title: Recombinant p21 protein inhibits lymphocyte proliferation and transcription factors.
abstract: Cellular proliferation determines the events leading to the initiation and development of inflammation, immune activation, cancer, atherogenesis, and other disorders associated with aberrant cell proliferation. Cyclin inhibitor p21 plays a unique role in limiting cell cycle progression. However, its effectiveness can only be demonstrated with direct in vitro and in vivo delivery to control aberrant proliferation. We demonstrate that using a protein-transducing domain p21 protein a) localizes within the nuclear compartments of cells, b) interacts with transcription factors, NF-kappaB, and NFATs (NFATc and NFATp), and c) inhibits lymphocyte proliferation and expression of proinflammatory cytokines. This study using lymphocyte proliferation as a model suggests that the recombinant p21 protein can directly be delivered as a therapeutic protein to provide a novel, viable, and powerful strategy to limit proliferation, inflammation, alloimmune activation, cancer, and vascular proliferative disorders such as atherosclerosis.
authors.affiliation: Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA. akkhanna@mcw.edu
authors.forename: Ashwani K
authors.initials: AK
authors.lastname: Khanna
authors.forename: Matthew
authors.initials: M
authors.lastname: Plummer
authors.forename: Vani
authors.initials: V
authors.lastname: Nilakantan
authors.forename: Galen M
authors.initials: GM
authors.lastname: Pieper
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000276:immunology; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006131:Growth Inhibitors / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects; D016131:Lymphocyte Subsets / Q000166:cytology* / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D020123:Sirolimus / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016207:Cytokines; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014157:Transcription Factors; D016572:Cyclosporine; D020123:Sirolimus; D016559:Tacrolimus