Transcription-Austin最新文献

GATA3 and E2F6 negatively regulate WDR77 expression to inhibit prostate cancer cell growth.

IF 3.6

Transcription-Austin Pub Date : 2025-03-12 DOI: 10.1080/21541264.2025.2476848

Robin Brice, Zhengxin Wang

引用次数: 0

Rho-dependent termination: a bacterial evolutionary capacitor for stress resistance.

IF 3.6

Transcription-Austin Pub Date : 2025-03-05 DOI: 10.1080/21541264.2025.2474367

Sarah B Worthan, Megan I Grant, Megan G Behringer

{"title":"Rho-dependent termination: a bacterial evolutionary capacitor for stress resistance.","authors":"Sarah B Worthan, Megan I Grant, Megan G Behringer","doi":"10.1080/21541264.2025.2474367","DOIUrl":"https://doi.org/10.1080/21541264.2025.2474367","url":null,"abstract":"Since the Modern Synthesis, interest has grown in resolving the \"black box\" between genotype and phenotype. Contained within this black box are highly plastic RNA and proteins with global effects on chromosome integrity and gene expression that serve as evolutionary capacitors - elements that enable the accumulation and buffering of genetic variation in normal conditions and reveal hidden genetic variation when induced by environmental stress. Discussion of evolutionary capacitors has primarily focused on eukaryotic translation factors and chaperones, such as Hsp90 and PSI+ prion. However, due to the coupling of transcription and translation in prokaryotes, transcription factors can be equally impactful in the modulation of gene expression and phenotypes. In this review, we discuss the prokaryotic transcription terminator Rho and how mutagenesis and plasticity of Rho influence epistasis, evolvability, and adaptation to stress in bacteria. We discuss the effects of variation in Rho generated by nature, laboratory mutagenesis, and experimental evolution; and how this variation is constrained or encouraged by Rho's extensive network of protein interactors. Exploring Rho's role as an evolutionary capacitor, along with identifying additional elements that can serve this function, can significantly advance our understanding of how organisms adapt to thrive in diverse environments.","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"1-14"},"PeriodicalIF":3.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568424","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}

引用次数: 0

The role of lncRNA in plant growth and domestication.

IF 3.6

Transcription-Austin Pub Date : 2025-03-04 DOI: 10.1080/21541264.2025.2473224

Vijay Gahlaut, Vandana Jaiswal

引用次数: 0

Harnessing p53 for targeted cancer therapy: new advances and future directions.

IF 3.6

Transcription-Austin Pub Date : 2025-03-03 DOI: 10.1080/21541264.2025.2452711

Zdenek Andrysik, Joaquin M Espinosa

{"title":"Harnessing p53 for targeted cancer therapy: new advances and future directions.","authors":"Zdenek Andrysik, Joaquin M Espinosa","doi":"10.1080/21541264.2025.2452711","DOIUrl":"https://doi.org/10.1080/21541264.2025.2452711","url":null,"abstract":"The transcription factor p53 is the most frequently impaired tumor suppressor in human cancers. In response to various stress stimuli, p53 activates transcription of genes that mediate its tumor-suppressive functions. Distinctive characteristics of p53 outlined here enable a well-defined program of genes involved in cell cycle arrest, apoptosis, senescence, differentiation, metabolism, autophagy, DNA repair, anti-viral response, and anti-metastatic functions, as well as facilitating autoregulation within the p53 network. This versatile, anti-cancer network governed chiefly by a single protein represents an immense opportunity for targeted cancer treatment, since about half of human tumors retain unmutated p53. During the last two decades, numerous compounds have been developed to block the interaction of p53 with the main negative regulator MDM2. However, small molecule inhibitors of MDM2 only induce a therapeutically desirable apoptotic response in a limited number of cancer types. Moreover, clinical trials of the MDM2 inhibitors as monotherapies have not met expectations and have revealed hematological toxicity as a characteristic adverse effect across this drug class. Currently, combination treatments are the leading strategy for enhancing efficacy and reducing adverse effects of MDM2 inhibitors. This review summarizes efforts to identify and test therapeutics that work synergistically with MDM2 inhibitors. Two main types of drugs have emerged among compounds used in the following combination treatments: first, modulators of the p53-regulated transcriptome (including chromatin modifiers), translatome, and proteome, and second, drugs targeting the downstream pathways such as apoptosis, cell cycle arrest, DNA repair, metabolic stress response, immune response, ferroptosis, and growth factor signaling. Here, we review the current literature in this field, while also highlighting overarching principles that could guide target selection in future combination treatments.","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"1-44"},"PeriodicalIF":3.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543957","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}

引用次数: 0

Harnessing transcription factors for therapeutic purposes.

IF 3.6

Transcription-Austin Pub Date : 2025-02-14 DOI: 10.1080/21541264.2025.2460249

Joaquin M Espinosa

引用次数: 0

Beyond small molecules: advancing MYC-targeted cancer therapies through protein engineering.

IF 3.6

Transcription-Austin Pub Date : 2025-01-29 DOI: 10.1080/21541264.2025.2453315

Rama Edaibis, Raneem Akel, Jumi A Shin

{"title":"Beyond small molecules: advancing MYC-targeted cancer therapies through protein engineering.","authors":"Rama Edaibis, Raneem Akel, Jumi A Shin","doi":"10.1080/21541264.2025.2453315","DOIUrl":"https://doi.org/10.1080/21541264.2025.2453315","url":null,"abstract":"Protein engineering has emerged as a powerful approach toward the development of novel therapeutics targeting the MYC/MAX/E-box network, an active driver of >70% of cancers. The MYC/MAX heterodimer regulates numerous genes in our cells by binding the Enhancer box (E-box) DNA site and activating the transcription of downstream genes. Traditional small molecules that inhibit MYC face significant limitations that include toxic effects, drug delivery challenges, and resistance. Recent advances in protein engineering offer promising alternatives by creating protein-based drugs that directly disrupt the MYC/MAX dimerization interface and/or MYC/MAX's binding to specific DNA targets. Designed DNA binding proteins like Omomyc, DuoMyc, ME47, MEF, and Mad inhibit MYC activity through specific dimerization, sequestration, and DNA-binding mechanisms. Compared to small molecules, these engineered proteins can offer superior specificity and efficacy and provide a potential pathway for overcoming the limitations of traditional cancer therapies. The success of these protein therapeutics highlights the importance of protein engineering in developing cancer treatments.","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"1-19"},"PeriodicalIF":3.6,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061100","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}

引用次数: 0

Hypoxia-inducible transcription factors: architects of tumorigenesis and targets for anticancer drug discovery. 缺氧诱导转录因子：肿瘤发生的设计师和抗癌药物发现的目标。

IF 3.6

Transcription-Austin Pub Date : 2024-10-29 DOI: 10.1080/21541264.2024.2417475

Alexander McDermott, Ali Tavassoli

引用次数: 0

Minimization and complete loss of general transcription factor proteins in the intracellular parasite Encephalitozoon cuniculi. 细胞内寄生虫阴沟脑虫体内一般转录因子蛋白的最小化和完全丧失。

IF 3.6

Transcription-Austin Pub Date : 2024-06-01 Epub Date: 2024-05-09 DOI: 10.1080/21541264.2024.2350162

Alana E Belkevich, Andrew Y Khalil, Wayne A Decatur, Ryan J Palumbo, Bruce A Knutson

{"title":"Minimization and complete loss of general transcription factor proteins in the intracellular parasite Encephalitozoon cuniculi.","authors":"Alana E Belkevich, Andrew Y Khalil, Wayne A Decatur, Ryan J Palumbo, Bruce A Knutson","doi":"10.1080/21541264.2024.2350162","DOIUrl":"10.1080/21541264.2024.2350162","url":null,"abstract":"Genome compaction is a common evolutionary feature of parasites. The unicellular, obligate intracellular parasite Encephalitozoon cuniculi has one of smallest known eukaryotic genomes, and is nearly four times smaller than its distant fungi relative, the budding yeast Saccharomyces cerevisiae. 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 E. cuniculi and S. cerevisiae. Surprisingly, our analyses revealed an overall reduction in the size of the proteins comprising transcription machinery of E. cuniculi, 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 E. cuniculi ortholog of Rpc37 (a RNA Polymerase III subunit) more closely resembles the H. sapiens ortholog of Rpc37 than the S. cerevisiae 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.","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"97-113"},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899858","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}

引用次数: 0

Negative feedback systems for modelling NF-κB transcription factor oscillatory activity. 用于模拟 NF-κB 转录因子振荡活动的负反馈系统。

IF 3.6

Transcription-Austin Pub Date : 2024-06-01 Epub Date: 2024-05-13 DOI: 10.1080/21541264.2024.2331887

Bonawentura Kochel

{"title":"Negative feedback systems for modelling NF-κB transcription factor oscillatory activity.","authors":"Bonawentura Kochel","doi":"10.1080/21541264.2024.2331887","DOIUrl":"10.1080/21541264.2024.2331887","url":null,"abstract":"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 3rd- and 4th-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, rela-/- 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.","PeriodicalId":47009,"journal":{"name":"Transcription-Austin","volume":" ","pages":"65-96"},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140913092","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}

引用次数: 0

Deciphering the dynamic code: DNA recognition by transcription factors in the ever-changing genome. 破译动态密码：转录因子在不断变化的基因组中识别 DNA。

IF 3.6

Transcription-Austin Pub Date : 2024-06-01 Epub Date: 2024-07-20 DOI: 10.1080/21541264.2024.2379161

Yumi Minyi Yao, Irina Miodownik, Michael P O'Hagan, Muhammad Jbara, Ariel Afek

引用次数: 0