2025-03-242025-03-242024-07-02Casado Combreras, M.Á., Velázquez Campoy, A., Martinho, M., Belle, V., Rosa Acosta, M.Á.d.l. y Díaz Moreno, I. (2024). Cytochrome c prompts the recruitment of its nuclear partners SET/TAF-Iβ and NPM1 into biomolecular condensates. iScience, 27 (8), 110435. https://doi.org/10.1016/j.isci.2024.110435.2589-0042https://hdl.handle.net/11441/170763Compartmentalization of proteins by liquid-liquid phase separation (LLPS) is used by cells to control biochemical reactions spatially and temporally. Among them, the recruitment of proteins to DNA foci and nucleolar trafficking occur by biomolecular condensation. Within this frame, the oncoprotein SET/ TAF-Ib plays a keyrole in bothchromatin remodelingandDNAdamageresponse,asdoesnucleophosmin (NPM1)whichindeedparticipatesinnucleolar ribosome synthesis. Whereasphase separation byNPM1is widelycharacterized,little is known aboutthatundergonebySET/TAF-Ib.Here,weshowthatSET/TAF-Ib experiences phase separation together with respiratory cytochrome c (Cc), which translocates to the nucleus upon DNA damage. Here we report the molecular mechanisms governing Cc-induced phase separation of SET/TAF-IbandNPM1,wheretwolysine-richclustersofCcareessentialtorecognizemolecular surfaces on both partners in a specific and coordinated manner. Cc thus emerges as a small, globular protein with sequence-encoded heterotypic phase-separation propertiesapplication/pdf25 p.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccess10.1016/j.isci.2024.110435