{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lin H"],"funding":["National Natural Science Foundation of China","National Natural Science Foundation of China (National Science Foundation of China)"],"pagination":["2648-2659"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8632971"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["18(12)"],"pubmed_abstract":["The IL-6-STAT3 axis is critically involved in inflammation-associated carcinogenesis (IAC). How this axis is regulated to modulate IAC remains unknown. Here, we show that the plasma membrane-associated E3 ubiquitin ligase MARCH3 negatively regulates STAT3 activation triggered by IL-6, as well as another IL-6 subfamily member, Oncostatin M (OSM). MARCH3 is associated with the IL-6 receptor α-chain (IL-6Rα) and its coreceptor gp130. Biochemical experiments indicated that MARCH3 mediates the polyubiquitination of IL-6Rα at K401 and gp130 at K849 following IL-6 stimulation, leading to their translocation to and degradation in lysosomes. MARCH3 deficiency increases IL-6- and OSM-triggered activation of STAT3 and induction of downstream effector genes in various cell types. MARCH3 deficiency enh"],"journal":["Cellular & molecular immunology"],"pubmed_title":["The membrane-associated E3 ubiquitin ligase MARCH3 downregulates the IL-6 receptor and suppresses colitis-associated carcinogenesis."],"pmcid":["PMC8632971"],"funding_grant_id":["31830024"],"pubmed_authors":["Zeng LW","Feng L","Cui KS","Li S","Zhang LX","Sun YH","Lin H","Xu WH","Shu HB","Gao D"],"additional_accession":[]},"is_claimable":false,"name":"The membrane-associated E3 ubiquitin ligase MARCH3 downregulates the IL-6 receptor and suppresses colitis-associated carcinogenesis.","description":"The IL-6-STAT3 axis is critically involved in inflammation-associated carcinogenesis (IAC). How this axis is regulated to modulate IAC remains unknown. Here, we show that the plasma membrane-associated E3 ubiquitin ligase MARCH3 negatively regulates STAT3 activation triggered by IL-6, as well as another IL-6 subfamily member, Oncostatin M (OSM). MARCH3 is associated with the IL-6 receptor α-chain (IL-6Rα) and its coreceptor gp130. Biochemical experiments indicated that MARCH3 mediates the polyubiquitination of IL-6Rα at K401 and gp130 at K849 following IL-6 stimulation, leading to their translocation to and degradation in lysosomes. MARCH3 deficiency increases IL-6- and OSM-triggered activation of STAT3 and induction of downstream effector genes in various cell types. MARCH3 deficiency enh","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Dec","modification":"2025-04-25T20:50:59.866Z","creation":"2025-04-06T08:33:41.591Z"},"accession":"S-EPMC8632971","cross_references":{"pubmed":["34785732"],"doi":["10.1038/s41423-021-00799-1"]}}