{"doi":"10.1016/j.celrep.2020.108140","title":"The GSK-3β-FBXL21 Axis Contributes to Circadian TCAP Degradation and Skeletal Muscle Function","abstract":"FBXL21 is a clock-controlled E3 ligase modulating circadian periodicity via subcellular-specific CRYPTOCHROME degradation. How FBXL21 regulates tissue-specific circadian physiology and what mechanism operates upstream is poorly understood. Here we report the sarcomere component TCAP as a cytoplasmic substrate of FBXL21. FBXL21 interacts with TCAP in a circadian manner antiphasic to TCAP accumulation in skeletal muscle, and circadian TCAP oscillation is disrupted in Psttm mice with an Fbxl21 hypomorph mutation. GSK-3β phosphorylates FBXL21 and TCAP to activate FBXL21-mediated, phosphodegron-dependent TCAP degradation. GSK-3β inhibition or knockdown diminishes FBXL21-Cul1 complex formation and delays FBXL21-mediated TCAP degradation. Finally, Psttm mice show significant skeletal muscle defects, including impaired fiber size, exercise tolerance, grip strength, and response to glucocorticoid-induced atrophy, in conjunction with cardiac dysfunction. These data highlight a circadian regulatory pathway where a GSK-3β-FBXL21 functional axis controls TCAP degradation via SCF complex formation and regulates skeletal muscle function.","journal":"Cell Reports","year":2020,"id":98015,"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":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":484371,"name":"Jiah Yang","orcid":"0000-0003-2312-8536","position":1,"is_corresponding":false},{"id":458441,"name":"Eunju Kim","orcid":"0000-0003-2235-470X","position":2,"is_corresponding":false},{"id":484372,"name":"Song Gao","orcid":"0000-0002-7225-2544","position":3,"is_corresponding":false},{"id":484373,"name":"Keshav Raj Paudel","orcid":"0000-0002-3591-2080","position":4,"is_corresponding":false},{"id":259926,"name":"Jong Min Choi","orcid":"0000-0002-5282-7697","position":5,"is_corresponding":false},{"id":484374,"name":"Jeehwan Choe","orcid":"0000-0002-7217-972X","position":6,"is_corresponding":false},{"id":484375,"name":"Gabrielle F. Gloston","orcid":"0000-0002-8830-3633","position":7,"is_corresponding":false},{"id":485526,"name":"Precious Ademoji","orcid":null,"position":8,"is_corresponding":false},{"id":485527,"name":"Randika Parakramaweera","orcid":null,"position":9,"is_corresponding":false},{"id":484376,"name":"Jianping Jin","orcid":"0000-0003-2722-0591","position":10,"is_corresponding":false},{"id":291924,"name":"Karyn A. Esser","orcid":"0000-0002-5791-1441","position":11,"is_corresponding":false},{"id":259925,"name":"Sung Yun Jung","orcid":"0000-0003-1521-7977","position":12,"is_corresponding":false},{"id":266740,"name":"Yong‐Jian Geng","orcid":"0000-0002-6835-7626","position":13,"is_corresponding":false},{"id":254730,"name":"Hyun Kyoung Lee","orcid":"0000-0001-5793-4398","position":14,"is_corresponding":false},{"id":458445,"name":"Zheng Chen","orcid":"0000-0002-2464-5474","position":15,"is_corresponding":false},{"id":484377,"name":"Seung‐Hee Yoo","orcid":"0000-0002-9930-560X","position":16,"is_corresponding":false},{"id":458442,"name":"Marvin Wirianto","orcid":"0000-0002-6933-0927","position":0,"is_corresponding":true}],"reference_count":93,"raw_metadata":null,"created_at":"2026-07-18T22:36:34.157932Z","pmid":"32937135","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":[]}