{"doi":"10.1126/sciadv.abb3154","title":"Cross-talk between CDK4/6 and SMYD2 regulates gene transcription, tubulin methylation, and ciliogenesis","abstract":"Dysregulation of cyclin-dependent kinases 4 and 6 (CDK4/6) by unknown mechanisms is highly prevalent in human disease. In this study, we identify direct cross-talk between CDK4/6 and the epigenome via its previously unidentified substrate, SMYD2, a histone/lysine methyltransferase. CDK4/6 positively regulates the phosphorylation and enzymatic activity of SMYD2, while SMYD2 also positively regulates the expression of CDK4/6. We also identify SMYD2 as an α-tubulin methyltransferase, thus connecting CDK4/6-SMYD2 signaling to microtubule dynamics. In addition, depletion or inhibition of CDK4/6 and SMYD2 resulted in increased cilia assembly by affecting (i) microtubule stability and (ii) the expression of IFT20, further connecting CDK4/6-SMYD2 to ciliogenesis. In clinical settings such as breast cancer and autosomal dominant polycystic kidney disease (ADPKD), targeting the up-regulated CDK4/6 and SMYD2 with inhibitors results in restoration of the primary cilium in tumor and cystic cells, which may normalize cilia-mediated extracellular signals that regulate growth, development, and cellular homeostasis.","journal":"Science Advances","year":2020,"id":67192,"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":48,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"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":355979,"name":"Julie Zhou","orcid":"0000-0002-4876-4080","position":1,"is_corresponding":false},{"id":355980,"name":"Xiaodong Wang","orcid":"0000-0002-5140-0974","position":2,"is_corresponding":false},{"id":355981,"name":"Hongbing Zhang","orcid":"0000-0001-7119-7304","position":3,"is_corresponding":false},{"id":318231,"name":"Peter C. Harris","orcid":"0000-0002-5304-6593","position":4,"is_corresponding":false},{"id":355982,"name":"James P. Calvet","orcid":"0000-0001-5928-9820","position":5,"is_corresponding":false},{"id":353525,"name":"Xiaogang Li","orcid":"0000-0001-8135-342X","position":6,"is_corresponding":false},{"id":355978,"name":"Xiaoyan Li","orcid":"0000-0002-7460-0776","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-18T21:15:12.020735Z","pmid":"33127671","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":[]}