{"doi":"10.1128/mcb.19.1.353","title":"Cyclin D- and E-Dependent Kinases and the p57<sup><i>KIP2</i></sup> Inhibitor: Cooperative Interactions In Vivo","abstract":null,"journal":"Molecular and Cellular Biology","year":1999,"id":650014,"datarank":0.637274286307404,"base_score":4.248495242049359,"endowment":4.248495242049359,"self_citation_contribution":0.637274286307404,"citation_network_contribution":0.0,"self_endowment_contribution":0.637274286307404,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":69,"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":1694779,"name":"Nanette J. Liegeois","orcid":null,"position":1,"is_corresponding":false},{"id":148886,"name":"Pumin Zhang","orcid":null,"position":2,"is_corresponding":false},{"id":407730,"name":"Jeffrey A. Engelman","orcid":"0009-0004-0775-4523","position":3,"is_corresponding":false},{"id":1694781,"name":"James Horner","orcid":null,"position":4,"is_corresponding":false},{"id":1694782,"name":"Adam Silverman","orcid":null,"position":5,"is_corresponding":false},{"id":1694783,"name":"Ronald Burde","orcid":null,"position":6,"is_corresponding":false},{"id":260237,"name":"Martine F. Roussel","orcid":"0000-0002-1740-8139","position":7,"is_corresponding":false},{"id":228782,"name":"Charles J. Sherr","orcid":"0000-0002-5516-6206","position":8,"is_corresponding":false},{"id":108430,"name":"Stephen J. Elledge","orcid":"0000-0001-7923-6283","position":9,"is_corresponding":false},{"id":7904,"name":"Ronald A. DePinho","orcid":"0000-0002-5625-577X","position":10,"is_corresponding":false},{"id":1694778,"name":"Enrique Gómez Lahoz","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Cyclin D- and E-Dependent Kinases and the p57<sup><i>KIP2</i></sup> Inhibitor: Cooperative Interactions In Vivo","abstract":"This study examines in vivo the role and functional interrelationships of components regulating exit from the G1 resting phase into the DNA synthetic (S) phase of the cell cycle. Our approach made use of several key experimental attributes of the developing mouse lens, namely its strong dependence on pRb in maintenance of the postmitotic state, the down-regulation of cyclins D and E and up-regulation of the p57(KIP2) inhibitor in the postmitotic lens fiber cell compartment, and the ability to target transgene expression to this compartment. These attributes provide an ideal in vivo context in which to examine the consequences of forced cyclin expression and/or of loss of p57(KIP2) inhibitor function in a cellular compartment that permits an accurate quantitation of cellular proliferation and apoptosis rates in situ. Here, we demonstrate that, despite substantial overlap in cyclin transgene expression levels, D-type and E cyclins exhibited clear functional differences in promoting entry into S phase. In general, forced expression of the D-type cyclins was more efficient than cyclin E in driving lens fiber cells into S phase. In the case of cyclins D1 and D2, ectopic proliferation required their enhanced nuclear localization through CDK4 coexpression. High nuclear levels of cyclin E and CDK2, while not sufficient to promote efficient exit from G1, did act synergistically with ectopic cyclin D/CDK4. The functional differences between D-type and E cyclins was most evident in the p57(KIP2)-deficient lens wherein cyclin D overexpression induced a rate of proliferation equivalent to that of the pRb null lens, while overexpression of cyclin E did not increase the rate of proliferation over that induced by the loss of p57(KIP2) function. These in vivo analyses provide strong biological support for the prevailing view that the antecedent actions of cyclin D/CDK4 act cooperatively with cyclin E/CDK2 and antagonistically with p57(KIP2) to regulate the G1/S transition in a cell type highly dependent upon pRb.","is_dataset_classified":null,"base_score":4.248495242049359,"endowment":4.248495242049359,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"9858559","pmcid":"PMC83893","openalex_id":"https://openalex.org/W2125213265","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"P30 CA013330","title":null},{"funder_name":"NEI NIH HHS","grant_id":"R01EY11267","title":null},{"funder_name":"NICHD NIH HHS","grant_id":"R01HD28317","title":null},{"funder_name":"NIA NIH HHS","grant_id":"T32 AG000194","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"T32 GM007288","title":null},{"funder_name":"NEI NIH HHS","grant_id":"R01EY09300","title":null},{"funder_name":"National Institutes of Health","grant_id":"3P30CA013330-39S3","title":"Core Support for Cancer Center"},{"funder_name":"National Institutes of Health","grant_id":"2T32GM007288-24","title":"MEDICAL SCIENTIST TRAINING PROGRAM"},{"funder_name":"National Institutes of Health","grant_id":"5R01EY011267-06","title":"ROLE AND REGULATION OF CDK4 IN THE NORMAL LENS"},{"funder_name":"National Institutes of Health","grant_id":"5T32AG000194-08","title":"AGING TRAINING GRANT"},{"funder_name":"National Institutes of Health","grant_id":"1R01HD028317-01","title":"N-MYC EXPRESSION AND ACTIVITY IN CANCER AND DEVELOPMENT"}],"total_grants":11,"fwci":1.8011,"citation_percentile":0.84970397,"influential_citations":0,"citation_trend":[{"year":2012,"count":1},{"year":2013,"count":1},{"year":2014,"count":1},{"year":2015,"count":2},{"year":2016,"count":1},{"year":2017,"count":1},{"year":2019,"count":1},{"year":2020,"count":1},{"year":2022,"count":2},{"year":2023,"count":2}],"oa_status":"bronze","license":"ASM Journals Non-Commercial TDM","oa_locations":[{"url":"https://mcb.asm.org/content/mcb/19/1/353.full.pdf","host_type":"journal"},{"url":"https://mcb.asm.org/content/mcb/19/1/353.full.pdf","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/MCB.19.1.353","host_type":"publisher"},{"url":"https://www.tandfonline.com/doi/pdf/10.1128/MCB.19.1.353","host_type":"publisher"},{"url":"https://doi.org/10.1128/mcb.19.1.353","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/9858559","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/83893","host_type":"repository"},{"url":"https://dx.doi.org/10.1128/mcb.19.1.353","host_type":""}],"fields_of_study":["Cancer-related Molecular Pathways","Urological Disorders and Treatments","Aldose Reductase and Taurine","0301 basic medicine","0303 health sciences","03 medical and health sciences","Animals","Apoptosis","Biological Transport","CDC2-CDC28 Kinases","Cell Nucleus","Crystallins","Cyclin D1","Cyclin D2","Cyclin E","Cyclin-Dependent Kinase 2","Cyclin-Dependent Kinase 4","Cyclin-Dependent Kinase Inhibitor p57","Cyclin-Dependent Kinases","Cyclins","Enzyme Inhibitors","Female","G1 Phase","Male","Mice","Mice, Inbred C57BL","Mice, Transgenic","Nuclear Proteins","Protein Serine-Threonine Kinases","Proto-Oncogene Proteins","S Phase"],"mesh_terms":["Animals","Biological Transport","Cell Nucleus","Crystallins","Enzyme Inhibitors","Female","Male","Mice, Inbred C57BL","Mice, Transgenic","Nuclear Proteins","Proto-Oncogene Proteins","G1 Phase","S Phase","Cyclins","Apoptosis","Protein Serine-Threonine Kinases","Cyclin-Dependent Kinases","Cyclin E","Cyclin D1","CDC2-CDC28 Kinases","Cyclin-Dependent Kinase Inhibitor p57","Cyclin-Dependent Kinase 2","Cyclin-Dependent Kinase 4","Mice","Cyclin D2"],"keywords":["Cyclin","Biology","Cyclin A","Cyclin E","Cell biology","Cyclin D","Cyclin A2","Cell cycle","Ectopic expression","Cyclin-dependent kinase","Cyclin E1","Cyclin D1","Kinase","Cell growth","Molecular 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