{"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}
引用次数: 0
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.