{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Xu F"],"funding":["National Natural Science Foundation of China (National Science Foundation of China)"],"pagination":["716"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12504418"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(1)"],"pubmed_abstract":["The Casitas B-lineage lymphoma (Cbl) family proteins are E3 ubiquitin ligases implicated in the regulation of various immune cells. However, their function in macrophages remains unclear. Here, we identify both Cbl-b and c-Cbl (Cbls) as inhibitors of macrophage proliferation and promoters of macrophage apoptosis. Mechanically, we identify that Cbls functions upstream of AKT and Erk to mediate the ubiquitination and degradation of M-CSFR. M-CSF stimulation promotes dimerization and autophosphorylation activation of M-CSFR on the macrophage membrane, thereby activating downstream PI3K-AKT and Erk signaling pathways, leading to different biological effects such as macrophage proliferation and survival. At the same time, the Y559 site of the M-CSFR undergoes autophosphorylation, which can prom"],"journal":["Cell death & disease"],"pubmed_title":["E3 Ubiquitin ligases Cbl-b and c-Cbl maintain the homeostasis of macrophages by regulating the M-CSF/M-CSFR signaling axis."],"pmcid":["PMC12504418"],"funding_grant_id":["82370020","81771667","82070009","82170012","82071765","81970027","82270018"],"pubmed_authors":["Qiao G","Wu M","Li J","Zhang J","Cai J","Tan C","Xu F","Xia T","Shi Y","Tang K","Li X","Zhu P","Yang Y","Shao Y","Chen Z","Wang W","Gao X","Wang Y","Xu X","Huang B","Hao C","Zhou J"],"additional_accession":[]},"is_claimable":false,"name":"E3 Ubiquitin ligases Cbl-b and c-Cbl maintain the homeostasis of macrophages by regulating the M-CSF/M-CSFR signaling axis.","description":"The Casitas B-lineage lymphoma (Cbl) family proteins are E3 ubiquitin ligases implicated in the regulation of various immune cells. However, their function in macrophages remains unclear. Here, we identify both Cbl-b and c-Cbl (Cbls) as inhibitors of macrophage proliferation and promoters of macrophage apoptosis. Mechanically, we identify that Cbls functions upstream of AKT and Erk to mediate the ubiquitination and degradation of M-CSFR. M-CSF stimulation promotes dimerization and autophosphorylation activation of M-CSFR on the macrophage membrane, thereby activating downstream PI3K-AKT and Erk signaling pathways, leading to different biological effects such as macrophage proliferation and survival. At the same time, the Y559 site of the M-CSFR undergoes autophosphorylation, which can prom","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Oct","modification":"2026-06-04T06:28:19.141Z","creation":"2026-05-06T03:13:22.78Z"},"accession":"S-EPMC12504418","cross_references":{"pubmed":["41057360"],"doi":["10.1038/s41419-025-08047-4"]}}