{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Edelmann J"],"funding":["Cancer Research UK","Barts Charity","NCI NIH HHS"],"pagination":["102089"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7878992"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["24(2)"],"pubmed_abstract":["The anti-CD20 monoclonal antibodies rituximab and obinutuzumab differ in their mechanisms of action, with obinutuzumab evoking greater direct B cell death. To characterize the signaling processes responsible for improved B cell killing by obinutuzumab, we undertook a phosphoproteomics approach and demonstrate that rituximab and obinutuzumab differentially activate pathways downstream of the B cell receptor. Although both antibodies induce strong ERK and MYC activation sufficient to promote cell-cycle arrest and B cell death, obinutuzumab exceeds rituximab in supporting apoptosis induction by means of aberrant SYK phosphorylation. In contrast, rituximab elicits stronger anti-apoptotic signals by activating AKT, by impairing pro-apoptotic BAD, and by releasing membrane-bound NOTCH1 to up-reg"],"journal":["iScience"],"pubmed_title":["Rituximab and obinutuzumab differentially hijack the B cell receptor and NOTCH1 signaling pathways."],"pmcid":["PMC7878992"],"funding_grant_id":["P01 CA081534","MRD0203","24721"],"pubmed_authors":["Holzmann K","Klymenko T","Gribben JG","Cutillas P","Dokal AD","Braun A","Vilventhraraja E","Edelmann J","Britton D","Cragg M","Dohner H"],"additional_accession":[]},"is_claimable":false,"name":"Rituximab and obinutuzumab differentially hijack the B cell receptor and NOTCH1 signaling pathways.","description":"The anti-CD20 monoclonal antibodies rituximab and obinutuzumab differ in their mechanisms of action, with obinutuzumab evoking greater direct B cell death. To characterize the signaling processes responsible for improved B cell killing by obinutuzumab, we undertook a phosphoproteomics approach and demonstrate that rituximab and obinutuzumab differentially activate pathways downstream of the B cell receptor. Although both antibodies induce strong ERK and MYC activation sufficient to promote cell-cycle arrest and B cell death, obinutuzumab exceeds rituximab in supporting apoptosis induction by means of aberrant SYK phosphorylation. In contrast, rituximab elicits stronger anti-apoptotic signals by activating AKT, by impairing pro-apoptotic BAD, and by releasing membrane-bound NOTCH1 to up-reg","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Feb","modification":"2026-05-01T11:23:48.135Z","creation":"2021-02-21T11:42:00Z"},"accession":"S-EPMC7878992","cross_references":{"pubmed":["33615197"],"doi":["10.1016/j.isci.2021.102089"]}}