biostudies-literatureKonig SMISCRA CINECACarlsbergfondetDanmarks GrundforskningsfondLEO FoundationNovo Nordisk Foundation Center for Protein ResearchPartnership for Advanced Computing in Europe AISBLLEO Fondete1007485https://www.ebi.ac.uk/biostudies/studies/S-EPMC6927658biostudies-literatureUnknown15(12)Apoptosis is an essential defensive mechanism against tumorigenesis. Proteins of the B-cell lymphoma-2 (Bcl-2) family regulate programmed cell death by the mitochondrial apoptosis pathway. In response to intracellular stress, the apoptotic balance is governed by interactions of three distinct subgroups of proteins; the activator/sensitizer BH3 (Bcl-2 homology 3)-only proteins, the pro-survival, and the pro-apoptotic executioner proteins. Changes in expression levels, stability, and functional impairment of pro-survival proteins can lead to an imbalance in tissue homeostasis. Their overexpression or hyperactivation can result in oncogenic effects. Pro-survival Bcl-2 family members carry out their function by binding the BH3 short linear motif of pro-apoptotic proteins in a modular way, creaPLoS computational biologyAlterations of the interactome of Bcl-2 proteins in breast cancer at the transcriptional, mutational and structural level.PMC6927658DNRF125PI Søren BrunakCF18-0314P10C8YXRKHP10CBLBWODECI-15thDECI-14thLF17006Lambrughi MKonig SMRissler VTerkelsen TPapaleo EfalseAlterations of the interactome of Bcl-2 proteins in breast cancer at the transcriptional, mutational and structural level.Apoptosis is an essential defensive mechanism against tumorigenesis. Proteins of the B-cell lymphoma-2 (Bcl-2) family regulate programmed cell death by the mitochondrial apoptosis pathway. In response to intracellular stress, the apoptotic balance is governed by interactions of three distinct subgroups of proteins; the activator/sensitizer BH3 (Bcl-2 homology 3)-only proteins, the pro-survival, and the pro-apoptotic executioner proteins. Changes in expression levels, stability, and functional impairment of pro-survival proteins can lead to an imbalance in tissue homeostasis. Their overexpression or hyperactivation can result in oncogenic effects. Pro-survival Bcl-2 family members carry out their function by binding the BH3 short linear motif of pro-apoptotic proteins in a modular way, crea2019-01-01T00:00:00Z2019 Dec2026-05-04T09:23:03.153Z2020-05-22T07:18:01ZS-EPMC69276583182596910.1371/journal.pcbi.1007485