{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Li Y"],"funding":["NCI NIH HHS","NIGMS NIH HHS"],"pagination":["2360-2371"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8832461"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["138(23)"],"pubmed_abstract":["B-cell-activating factor (BAFF) mediates B-cell survival and, when deregulated, contributes to autoimmune diseases and B-cell malignancies. The mechanism connecting BAFF receptor (BAFFR) signal to downstream pathways and pathophysiological functions is not well understood. Here we identified DYRK1a as a kinase that responds to BAFF stimulation and mediates BAFF-induced B-cell survival. B-cell-specific DYRK1a deficiency causes peripheral B-cell reduction and ameliorates autoimmunity in a mouse model of lupus. An unbiased screen identified DYRK1a as a protein that interacts with TRAF3, a ubiquitin ligase component mediating degradation of the noncanonical nuclear factor (NF)-κB-inducing kinase (NIK). DYRK1a phosphorylates TRAF3 at serine-29 to interfere with its function in mediating NIK degradation, thereby facilitating BAFF-induced NIK accumulation and noncanonical NF-κB activation. Interestingly, B-cell acute lymphoblastic leukemia (B-ALL) cells express high levels of BAFFR and respond to BAFF for noncanonical NF-κB activation and survival in a DYRK1a-dependent manner. Furthermore, DYRK1a promotes a mouse model of B-ALL through activation of the noncanonical NF-κB pathway. These results establish DYRK1a as a critical BAFFR signaling mediator and provide novel insight into B-ALL pathogenesis."],"journal":["Blood"],"pubmed_title":["DYRK1a mediates BAFF-induced noncanonical NF-κB activation to promote autoimmunity and B-cell leukemogenesis."],"pmcid":["PMC8832461"],"funding_grant_id":["R01 GM084459","P30 CA016672","P30 CA125123"],"pubmed_authors":["Yang JY","Sun SC","Jie Z","Konopleva MY","Xie X","Cheng X","Ko CJ","Li Y","Jain A","Jung SY","Zhu L","Baran N","Gao T"],"additional_accession":[]},"is_claimable":false,"name":"DYRK1a mediates BAFF-induced noncanonical NF-κB activation to promote autoimmunity and B-cell leukemogenesis.","description":"B-cell-activating factor (BAFF) mediates B-cell survival and, when deregulated, contributes to autoimmune diseases and B-cell malignancies. The mechanism connecting BAFF receptor (BAFFR) signal to downstream pathways and pathophysiological functions is not well understood. Here we identified DYRK1a as a kinase that responds to BAFF stimulation and mediates BAFF-induced B-cell survival. B-cell-specific DYRK1a deficiency causes peripheral B-cell reduction and ameliorates autoimmunity in a mouse model of lupus. An unbiased screen identified DYRK1a as a protein that interacts with TRAF3, a ubiquitin ligase component mediating degradation of the noncanonical nuclear factor (NF)-κB-inducing kinase (NIK). DYRK1a phosphorylates TRAF3 at serine-29 to interfere with its function in mediating NIK degradation, thereby facilitating BAFF-induced NIK accumulation and noncanonical NF-κB activation. Interestingly, B-cell acute lymphoblastic leukemia (B-ALL) cells express high levels of BAFFR and respond to BAFF for noncanonical NF-κB activation and survival in a DYRK1a-dependent manner. Furthermore, DYRK1a promotes a mouse model of B-ALL through activation of the noncanonical NF-κB pathway. These results establish DYRK1a as a critical BAFFR signaling mediator and provide novel insight into B-ALL pathogenesis.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Dec","modification":"2025-04-18T20:03:52.519Z","creation":"2025-04-07T07:50:20.263Z"},"accession":"S-EPMC8832461","cross_references":{"pubmed":["34255829"],"doi":["10.1182/blood.2021011247"]}}