Direct manipulation of activator protein-1 controls thymocyte proliferation in vitro
| Autor: | Alfred J. Zullo, Elizabeth J. Taparowsky, Kristi L. Williams, Tina M. Thornton |
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| Rok vydání: | 2006 |
| Předmět: |
Time Factors
Transcription Genetic T-Lymphocytes Transgene Immunoblotting Immunology Activating transcription factor Electrophoretic Mobility Shift Assay Mice Transgenic In Vitro Techniques Biology Lymphocyte Activation Polymerase Chain Reaction Mice chemistry.chemical_compound Transcription (biology) BATF Animals Immunology and Allergy RNA Messenger Promoter Regions Genetic Cell Proliferation Microscopy Confocal Activator (genetics) Molecular biology Transcription Factor AP-1 Thymocyte chemistry Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Ionomycin Expression cassette |
| Zdroj: | European Journal of Immunology. 36:160-169 |
| ISSN: | 1521-4141 0014-2980 |
| DOI: | 10.1002/eji.200535215 |
| Popis: | B cell activating transcription factor (BATF) belongs to the activator protein-1 (AP-1) superfamily of basic leucine zipper transcription factors and forms heterodimers with Jun that possess minimal transcriptional activity. Mice carrying a p56(lck)HA-BATF transgene were created to observe the effects of constitutive expression of this well-characterized AP-1 inhibitor on T cell proliferation. Consistent with the role of AP-1 in promoting the proliferation of many cell types, BATF-transgenic thymocytes proliferate poorly in vitro when stimulated with anti-CD3epsilon and anti-CD28 antibodies or with Concanavalin A. However, when BATF-transgenic thymocytes were stimulated using a standard treatment of PMA and ionomycin, proliferation is normal. The responsiveness to PMA and ionomycin can be attributed to the dramatic disappearance of the hemagglutinin antigen (HA)-tagged BATF protein which is a PKC-dependent process caused by the down-regulation of the p56(lck) proximal promoter coupled with the rapid turnover of the HA-BATF protein. These studies describe conditions of T cell stimulation that negatively influence transcription of the widely used p56(lck) proximal promoter expression cassette. In addition, the unique circumstances of this regulation were exploited to demonstrate that inhibition of AP-1 activity by BATF exerts a direct, and reversible, effect on T cell proliferation in vitro. |
| Databáze: | OpenAIRE |
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