{"doi":"10.17615/r2wm-9n73","title":"Intrinsic Negative Cell Cycle Regulation Provided by PIP Box- and Cul4Cdt2-Mediated Destruction of E2f1 during S Phase","abstract":"E2F transcription factors are key regulators of cell proliferation that are inhibited by pRb family tumor suppressors. pRb-independent modes of E2F inhibition have also been described, but their contribution to animal development and tumor suppression is unclear. Here we show that S phase-specific destruction of Drosophila E2f1 provides a novel mechanism for cell cycle regulation. E2f1 destruction is mediated by a PCNA-interacting-protein (PIP) motif in E2f1 and the Cul4Cdt2 E3 ubiquitin ligase, and requires the Dp dimerization partner but not direct Cdk phosphorylation or Rbf1 binding. E2f1 lacking a functional PIP motif accumulates inappropriately during S phase and is more potent than wild type E2f1 at accelerating cell cycle progression and inducing apoptosis. Thus, S phase-coupled destruction is a key negative regulator of E2f1 activity. We propose that pRb-independent inhibition of E2F during S phase is an evolutionarily conserved feature of the metazoan cell cycle that is necessary for development.","journal":"UNC Libraries","year":2020,"id":139716,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9442,"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":603810,"name":"William J. Turbyfill","orcid":null,"position":1,"is_corresponding":false},{"id":89527,"name":"Vuong K. Tran","orcid":"0000-0002-2564-0202","position":2,"is_corresponding":false},{"id":596061,"name":"Shusaku Shibutani","orcid":"0000-0001-6804-5094","position":3,"is_corresponding":false},{"id":291158,"name":"Robert J. Duronio","orcid":"0000-0001-6469-6965","position":4,"is_corresponding":false},{"id":596058,"name":"Bruce A. Edgar","orcid":"0000-0002-3383-2044","position":5,"is_corresponding":false},{"id":603811,"name":"Aida Flor A. de la Cruz","orcid":null,"position":6,"is_corresponding":false},{"id":603289,"name":"Tânia Reis","orcid":"0000-0001-6879-1265","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:17:13.583586Z","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":[]}