Cytochrome c prompts the recruitment of its nuclear partners SET/TAF-Iß and NPM1 into biomolecular condensates

Casado-Combreras, Miguel Á. ; Velázquez-Campoy, Adrián (Universidad de Zaragoza) ; Martinho, Marlène ; Belle, Valérie ; De la Rosa, Miguel A. ; Díaz-Moreno, Irene

Resumen: Compartmentalization 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-Iβ plays a key role in both chromatin remodeling and DNA damage response, as does nucleophosmin (NPM1) which indeed participates in nucleolar ribosome synthesis. Whereas phase separation by NPM1 is widely characterized, little is known about that undergone by SET/TAF-Iβ. Here, we show that SET/TAF-Iβ 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-Iβ and NPM1, where two lysine-rich clusters of Cc are essential to recognize molecular surfaces on both partners in a specific and coordinated manner. Cc thus emerges as a small, globular protein with sequence-encoded heterotypic phase-separation properties.

Idioma: Inglés

DOI: 10.1016/j.isci.2024.110435

Año: 2024

Publicado en: ISCIENCE 27, 8 (2024), 110435
ISSN: 2589-0042

Factor impacto JCR: 4.1 (2024)

Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 22 / 135 = 0.163 (2024) - Q1 - T1

Factor impacto CITESCORE: 6.9 - Multidisciplinary (Q1)

Factor impacto SCIMAGO: 1.363 - Multidisciplinary (Q1)

Financiación: info:eu-repo/grantAgreement/ES/MCIU/FPU18-06577
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2021-126663NB-I00

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)