{"doi":"10.1016/j.cell.2011.04.002","title":"NEMO/NLK Phosphorylates PERIOD to Initiate a Time-Delay Phosphorylation Circuit that Sets Circadian Clock Speed","abstract":null,"journal":"Cell","year":2011,"id":601807,"datarank":0.7830533737617489,"base_score":5.220355825078325,"endowment":5.220355825078325,"self_citation_contribution":0.7830533737617489,"citation_network_contribution":0.0,"self_endowment_contribution":0.7830533737617489,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":184,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1543148,"name":"Hyuk Wan Ko","orcid":null,"position":1,"is_corresponding":false},{"id":1127796,"name":"Isaac Edery","orcid":"0000-0001-9357-9055","position":2,"is_corresponding":false},{"id":1543147,"name":"Joanna C. Chiu","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"NEMO/NLK Phosphorylates PERIOD to Initiate a Time-Delay Phosphorylation Circuit that Sets Circadian Clock Speed","abstract":"The speed of circadian clocks in animals is tightly linked to complex phosphorylation programs that drive daily cycles in the levels of PERIOD (PER) proteins. Using Drosophila, we identify a time-delay circuit based on hierarchical phosphorylation that controls the daily downswing in PER abundance. Phosphorylation by the NEMO/NLK kinase at the \"per-short\" domain on PER stimulates phosphorylation by DOUBLETIME (DBT/CK1δ/ɛ) at several nearby sites. This multisite phosphorylation operates in a spatially oriented and graded manner to delay progressive phosphorylation by DBT at other more distal sites on PER, including those required for recognition by the F box protein SLIMB/β-TrCP and proteasomal degradation. Highly phosphorylated PER has a more open structure, suggesting that progressive increases in global phosphorylation contribute to the timing mechanism by slowly increasing PER susceptibility to degradation. Our findings identify NEMO as a clock kinase and demonstrate that long-range interactions between functionally distinct phospho-clusters collaborate to set clock speed.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21514639","pmcid":"PMC3092788","openalex_id":null,"authors":[],"funders":[{"funder_name":"NINDS NIH HHS","grant_id":"R00 NS061952","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"K99/R00NS061952","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"R01 NS034958","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"R01NS03498","title":null}],"total_grants":4,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"bronze","license":"http://www.elsevier.com/open-access/userlicense/1.0/","oa_locations":[{"url":"http://www.cell.com/article/S0092867411003850/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0092867411003850?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0092867411003850?httpAccept=text/plain","host_type":"publisher"}],"fields_of_study":[],"mesh_terms":["Cell Line","Animals","Animals, Genetically Modified","Drosophila melanogaster","Ubiquitin-Protein Ligases","Mitogen-Activated Protein Kinases","Cell Cycle Proteins","Drosophila Proteins","Amino Acid Sequence","Phosphorylation","Molecular Sequence Data","Period Circadian Proteins","Circadian Clocks","Casein Kinase 1 epsilon"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T17:30:08.830626Z","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,"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":[]}