Proteomics

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BRCA1-dependent ubiquitination and phosphorylation regulates signaling events in high-grade serous ovarian cancer tissues


ABSTRACT: Despite 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 and their dependency on BRCA1 mutation-state directly in patient-derived tissues. Using a multi-layered 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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Ovary

DISEASE(S): Malignant Neoplasm Of Ovary

SUBMITTER: Melissa Bradbury  

LAB HEAD: Eduard Sabidó

PROVIDER: PXD020271 | Pride | 2022-04-04

REPOSITORIES: Pride

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Publications

BRCA1 mutations in high-grade serous ovarian cancer are associated with proteomic changes in DNA repair, splicing, transcription regulation and signaling.

Bradbury Melissa M   Borràs Eva E   Castellví Josep J   Méndez Olga O   Sánchez-Iglesias José Luis JL   Pérez-Benavente Assumpció A   Gil-Moreno Antonio A   Sabidó Eduard E   Santamaria Anna A  

Scientific reports 20220315 1


Despite 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 ubiquiti  ...[more]

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