{"doi":"10.1016/j.celrep.2025.115274","title":"Wnt signaling inhibits casein kinase 1α activity by modulating its interaction with protein phosphatase 2A","abstract":"The mechanism by which Wnt signaling, an essential pathway controlling development and disease, stabilizes β-catenin has been a subject of debate over the last four decades. Casein kinase 1α (CK1α) functions as a pivotal negative regulator of this signaling pathway, initiating the events that destabilize β-catenin. However, whether and how CK1α activity is regulated in Wnt-off and Wnt-on states remains poorly understood. We now show that CK1α activity requires its association with the α catalytic subunit of protein phosphatase 2A (PPP2CA) on AXIN, the scaffold protein of the β-catenin destruction complex. Wnt stimulation induces the dissociation of PPP2CA from CK1α, resulting in CK1α autophosphorylation and its consequent inactivation. Moreover, autophosphorylated CK1α is enriched in a subset of colorectal cancers (CRCs) harboring constitutive Wnt activation. Our findings identify a mechanism by which Wnt stimulation inactivates CK1α, filling a critical gap in our understanding of Wnt signaling, with relevance for CRC.","journal":"Cell Reports","year":2025,"id":530366,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":736295,"name":"Wenhui Lu","orcid":"0009-0002-2674-4254","position":1,"is_corresponding":false},{"id":1319529,"name":"Siva Bharath Merugu","orcid":"0000-0003-1750-3256","position":2,"is_corresponding":false},{"id":1410433,"name":"Aradhana Bharti","orcid":null,"position":3,"is_corresponding":false},{"id":1129398,"name":"Said M. Afify","orcid":"0000-0003-4026-1400","position":4,"is_corresponding":false},{"id":1410434,"name":"Lauren Schnitkey","orcid":null,"position":5,"is_corresponding":false},{"id":494496,"name":"Daniel T. Wynn","orcid":"0000-0001-7447-4346","position":6,"is_corresponding":false},{"id":594938,"name":"Fan Yang","orcid":"0000-0003-3730-8503","position":7,"is_corresponding":false},{"id":269145,"name":"Thomas Rohwetter","orcid":null,"position":8,"is_corresponding":false},{"id":494495,"name":"Anmada Nayak","orcid":"0000-0003-1275-0899","position":9,"is_corresponding":false},{"id":405058,"name":"Nawat Bunnag","orcid":"0000-0002-2594-0459","position":10,"is_corresponding":false},{"id":458651,"name":"Carolina Cywiak","orcid":"0000-0002-5716-0051","position":11,"is_corresponding":false},{"id":258003,"name":"Hsin‐Yao Tang","orcid":"0000-0003-1838-018X","position":12,"is_corresponding":false},{"id":55228,"name":"Brent T. Harris","orcid":"0000-0002-9746-4906","position":13,"is_corresponding":false},{"id":496761,"name":"Christopher Albanese","orcid":null,"position":14,"is_corresponding":false},{"id":1320509,"name":"Chukwuemeka Ihemelandu","orcid":null,"position":15,"is_corresponding":false},{"id":445763,"name":"Melanie H. Cobb","orcid":"0000-0003-0833-5473","position":16,"is_corresponding":false},{"id":273955,"name":"Arminja N. Kettenbach","orcid":"0000-0003-3979-4576","position":17,"is_corresponding":false},{"id":241280,"name":"Ethan Lee","orcid":"0000-0001-8405-6156","position":18,"is_corresponding":false},{"id":266302,"name":"Yashi Ahmed","orcid":"0000-0002-7472-6010","position":19,"is_corresponding":false},{"id":266301,"name":"David J. Robbins","orcid":"0000-0003-0190-2973","position":20,"is_corresponding":false},{"id":494494,"name":"Chen Shen","orcid":"0000-0002-7119-8443","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T02:51:05.836974Z","pmid":"39908140","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,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}