{"doi":"10.3390/cancers13030489","title":"Restoring the DREAM Complex Inhibits the Proliferation of High-Risk HPV Positive Human Cells","abstract":"High-risk (HR) human papillomaviruses are known causative agents in 5% of human cancers including cervical, ano-genital and head and neck carcinomas. In part, HR-HPV causes cancer by targeting host-cell tumor suppressors including retinoblastoma protein (pRb) and RB-like proteins p107 and p130. HR-HPV E7 uses a LxCxE motif to bind RB proteins, impairing their ability to control cell-cycle dependent transcription. E7 disrupts DREAM (Dimerization partner, RB-like, E2F and MuvB), a transcriptional repressor complex that can include p130 or p107, but not pRb, which regulates genes required for cell cycle progression. However, it is not known whether disruption of DREAM plays a significant role in HPV-driven tumorigenesis. In the DREAM complex, LIN52 is an adaptor that binds directly to p130 via an E7-like LxSxE motif. Replacement of the LxSxE sequence in LIN52 with LxCxE (LIN52-S20C) increases p130 binding and partially restores DREAM assembly in HPV-positive keratinocytes and human cervical cancer cells, inhibiting proliferation. Our findings demonstrate that disruption of the DREAM complex by E7 is an important process promoting cellular proliferation by HR-HPV. Restoration of the DREAM complex in HR-HPV positive cells may therefore have therapeutic benefits in HR-HPV positive cancers.","journal":"Cancers","year":2021,"id":188177,"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":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9463,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":715747,"name":"Siddharth Saini","orcid":"0000-0002-2813-9536","position":1,"is_corresponding":false},{"id":638740,"name":"Fatmata Sesay","orcid":"0000-0002-9973-3639","position":2,"is_corresponding":false},{"id":749104,"name":"Kevin Ko","orcid":null,"position":3,"is_corresponding":false},{"id":749105,"name":"Jessica Felthousen-Rusbasan","orcid":null,"position":4,"is_corresponding":false},{"id":651750,"name":"Audra N. Iness","orcid":"0000-0001-5194-1319","position":5,"is_corresponding":false},{"id":749106,"name":"Tara J. Nulton","orcid":null,"position":6,"is_corresponding":false},{"id":708386,"name":"Brad E. Windle","orcid":null,"position":7,"is_corresponding":false},{"id":265858,"name":"Mikhail G. Dozmorov","orcid":"0000-0002-0086-8358","position":8,"is_corresponding":false},{"id":325358,"name":"Iain M. Morgan","orcid":"0000-0002-4949-3032","position":9,"is_corresponding":false},{"id":397945,"name":"Larisa Litovchick","orcid":"0000-0002-9540-597X","position":10,"is_corresponding":false},{"id":325354,"name":"Claire D. James","orcid":"0000-0002-6816-1607","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-18T23:49:05.976005Z","pmid":"33513914","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":[]}