{"title":"Keap1/Nrf2/ARE 信号系统与溶酶体生物发生转录调控因子调控关系的研究","authors":"A. V. Chechushkov, E. B. Menshchikova","doi":"10.1134/s1990519x23060056","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Despite the key role of the Keap1/Nrf2/ARE redox-sensitive signaling system in cell metabolism, almost nothing is known about its association with lysosome biogenesis. In the present work, a theoretical and experimental analysis of the possibility of such a relationship is carried out. By forming a position frequency matrix in the genes of the transcription factors TFEB and TFE3, the presence of a large number of ARE-like sequences in noncoding regions was found. The impact in vitro on J774 cells with activators of the Keap1/Nrf2/ARE system (original synthetic monophenol TS-13 and reference drug <i>tert</i>-butylhydroquinone) leads to dose-dependent induction of <i>Tfe3</i> and <i>Tfeb</i> genes accompanied by a gradual increase in the number of lysosomes and the intensity of the autophagosome–lysosome fusion. Thus, it can be assumed that proteins controlling ARE-dependent genes can influence lysosomal biogenesis.</p>","PeriodicalId":9705,"journal":{"name":"Cell and Tissue Biology","volume":"69 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"An Investigation of the Regulatory Relationship of the Keap1/Nrf2/ARE Signaling System and Transcriptional Regulators of Lysosomal Biogenesis\",\"authors\":\"A. V. Chechushkov, E. B. Menshchikova\",\"doi\":\"10.1134/s1990519x23060056\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3 data-test=\\\"abstract-sub-heading\\\">Abstract</h3><p>Despite the key role of the Keap1/Nrf2/ARE redox-sensitive signaling system in cell metabolism, almost nothing is known about its association with lysosome biogenesis. In the present work, a theoretical and experimental analysis of the possibility of such a relationship is carried out. By forming a position frequency matrix in the genes of the transcription factors TFEB and TFE3, the presence of a large number of ARE-like sequences in noncoding regions was found. The impact in vitro on J774 cells with activators of the Keap1/Nrf2/ARE system (original synthetic monophenol TS-13 and reference drug <i>tert</i>-butylhydroquinone) leads to dose-dependent induction of <i>Tfe3</i> and <i>Tfeb</i> genes accompanied by a gradual increase in the number of lysosomes and the intensity of the autophagosome–lysosome fusion. Thus, it can be assumed that proteins controlling ARE-dependent genes can influence lysosomal biogenesis.</p>\",\"PeriodicalId\":9705,\"journal\":{\"name\":\"Cell and Tissue Biology\",\"volume\":\"69 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-12-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell and Tissue Biology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1134/s1990519x23060056\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"Biochemistry, Genetics and Molecular Biology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell and Tissue Biology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1134/s1990519x23060056","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
引用次数: 0
摘要
摘要尽管Keap1/Nrf2/ARE氧化还原敏感信号系统在细胞新陈代谢中起着关键作用，但人们对它与溶酶体生物发生的关系几乎一无所知。本研究对这种关系的可能性进行了理论和实验分析。通过在转录因子 TFEB 和 TFE3 的基因中形成位置频率矩阵，发现在非编码区存在大量类似 ARE 的序列。Keap1/Nrf2/ARE 系统激活剂（原始合成单酚 TS-13 和参考药物叔丁基对苯二酚）对 J774 细胞的体外影响导致 Tfe3 和 Tfeb 基因的剂量依赖性诱导，同时溶酶体数量和自噬体-溶酶体融合强度逐渐增加。因此，可以认为控制 ARE 依赖性基因的蛋白质可以影响溶酶体的生物发生。
An Investigation of the Regulatory Relationship of the Keap1/Nrf2/ARE Signaling System and Transcriptional Regulators of Lysosomal Biogenesis
Abstract
Despite the key role of the Keap1/Nrf2/ARE redox-sensitive signaling system in cell metabolism, almost nothing is known about its association with lysosome biogenesis. In the present work, a theoretical and experimental analysis of the possibility of such a relationship is carried out. By forming a position frequency matrix in the genes of the transcription factors TFEB and TFE3, the presence of a large number of ARE-like sequences in noncoding regions was found. The impact in vitro on J774 cells with activators of the Keap1/Nrf2/ARE system (original synthetic monophenol TS-13 and reference drug tert-butylhydroquinone) leads to dose-dependent induction of Tfe3 and Tfeb genes accompanied by a gradual increase in the number of lysosomes and the intensity of the autophagosome–lysosome fusion. Thus, it can be assumed that proteins controlling ARE-dependent genes can influence lysosomal biogenesis.
期刊介绍：
The journal publishes papers on vast aspects of cell research, including morphology, biochemistry, biophysics, genetics, molecular biology, immunology. The journal accepts original experimental studies, theoretical articles suggesting novel principles and approaches, presentations of new hypotheses, reviews highlighting major developments in cell biology, discussions. The main objective of the journal is to provide a competent representation and integration of research made on cells (animal and plant cells, both in vivo and in cell culture) offering insight into the structure and functions of live cells as a whole. Characteristically, the journal publishes articles on biology of free-living and parasitic protists, which, unlike Metazoa, are eukaryotic organisms at the cellular level of organization.
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