Identification of High-Efficiency β-Catenin Protein Degradation As Critical Vulnerability in B-Cell Malignancies
Cosgun K, Robinson M, Agadzhanian N, Cheng Z, Oulghazi S, Berning P, Fonseca-Arce D, Kume K, Fontaine J, Chan L, Lee J, Yu F, Qian Z, Song J, Chan W, Chen J, Taketo M, Schjerven H, Müschen M. Identification of High-Efficiency β-Catenin Protein Degradation As Critical Vulnerability in B-Cell Malignancies. Blood 2024, 144: 4125-4125. DOI: 10.1182/blood-2024-208125.Peer-Reviewed Original ResearchProtein degradation pathwaysB-ALL cellsProtein degradationRepression of MYCTranscriptional activity of MYCCell deathAcute cell deathLoss of colony formationChIP-seq analysisActive enhancer marksB-cell malignanciesSuper-enhancer regionsActivation of MYCIkaros transcription factorB-lymphoid cellsCell linesB cell identityDefective protein degradationB-cateninNon-lymphoid cell linesDegradation pathwayMantle cell lymphomaProtein levelsB-ALLChIP-seqTargeting β-Catenin Protein Degradation in Refractory B-Cell Malignancies
Cosgun K, Robinson M, Agadzhanian N, Berning P, Fonseca-Arce D, Leveille E, Kothari S, Davids M, Jellusova J, Müschen M. Targeting β-Catenin Protein Degradation in Refractory B-Cell Malignancies. Blood 2024, 144: 1412. DOI: 10.1182/blood-2024-208598.Peer-Reviewed Original ResearchProtein degradationRepression of MYCTranscriptional repression of MYCTranscriptional repressionPromote survivalProteasome inhibitorsProtein degradation pathwaysCell typesN-terminal residuesInduce cell deathRefractory B-cell malignanciesB-cateninB-cell malignanciesRNAi screenInteractome studiesB cell selectionRepressive complexesGene dependenciesProteasomal degradationB cellsChemogenomic screensProteasome inhibitor bortezomibActivated mycDeletion of Ctnnb1Cell death