Transcription-Austin最新文献

{"title":"Hypoxia-inducible transcription factors: architects of tumorigenesis and targets for anticancer drug discovery.","authors":"Alexander McDermott, Ali Tavassoli","doi":"10.1080/21541264.2024.2417475","DOIUrl":"10.1080/21541264.2024.2417475","url":null,"abstract":"<p><p>Hypoxia-inducible factors (HIFs) play a pivotal role as master regulators of tumor survival and growth, controlling a wide array of cellular processes in response to hypoxic stress. Clinical data correlates upregulated HIF-1 and HIF-2 levels with an aggressive tumor phenotype and poor patient outcome. Despite extensive validation as a target in cancer, pharmaceutical targeting of HIFs, particularly the interaction between α and βsubunits that forms the active transcription factor, has proved challenging. Nonetheless, many indirect inhibitors of HIFs have been identified, targeting diverse parts of this pathway. Significant strides have also been made in the development of direct inhibitors of HIF-2, exemplified by the FDA approval of Belzutifan for the treatment of metastatic clear cell renal carcinoma. While efforts to target HIF-1 using various therapeutic modalities have shown promise, no clinical candidates have yet emerged. This review aims to provide insights into the intricate and extensive role played by HIFs in cancer, and the ongoing efforts to develop therapeutic agents against this target.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"1-32"},"PeriodicalIF":3.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From silence to symphony: transcriptional repression and recovery in response to DNA damage.","authors":"Kamal Ajit, Monika Gullerova","doi":"10.1080/21541264.2024.2406717","DOIUrl":"https://doi.org/10.1080/21541264.2024.2406717","url":null,"abstract":"<p><p>Genotoxic stress resulting from DNA damage is resolved through a signaling cascade known as the DNA Damage Response (DDR). The repair of damaged DNA is essential for cell survival, often requiring the DDR to attenuate other cellular processes such as the cell cycle, DNA replication, and transcription of genes not involved in DDR. The complex relationship between DDR and transcription has only recently been investigated. Transcription can facilitate the DDR in response to double-strand breaks (DSBs) and stimulate nucleotide excision repair (NER). However, transcription may need to be reduced to prevent potential interference with the repair machinery. In this review, we discuss various mechanisms that regulate transcription repression in response to different types of DNA damage, categorizing them by their range and duration of effect. Finally, we explore various models of transcription recovery following DNA damage-induced repression.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"1-15"},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure and function of bacterial transcription regulators of the SorC family.","authors":"Markéta Šoltysová, Pavlína Řezáčová","doi":"10.1080/21541264.2024.2387895","DOIUrl":"https://doi.org/10.1080/21541264.2024.2387895","url":null,"abstract":"<p><p>The SorC family is a large group of bacterial transcription regulators involved in controlling carbohydrate catabolism and quorum sensing. SorC proteins consist of a conserved C-terminal effector-binding domain and an N-terminal DNA-binding domain, whose type divides the family into two subfamilies: SorC/DeoR and SorC/CggR. Proteins of the SorC/CggR subfamily are known to regulate the key node of glycolysis-triose phosphate interconversion. On the other hand, SorC/DeoR proteins are involved in a variety of peripheral carbohydrate catabolic pathways and quorum sensing functions, including virulence. Despite the abundance and importance of this family, SorC proteins seem to be on the periphery of scientific interest, which might be caused by the fragmentary information about its representatives. This review aims to compile the existing knowledge and provide material to inspire future questions about the SorC protein family.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"1-22"},"PeriodicalIF":3.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the dynamic code: DNA recognition by transcription factors in the ever-changing genome.","authors":"Yumi Minyi Yao, Irina Miodownik, Michael P O'Hagan, Muhammad Jbara, Ariel Afek","doi":"10.1080/21541264.2024.2379161","DOIUrl":"https://doi.org/10.1080/21541264.2024.2379161","url":null,"abstract":"<p><p>Transcription factors (TFs) intricately navigate the vast genomic landscape to locate and bind specific DNA sequences for the regulation of gene expression programs. These interactions occur within a dynamic cellular environment, where both DNA and TF proteins experience continual chemical and structural perturbations, including epigenetic modifications, DNA damage, mechanical stress, and post-translational modifications (PTMs). While many of these factors impact TF-DNA binding interactions, understanding their effects remains challenging and incomplete. This review explores the existing literature on these dynamic changes and their potential impact on TF-DNA interactions.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"1-25"},"PeriodicalIF":3.6,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Negative feedback systems for modelling NF-κB transcription factor oscillatory activity.","authors":"Bonawentura Kochel","doi":"10.1080/21541264.2024.2331887","DOIUrl":"https://doi.org/10.1080/21541264.2024.2331887","url":null,"abstract":"<p><p>Low-dimensional negative feedback systems (NFSs) were developed within a signal flow model to describe the oscillatory activities of NF-κB caused by interactions with its inhibitor IκBα. The NFSs were established as 3^rd- and 4^th-order linear systems containing unperturbed and perturbed negative feedback (NF) loops with constant or time-varying NF strengths and a feed-forward loop. NF-related analytical solutions to the NFSs representing the time courses of NF-κB and IκBα were determined and their exact mathematical relationship was found. The NFS's parameters were determined to fit the experimental time courses of NF-κB in TNF-α-stimulated embryonic fibroblasts, <i>rela</i>^-/- embryonic fibroblasts reconstituted with RelA, C9L cells, GFP-p65 knock-in embryonic fibroblasts and embryogenic fibroblasts lacking Iκβ and IκBε, LPS-stimulated IC-21 macrophages treated or not with DCPA, and anti-IgM-stimulated DT40 B-lymphocytes. The unperturbed and perturbed NFSs describing the above biosystems generated isochronous and non-isochronous solutions, depending on a constant or time-varying NF strength, respectively. The oscillation period of the NF-coupled solutions, the phase difference between them and the time delays in the appearance of cytoplasmic IκBα after stimulation of NF-κB were determined. A significant divergence between the IκBα solutions to the NFSs and the IκBα experimental courses led to a rejection of the NF coupling between NF-κB and IκBα in the above biosystems. It was shown that neither the linearity nor the low dimensionality of the NFSs altered the NF relationship and the divergence between the IκBα solutions to the NFS and IκBα experimental time courses. Although the NF relationship between IκBα and NF-κB was not confirmed in all the experimental data analyzed, delayed negative feedback was found in some cases.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"1-32"},"PeriodicalIF":3.6,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140913092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Minimization and complete loss of general transcription factor proteins in the intracellular parasite <i>Encephalitozoon cuniculi</i>.","authors":"Alana E Belkevich, Andrew Y Khalil, Wayne A Decatur, Ryan J Palumbo, Bruce A Knutson","doi":"10.1080/21541264.2024.2350162","DOIUrl":"https://doi.org/10.1080/21541264.2024.2350162","url":null,"abstract":"<p><p>Genome compaction is a common evolutionary feature of parasites. The unicellular, obligate intracellular parasite <i>Encephalitozoon cuniculi</i> has one of smallest known eukaryotic genomes, and is nearly four times smaller than its distant fungi relative, the budding yeast <i>Saccharomyces cerevisiae</i>. Comparison of the proteins encoded by compacted genomes to those encoded by larger genomes can reveal the most highly conserved features of the encoded proteins. In this study, we identified the proteins comprising the RNA polymerases and their corresponding general transcription factors by using several bioinformatic approaches to compare the transcription machinery of <i>E. cuniculi</i> and <i>S. cerevisiae</i>. Surprisingly, our analyses revealed an overall reduction in the size of the proteins comprising transcription machinery of <i>E. cuniculi</i>, which includes the loss of entire regions or functional domains from proteins, as well as the loss of entire proteins and complexes. Unexpectedly, we found that the <i>E. cuniculi</i> ortholog of Rpc37 (a RNA Polymerase III subunit) more closely resembles the <i>H. sapiens</i> ortholog of Rpc37 than the <i>S. cerevisiae</i> ortholog of Rpc37, in both size and structure. Overall, our findings provide new insight into the minimal core eukaryotic transcription machinery and help define the most critical features of Pol components and general transcription factors.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"1-17"},"PeriodicalIF":3.6,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aryl hydrocarbon receptor as a drug target in advanced prostate cancer therapy - obstacles and perspectives.","authors":"Jiřina Procházková, Zuzana Kahounová, Jan Vondráček, Karel Souček","doi":"10.1080/21541264.2024.2334106","DOIUrl":"https://doi.org/10.1080/21541264.2024.2334106","url":null,"abstract":"<p><p>Aryl hydrocarbon receptor (AhR) is a transcription factor that is primarily known as an intracellular sensor of environmental pollution. After five decades, the list of synthetic and toxic chemicals that activate AhR signaling has been extended to include a number of endogenous compounds produced by various types of cells via their metabolic activity. AhR signaling is active from the very beginning of embryonal development throughout the life cycle and participates in numerous biological processes such as control of cell proliferation and differentiation, metabolism of aromatic compounds of endogenous and exogenous origin, tissue regeneration and stratification, immune system development and polarization, control of stemness potential, and homeostasis maintenance. AhR signaling can be affected by various pharmaceuticals that may help modulate abnormal AhR signaling and drive pathological states. Given their role in immune system development and regulation, AhR antagonistic ligands are attractive candidates for immunotherapy of disease states such as advanced prostate cancer, where an aberrant immune microenvironment contributes to cancer progression and needs to be reeducated. Advanced stages of prostate cancer are therapeutically challenging and characterized by decreased overall survival (OS) due to the metastatic burden. Therefore, this review addresses the role of AhR signaling in the development and progression of prostate cancer and discusses the potential of AhR as a drug target for the treatment of advanced prostate cancer upon entering the phase of drug resistance and failure of first-line androgen deprivation therapy.<b>Abbreviation</b>: ADC: antibody-drug conjugate; ADT: androgen deprivation therapy; AhR: aryl hydrocarbon receptor; AR: androgen receptor; ARE: androgen response element; ARPI: androgen receptor pathway inhibitor; mCRPC: metastatic castration-resistant prostate cancer; DHT: 5a-dihydrotestosterone; FICZ: 6-formylindolo[3,2-b]carbazole; 3-MC: 3-methylcholanthrene; 6-MCDF: 6-methyl-1,3,8-trichlorodibenzofuran; MDSCs: myeloid-derived suppressor cells; PAHs: polycyclic aromatic hydrocarbons; PCa: prostate cancer; TAMs: tumor-associated macrophages; TF: transcription factor; TCDD, 2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxin; TME: tumor microenvironment; TRAMP: transgenic adenocarcinoma of the mouse prostate; TROP2: tumor associated calcium signal transducer 2.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"1-20"},"PeriodicalIF":3.6,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140319480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA polymerase collisions and their role in transcription.","authors":"Ling Wang","doi":"10.1080/21541264.2024.2316972","DOIUrl":"10.1080/21541264.2024.2316972","url":null,"abstract":"<p><p>RNA polymerases are the central enzymes of gene expression and function frequently in either a head-on or co-directional manner on the busy DNA track. Whether and how these collisions between RNA polymerases contribute to transcriptional regulation is mysterious. Increasing evidence from biochemical and single-molecule studies suggests that RNA polymerase collisions function as an important regulator to fine-tune transcription, rather than creating deleterious \"traffic jams\". This review summarizes the recent progress on elucidating the consequences of RNA polymerase collisions during transcription and highlights the significance of cooperation and coordination between RNA polymerases.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"38-47"},"PeriodicalIF":3.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11093029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139736350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacterial phenotypic heterogeneity through the lens of single-cell RNA sequencing.","authors":"Alex W Walls, Adam Z Rosenthal","doi":"10.1080/21541264.2024.2334110","DOIUrl":"10.1080/21541264.2024.2334110","url":null,"abstract":"<p><p>Bacterial transcription is not monolithic. Microbes exist in a wide variety of cell states that help them adapt to their environment, acquire and produce essential nutrients, and engage in both competition and cooperation with their neighbors. While we typically think of bacterial adaptation as a group behavior, where all cells respond in unison, there is often a mixture of phenotypic responses within a bacterial population, where distinct cell types arise. A primary phenomenon driving these distinct cell states is transcriptional heterogeneity. Given that bacterial mRNA transcripts are extremely short-lived compared to eukaryotes, their transcriptional state is closely associated with their physiology, and thus the transcriptome of a bacterial cell acts as a snapshot of the behavior of that bacterium. Therefore, the application of single-cell transcriptomics to microbial populations will provide novel insight into cellular differentiation and bacterial ecology. In this review, we provide an overview of transcriptional heterogeneity in microbial systems, discuss the findings already provided by single-cell approaches, and plot new avenues of inquiry in transcriptional regulation, cellular biology, and mechanisms of heterogeneity that are made possible when microbial communities are analyzed at single-cell resolution.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"48-62"},"PeriodicalIF":3.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11093040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140294946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maintaining transcriptional homeostasis during cell cycle.","authors":"Lucía Ramos-Alonso, Pierre Chymkowitch","doi":"10.1080/21541264.2023.2246868","DOIUrl":"10.1080/21541264.2023.2246868","url":null,"abstract":"<p><p>The preservation of gene expression patterns that define cellular identity throughout the cell division cycle is essential to perpetuate cellular lineages. However, the progression of cells through different phases of the cell cycle severely disrupts chromatin accessibility, epigenetic marks, and the recruitment of transcriptional regulators. Notably, chromatin is transiently disassembled during S-phase and undergoes drastic condensation during mitosis, which is a significant challenge to the preservation of gene expression patterns between cell generations. This article delves into the specific gene expression and chromatin regulatory mechanisms that facilitate the preservation of transcriptional identity during replication and mitosis. Furthermore, we emphasize our recent findings revealing the unconventional role of yeast centromeres and mitotic chromosomes in maintaining transcriptional fidelity beyond mitosis.</p>","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"1-21"},"PeriodicalIF":3.6,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11093055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10132578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}