{"doi":"10.1158/0008-5472.can-05-2474","title":"MUC1 Oncoprotein Blocks Glycogen Synthase Kinase 3β–Mediated Phosphorylation and Degradation of β-Catenin","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Dysregulation of β-catenin is of importance to the development of diverse human malignancies. The MUC1 oncoprotein is aberrantly overexpressed by most human carcinomas and associates with β-catenin. However, the functional significance of the MUC1-β-catenin interaction is not known. Here, we show that MUC1 increases β-catenin levels in the cytoplasm and nucleus of carcinoma cells. Previous studies have shown that glycogen synthase kinase 3β (GSK3β) phosphorylates β-catenin and thereby targets it for proteosomal degradation. Consistent with the up-regulation of β-catenin levels, our results show that MUC1 blocks GSK3β-mediated phosphorylation and degradation of β-catenin. To further define the interaction between MUC1 and β-catenin, we identified a serine-rich motif (SRM) in the MUC1 cytoplasmic domain that binds directly to β-catenin Armadillo repeats. Mutation of the SRM attenuated binding of MUC1 to β-catenin and MUC1-mediated inhibition of β-catenin degradation. Importantly, disruption of the MUC1-β-catenin interaction with the SRM mutant also attenuated MUC1-induced anchorage-dependent and -independent growth and delayed MUC1-mediated tumorigenicity. These findings indicate that MUC1 promotes transformation, at least in part, by blocking GSK3β-mediated phosphorylation and thereby degradation of β-catenin.</jats:p>","journal":"Cancer Research","year":2005,"id":21379,"datarank":8.044739951319738,"base_score":5.438079308923196,"endowment":5.438079308923196,"self_citation_contribution":0.8157118963384794,"citation_network_contribution":7.229028054981258,"self_endowment_contribution":0.8157118963384794,"citer_contribution":7.229028054981258,"corpus_percentile":null,"corpus_rank":null,"citation_count":229,"citer_count":156,"citers_with_citation_signal":140,"citers_with_endowment":140,"datacite_reuse_total":2,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":137859,"name":"Dongshu Chen","orcid":null,"position":1,"is_corresponding":false},{"id":28944,"name":"Derek Liu","orcid":"0000-0001-5744-1147","position":2,"is_corresponding":false},{"id":137860,"name":"Li Yin","orcid":null,"position":3,"is_corresponding":false},{"id":137861,"name":"Surender Kharbanda","orcid":null,"position":4,"is_corresponding":false},{"id":137862,"name":"Donald Kufe","orcid":null,"position":5,"is_corresponding":false},{"id":2467,"name":"Lei Huang","orcid":"0000-0002-3490-3393","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":5.438079308923196,"endowment":5.438079308923196,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"16288032","pmcid":null,"openalex_id":"https://openalex.org/W2034102636","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"CA29431","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA97098","title":null}],"total_grants":2,"fwci":4.5484,"citation_percentile":0.95322366,"influential_citations":5,"citation_trend":[{"year":2012,"count":14},{"year":2013,"count":12},{"year":2014,"count":13},{"year":2015,"count":15},{"year":2016,"count":19},{"year":2017,"count":12},{"year":2018,"count":5},{"year":2019,"count":6},{"year":2020,"count":8},{"year":2021,"count":9},{"year":2022,"count":11},{"year":2023,"count":5},{"year":2024,"count":3},{"year":2025,"count":9},{"year":2026,"count":2}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://aacrjournals.org/cancerres/article-pdf/65/22/10413/2537730/10413-10422.pdf","host_type":"journal"},{"url":"https://aacrjournals.org/cancerres/article-pdf/65/22/10413/2537730/10413-10422.pdf","host_type":"BRONZE"},{"url":"https://aacrjournals.org/cancerres/article-pdf/65/22/10413/2537730/10413-10422.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1158/0008-5472.can-05-2474","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/16288032","host_type":"repository"}],"fields_of_study":["Wnt/β-catenin signaling in development and cancer","Cancer-related gene regulation","Kruppel-like factors research","Biology","Medicine","Amino Acid Motifs","Cytoplasm","Glycogen Synthase Kinase 3","Glycogen Synthase Kinase 3 beta","HeLa Cells","Humans","Mucin-1","Phosphorylation","Protein Structure, Tertiary","RNA, Small Interfering","Transfection","Up-Regulation","beta Catenin"],"mesh_terms":["Glycogen Synthase Kinase 3 beta","Cytoplasm","HeLa Cells","Humans","Phosphorylation","Transfection","Up-Regulation","Protein Structure, Tertiary","Mucin-1","Amino Acid Motifs","RNA, Small Interfering","Glycogen Synthase Kinase 3","beta Catenin","Hela Cells"],"keywords":["GSK-3","GSK3B","Beta-catenin","Phosphorylation","Catenin","Glycogen synthase","Biology","MUC1","Cell biology","Serine","Cancer research","Chemistry","Molecular biology","Wnt signaling pathway","Signal transduction","Biochemistry"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.19768046","title":"Additional file 1 of Beta 2 adrenergic receptor and mu opioid receptor interact to potentiate the aggressiveness of human breast cancer cell by activating the glycogen synthase kinase 3 signaling","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.19768046.v1","title":"Additional file 1 of Beta 2 adrenergic receptor and mu opioid receptor interact to potentiate the aggressiveness of human breast cancer cell by activating the glycogen synthase kinase 3 signaling","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-06T15:43:08.378565Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}