Bradbury Lobato, Melissa, 1983-Borràs, EvaCastellví, JosepMéndez, OlgaSánchez-Iglesias, José LuisPérez-Benavente, AssumpcióGil-Moreno, AntonioSabidó Aguadé, Eduard, 1981-Santamaria, Anna2022-06-012022-06-012022Bradbury M, Borràs E, Castellví J, Méndez O, Sánchez-Iglesias, JL et al. BRCA1 mutations in high-grade serous ovarian cancer are associated with proteomic changes in DNA repair, splicing, transcription regulation and signaling. Sci Rep. 2022 Mar 15;12(1):4445. DOI:10.1038/s41598-022-08461-02045-2322http://hdl.handle.net/10230/53343Despite recent advances in the management of BRCA1 mutated high-grade serous ovarian cancer (HGSC), the physiology of these tumors remains poorly understood. Here we provide a comprehensive molecular understanding of the signaling processes that drive HGSC pathogenesis with the addition of valuable ubiquitination profiling, and their dependency on BRCA1 mutation-state directly in patient-derived tissues. Using a multilayered proteomic approach, we show the tight coordination between the ubiquitination and phosphorylation regulatory layers and their role in key cellular processes related to BRCA1-dependent HGSC pathogenesis. In addition, we identify key bridging proteins, kinase activity, and post-translational modifications responsible for molding distinct cancer phenotypes, thus providing new opportunities for therapeutic intervention, and ultimately advance towards a more personalized patient care.application/pdfeng© Melissa Bradbury et al 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were madeOvaris -- CàncerGenòmicaGenèticainfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41598-022-08461-0info:eu-repo/semantics/openAccess