Recombinant p21 Protein Inhibits Lymphocyte Proliferation and Transcription Factors

• Published in: The Journal of immunology (1950) 2005-06, Vol.174 (12), p.7610-7617
• Main Authors: Khanna, Ashwani K, Plummer, Matthew, Nilakantan, Vani, Pieper, Galen M
• Format: Article
• Language: English
• Subjects: Active Transport, Cell Nucleus - immunology; Cell Cycle Proteins - biosynthesis; Cell Cycle Proteins - chemistry; Cell Cycle Proteins - isolation & purification; Cell Cycle Proteins - physiology; Cell Nucleus - metabolism; Cell Proliferation - drug effects; Cyclin-Dependent Kinase Inhibitor p21; Cyclosporine - pharmacology; Cytokines - antagonists & inhibitors; Cytokines - biosynthesis; Cytokines - metabolism; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - metabolism; Growth Inhibitors - physiology; Humans; Immunosuppressive Agents - pharmacology; Interleukin-2 - antagonists & inhibitors; Interleukin-2 - biosynthesis; Interleukin-2 - genetics; Lymphocyte Activation - drug effects; Lymphocyte Subsets - cytology; Lymphocyte Subsets - metabolism; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NFATC Transcription Factors; Nuclear Proteins - antagonists & inhibitors; Nuclear Proteins - metabolism; Recombinant Proteins - metabolism; Recombinant Proteins - pharmacology; RNA, Messenger - antagonists & inhibitors; RNA, Messenger - biosynthesis; Sirolimus - pharmacology; T-Lymphocytes - metabolism; Tacrolimus - pharmacology; Transcription Factors - antagonists & inhibitors; Transcription Factors - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.174.12.7610

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.