Ildikó Kristó, Zoltán Kovács, Anikó Szabó, Péter Borkúti, Alexandra Gráf, Ádám Tamás Sánta, Aladár Pettkó-Szandtner, Edit Ábrahám, Viktor Honti, Zoltán Lipinszki, Péter Vilmos
{"title":"Moesin 通过与细胞核中 Mediator 复合物的 Med15 亚基直接结合,促进热休克基因的反应。","authors":"Ildikó Kristó, Zoltán Kovács, Anikó Szabó, Péter Borkúti, Alexandra Gráf, Ádám Tamás Sánta, Aladár Pettkó-Szandtner, Edit Ábrahám, Viktor Honti, Zoltán Lipinszki, Péter Vilmos","doi":"10.1098/rsob.240110","DOIUrl":null,"url":null,"abstract":"<p><p>The members of the evolutionary conserved actin-binding Ezrin, Radixin and Moesin (ERM) protein family are involved in numerous key cellular processes in the cytoplasm. In the last decades, ERM proteins, like actin and other cytoskeletal components, have also been shown to be functional components of the nucleus; however, the molecular mechanism behind their nuclear activities remained unclear. Therefore, our primary aim was to identify the nuclear protein interactome of the single <i>Drosophila</i> ERM protein, Moesin. We demonstrate that Moesin directly interacts with the Mediator complex through direct binding to its Med15 subunit, and the presence of Moesin at the regulatory regions of the <i>Hsp70Ab</i> heat shock gene was found to be Med15-dependent. Both Moesin and Med15 bind to heat shock factor (Hsf), and they are required for proper <i>Hsp</i> gene expression under physiological conditions. Moreover, we confirmed that Moesin, Med15 and Hsf are able to bind the monomeric form of actin and together they form a complex in the nucleus. These results elucidate a mechanism by which ERMs function within the nucleus. Finally, we present the direct interaction of the human orthologues of <i>Drosophila</i> Moesin and Med15, which highlights the evolutionary significance of our finding.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":"14 10","pages":"240110"},"PeriodicalIF":4.5000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444770/pdf/","citationCount":"0","resultStr":"{\"title\":\"Moesin contributes to heat shock gene response through direct binding to the Med15 subunit of the Mediator complex in the nucleus.\",\"authors\":\"Ildikó Kristó, Zoltán Kovács, Anikó Szabó, Péter Borkúti, Alexandra Gráf, Ádám Tamás Sánta, Aladár Pettkó-Szandtner, Edit Ábrahám, Viktor Honti, Zoltán Lipinszki, Péter Vilmos\",\"doi\":\"10.1098/rsob.240110\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The members of the evolutionary conserved actin-binding Ezrin, Radixin and Moesin (ERM) protein family are involved in numerous key cellular processes in the cytoplasm. In the last decades, ERM proteins, like actin and other cytoskeletal components, have also been shown to be functional components of the nucleus; however, the molecular mechanism behind their nuclear activities remained unclear. Therefore, our primary aim was to identify the nuclear protein interactome of the single <i>Drosophila</i> ERM protein, Moesin. We demonstrate that Moesin directly interacts with the Mediator complex through direct binding to its Med15 subunit, and the presence of Moesin at the regulatory regions of the <i>Hsp70Ab</i> heat shock gene was found to be Med15-dependent. Both Moesin and Med15 bind to heat shock factor (Hsf), and they are required for proper <i>Hsp</i> gene expression under physiological conditions. Moreover, we confirmed that Moesin, Med15 and Hsf are able to bind the monomeric form of actin and together they form a complex in the nucleus. These results elucidate a mechanism by which ERMs function within the nucleus. Finally, we present the direct interaction of the human orthologues of <i>Drosophila</i> Moesin and Med15, which highlights the evolutionary significance of our finding.</p>\",\"PeriodicalId\":19629,\"journal\":{\"name\":\"Open Biology\",\"volume\":\"14 10\",\"pages\":\"240110\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444770/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Open Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1098/rsob.240110\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/2 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Open Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1098/rsob.240110","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/2 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Moesin contributes to heat shock gene response through direct binding to the Med15 subunit of the Mediator complex in the nucleus.
The members of the evolutionary conserved actin-binding Ezrin, Radixin and Moesin (ERM) protein family are involved in numerous key cellular processes in the cytoplasm. In the last decades, ERM proteins, like actin and other cytoskeletal components, have also been shown to be functional components of the nucleus; however, the molecular mechanism behind their nuclear activities remained unclear. Therefore, our primary aim was to identify the nuclear protein interactome of the single Drosophila ERM protein, Moesin. We demonstrate that Moesin directly interacts with the Mediator complex through direct binding to its Med15 subunit, and the presence of Moesin at the regulatory regions of the Hsp70Ab heat shock gene was found to be Med15-dependent. Both Moesin and Med15 bind to heat shock factor (Hsf), and they are required for proper Hsp gene expression under physiological conditions. Moreover, we confirmed that Moesin, Med15 and Hsf are able to bind the monomeric form of actin and together they form a complex in the nucleus. These results elucidate a mechanism by which ERMs function within the nucleus. Finally, we present the direct interaction of the human orthologues of Drosophila Moesin and Med15, which highlights the evolutionary significance of our finding.
期刊介绍:
Open Biology is an online journal that welcomes original, high impact research in cell and developmental biology, molecular and structural biology, biochemistry, neuroscience, immunology, microbiology and genetics.