET [Su(var)3–9, E(Z), Trithorax]. This methylation is directed at particular lysine (K) residues on H3 or </span>H4 histone. Plant SET domain group (SDG) proteins are categorized into different classes that have been conserved through evolution, and each class have specificity that influences how the </span></span>chromatin structure<span> operates. The domains discovered in plant SET domain proteins have typically been linked to protein-protein interactions, suggesting that majority of the SDGs function in complexes. Additionally, SDG-mediated histone mark deposition also affects alternative splicing events. In present review, we discussed the diversity of SDGs in plants including their structural properties. Additionally, we have provided comprehensive summary of the functions of the SDG-domain containing proteins in plant developmental processes and response to environmental stimuli have also been highlighted.</span></span></p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 3","pages":"Article 194966"},"PeriodicalIF":4.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10394478","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}

{"title":"Histone variant H2B.Z acetylation is necessary for maintenance of Toxoplasma gondii biological fitness","authors":"Laura Vanagas ,&nbsp;Daniela Muñoz ,&nbsp;Constanza Cristaldi ,&nbsp;Agustina Ganuza ,&nbsp;Rosario Nájera ,&nbsp;Mabel C. Bonardi ,&nbsp;Valeria R. Turowski ,&nbsp;Fanny Guzman ,&nbsp;Bin Deng ,&nbsp;Kami Kim ,&nbsp;William J. Sullivan Jr ,&nbsp;Sergio O. Angel","doi":"10.1016/j.bbagrm.2023.194943","DOIUrl":"10.1016/j.bbagrm.2023.194943","url":null,"abstract":"<div><p><span><span>Through regulation of DNA packaging<span><span>, histone proteins are fundamental to a wide array of </span>biological processes<span><span>. A variety of post-translational modifications (PTMs), including acetylation, constitute a proposed </span>histone code that is interpreted by “reader” proteins to modulate </span></span></span>chromatin structure. Canonical histones can be replaced with variant versions that add an additional layer of regulatory complexity. The protozoan parasite </span><span><em>Toxoplasma gondii</em></span> is unique among eukaryotes in possessing a novel variant of H2B designated H2B.Z. The combination of PTMs and the use of histone variants are important for gene regulation in <em>T. gondii</em>, offering new targets for drug development. In this work, <em>T. gondii</em><span> parasites were generated in which the 5 N-terminal acetylatable lysines in H2B.Z were mutated to either alanine<span> (c-Myc-A) or arginine (c-Myc-R). The c-Myc-A mutant displayed no phenotype over than a mild defect in its ability to kill mice. The c-Myc-R mutant presented an impaired ability to grow and an increase in differentiation to latent bradyzoites. The c-Myc-R mutant was also more sensitive to DNA damage, displayed no virulence in mice, and provided protective immunity against future infection. While nucleosome composition was unaltered, key genes were abnormally expressed during </span></span><em>in vitro</em> bradyzoite differentiation. Our results show that regulation of the N-terminal positive charge patch of H2B.Z is important for these processes. We also show that acetylated N-terminal H2B.Z interacts with some unique proteins compared to its unacetylated counterpart; the acetylated peptide pulled down proteins associated with chromosome maintenance/segregation and cell cycle, suggesting a link between H2B.Z acetylation status and mitosis.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 3","pages":"Article 194943"},"PeriodicalIF":4.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10524646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10093812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ubiquitination is a major modulator for the activation of inflammasomes and pyroptosis","authors":"Qiuyun Jiang ,&nbsp;Zhigang Zhu ,&nbsp;Xinliang Mao","doi":"10.1016/j.bbagrm.2023.194955","DOIUrl":"10.1016/j.bbagrm.2023.194955","url":null,"abstract":"<div><p><span>Inflammasomes are a central node of the innate immune defense system against the threat of homeostatic perturbance caused by pathogenic organisms or host-derived molecules. Inflammasomes are generally composed of multimeric </span>protein complexes<span> that assemble in the cytosol after sensing danger signals. Activated inflammasomes promote downstream proteolytic activation, which triggers the release of pro-inflammatory cytokines therefore inducing pyroptotic cell death<span>. The inflammasome pathway is finely tuned by various mechanisms. Recent studies found that protein post-translational modifications such as ubiquitination also modulate inflammasome activation. Targeting the ubiquitination modification of the inflammasome pathway might be a promising strategy for related diseases. In this review, we extensively discuss the advances in inflammasome activation and pyroptosis modulated by ubiquitination which help in-depth understanding and controlling the inflammasome and pyroptosis in various diseases.</span></span></p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 3","pages":"Article 194955"},"PeriodicalIF":4.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10034506","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}

{"title":"New roles for elongation factors in RNA polymerase II ubiquitylation and degradation","authors":"Joseph C. Reese","doi":"10.1016/j.bbagrm.2023.194956","DOIUrl":"10.1016/j.bbagrm.2023.194956","url":null,"abstract":"<div><p>RNA polymerase II<span><span> (RNAPII) encounters numerous impediments on its way to completing mRNA synthesis across a gene. Paused and arrested RNAPII are reactivated or rescued by </span>elongation factors<span><span> that travel with polymerase as it transcribes </span>DNA. However, when RNAPII fails to resume transcription, such as when it encounters an unrepairable bulky DNA lesion, it is removed by the targeting of its largest subunit, Rpb1, for degradation by the ubiquitin-proteasome system (UPS). We are starting to understand this process better and how the UPS marks Rbp1 for degradation. This review will focus on the latest developments and describe new functions for elongation factors that were once thought to only promote elongation in unstressed conditions in the removal and degradation of RNAPII. I propose that in addition to changes in RNAPII structure, the composition and modification of elongation factors in the elongation complex determine whether to rescue or degrade RNAPII.</span></span></p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 3","pages":"Article 194956"},"PeriodicalIF":4.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10527621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10039435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allelic variation within the major APOE CpG island affects its methylation in the brain of targeted replacement mice expressing human APOE","authors":"Johanna Rueter,&nbsp;Gerald Rimbach,&nbsp;Patricia Huebbe","doi":"10.1016/j.bbagrm.2023.194942","DOIUrl":"10.1016/j.bbagrm.2023.194942","url":null,"abstract":"<div><p></p><ul><li><span>•</span><span><p><span>The number of cytosine-phosphate-guanine (CpG) sites differs due to sequence variation in the human apolipoprotein E (</span><em>APOE</em>) gene.</p></span></li><li><span>•</span><span><p><em>APOE</em> DNA methylation is allele-dependently altered corresponding to the total number of CpG pairs in the brain of APOE targeted replacement mice (<em>APOE εpsilon 4</em> &gt; <em>εpsilon 3</em> &gt; <em>εpsilon 2</em>).</p></span></li><li><span>•</span><span><p>Binding of the methyl-CpG binding protein 2 to genomic <em>APOE</em> was in trend less pronounced in the brain of APOE4 mice.</p></span></li></ul></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 3","pages":"Article 194942"},"PeriodicalIF":4.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10036791","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}

{"title":"A novel endoplasmic reticulum adaptation is critical for the long-lived Caenorhabditis elegans rpn-10 proteasomal mutant","authors":"Meghna N. Chinchankar ,&nbsp;William B. Taylor ,&nbsp;Su-Hyuk Ko ,&nbsp;Ellen C. Apple ,&nbsp;Karl A. Rodriguez ,&nbsp;Lizhen Chen ,&nbsp;Alfred L. Fisher","doi":"10.1016/j.bbagrm.2023.194957","DOIUrl":"10.1016/j.bbagrm.2023.194957","url":null,"abstract":"<div><p><span><span>The loss of proteostasis due to reduced efficiency of </span>protein degradation pathways plays a key role in multiple age-related diseases and is a hallmark of the aging process. Paradoxically, we have previously reported that the </span><span><em>Caenorhabditis elegans</em><em> rpn-10(ok1865)</em></span><span> mutant, which lacks the RPN-10/RPN10/PSMD4 subunit of the 19S regulatory particle of the 26S proteasome<span>, exhibits enhanced cytosolic proteostasis, elevated stress resistance and extended lifespan, despite possessing reduced proteasome function. However, the response of this mutant against threats to endoplasmic reticulum (ER) homeostasis and proteostasis was unknown. Here, we find that the </span></span><em>rpn-10</em><span> mutant is highly ER stress<span> resistant compared to the wildtype. Under unstressed conditions, the ER unfolded protein response (UPR) is activated in the </span></span><em>rpn-10</em> mutant as signified by increased <em>xbp-1</em> splicing. This primed response appears to alter ER homeostasis through the upregulated expression of genes involved in ER protein quality control (ERQC), including those in the ER-associated protein degradation (ERAD) pathway. Pertinently, we find that ERQC is critical for the <em>rpn-10</em> mutant longevity. These changes also alter ER proteostasis, as studied using the <em>C. elegans</em><span> alpha-1 antitrypsin (AAT) deficiency model, which comprises an intestinal ER-localised transgenic reporter of an aggregation-prone form of AAT called ATZ. The </span><em>rpn-10</em> mutant shows a significant reduction in the accumulation of the ATZ reporter, thus indicating that its ER proteostasis is augmented. Via a genetic screen for suppressors of decreased ATZ aggregation in the <em>rpn-10</em> mutant, we then identified <em>ecps-2/H04D03.3</em><span>, a novel ortholog of the proteasome-associated adaptor and scaffold protein ECM29/ECPAS. We further show that </span><em>ecps-2</em> is required for improved ER proteostasis as well as lifespan extension of the <em>rpn-10</em> mutant. Thus, we propose that ECPS-2-proteasome functional interactions, alongside additional putative molecular processes, contribute to a novel ERQC adaptation which underlies the superior proteostasis and longevity of the <em>rpn-10</em> mutant.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 3","pages":"Article 194957"},"PeriodicalIF":4.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10528105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10198101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The fine-tuned crosstalk between lysine acetylation and the circadian rhythm","authors":"Honglv Jiang ,&nbsp;Xiaohui Wang ,&nbsp;Jingjing Ma ,&nbsp;Guoqiang Xu","doi":"10.1016/j.bbagrm.2023.194958","DOIUrl":"10.1016/j.bbagrm.2023.194958","url":null,"abstract":"<div><p><span><span>Circadian rhythm is a roughly 24-h wake and sleep cycle that almost all of the organisms on the earth follow when they execute their biological functions and physiological activities. The circadian clock is mainly regulated by the transcription-translation feedback loop (TTFL), consisting of the core clock proteins, including BMAL1, CLOCK, PERs, CRYs, and a series of accessory factors. The circadian clock and the downstream gene expression are not only controlled at the transcriptional and translational levels but also precisely regulated at the post-translational modification level. Recently, it has been discovered that CLOCK exhibits lysine acetyltransferase activities and could acetylate protein substrates. Core clock proteins are also acetylated, thereby altering their biological functions in the regulation of the expression of downstream genes. Studies have revealed that many </span>protein acetylation<span> events exhibit oscillation behavior. However, the biological function of acetylation on circadian rhythm has only begun to explore. This review will briefly introduce the acetylation and </span></span>deacetylation of the core clock proteins and summarize the proteins whose acetylation is regulated by CLOCK and circadian rhythm. Then, we will also discuss the crosstalk between lysine acetylation and the circadian clock or other post-translational modifications. Finally, we will briefly describe the possible future perspectives in the field.</p></div>","PeriodicalId":55382,"journal":{"name":"Biochimica et Biophysica Acta-Gene Regulatory Mechanisms","volume":"1866 3","pages":"Article 194958"},"PeriodicalIF":4.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10412446","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}