{"doi":"10.17615/be8j-0q75","title":"An Important Role of CDK Inhibitor p18INK4c in Modulating Antigen Receptor-Mediated T Cell Proliferation","abstract":"The inhibitors of cyclin-dependent kinase (CDK) 4 (INK4) bind CDK4/6 to prevent their association with D-cyclins and G1 cell cycle initiation and progression. We report here that among the seven CDK inhibitors, p18INK4c played an important role in modulating TCR-mediated T cell proliferation. Loss of p18INK4c in T cells led to hyperproliferation in response to CD3 stimulation. p18INK4c-null mice developed lymphoproliferative disorder and T cell lymphomas. Expression of IL-2, IL-2R-a, and the major G1 cell cycle regulatory proteins was not altered in p18-null T cells. Both FK506 and rapamycin efficiently inhibited proliferation of p18-null T cells. In activated T cells, p18INK4c remained constant, and preferentially associated with and inhibited CDK6 but not CDK4. We propose that p18INK4c sets an inhibitory threshold in T cells and one function of CD28 costimulation is to counteract the p18INK4c inhibitory activity on CDK6-cyclin D complexes. The p18INK4c protein may provide a novel target to modulate T cell immunity.","journal":"UNC Libraries","year":2020,"id":114769,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"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":540046,"name":"Vernon M. Coffield","orcid":null,"position":1,"is_corresponding":false},{"id":322894,"name":"Yuan Xiong","orcid":"0000-0003-3461-8688","position":2,"is_corresponding":false},{"id":392250,"name":"Kovalev Gi","orcid":"0000-0003-4346-3585","position":3,"is_corresponding":false},{"id":392251,"name":"David S. Franklin","orcid":"0009-0009-0731-9093","position":4,"is_corresponding":false},{"id":255662,"name":"Lishan Su","orcid":"0000-0002-0350-5560","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:13:33.226937Z","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":[]}