Moesin contributes to heat shock gene response through direct binding to the Med15 subunit of the Mediator complex in the nucleus

Kristó, Ildikó and Kovács, Zoltán and Szabó, Anikó and Borkúti, Péter and Gráf, Alexandra and Sánta, Ádám Tamás and Pettkó-Szandtner, Aladár and Ábrahám, Edit and Honti, Viktor and Lipinszki, Zoltán and Vilmos, Péter (2024) Moesin contributes to heat shock gene response through direct binding to the Med15 subunit of the Mediator complex in the nucleus. OPEN BIOLOGY, 14 (10). No.240110. ISSN 2046-2441

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Abstract

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.

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