The ETS protein MEF plays a critical role in perforin gene expression and the development of natural killer and NK-T cells Journal Article
| Authors: | Lacorazza, H. D.; Miyazaki, Y.; Di Cristofano, A.; Deblasio, A.; Hedvat, C.; Zhang, J.; Cordon-Cardo, C.; Mao, S.; Pandolfi, P. P.; Nimer, S. D. |
| Article Title: | The ETS protein MEF plays a critical role in perforin gene expression and the development of natural killer and NK-T cells |
| Abstract: | We utilized gene targeting by homologous recombination to define the role that MEF, a transcriptional activating member of the ETS family of transcription factors, plays in lymphopoiesis. MEF-/- mice have a profound reduction in the number of NK-T and NK cells. Purified MEF-/- NK cells cannot lyse tumor cell targets and secrete only minimal amounts of IFNγ. Perforin protein expression is severely impaired in MEF-deficient NK cells, likely accounting for the lack of tumor cell cytotoxicity. Promoter studies and chromatin immunoprecipitation analyses demonstrate that MEF and not ETS-1 directly regulates transcription of the perforin gene in NK cells. Our results uncover a specific role of MEF in the development and function of NK cells and in innate immunity. |
| Keywords: | controlled study; unclassified drug; dna-binding proteins; nonhuman; protein function; t lymphocyte; animal cell; mouse; animals; mice; mice, knockout; gene; homologous recombination; gene targeting; cell function; gene expression; cell maturation; transcription factor; genetic transcription; cytotoxicity; b-lymphocytes; transcription factors; gene expression regulation; cellular immunity; gamma interferon; membrane glycoproteins; chromatin; tumor cell; immunoprecipitation; natural killer cell; killer cells, natural; perforin; cytolysis; cytotoxicity, immunologic; t-lymphocyte subsets; protein family; lymphopoiesis; lymphocytes; transcription factor ets; cell secretion; genetic regulation; promoter regions (genetics); pore forming cytotoxic proteins; transcription factor mef; priority journal; article |
| Journal Title: | Immunity |
| Volume: | 17 |
| Issue: | 4 |
| ISSN: | 1074-7613 |
| Publisher: | Cell Press |
| Date Published: | 2002-10-01 |
| Start Page: | 437 |
| End Page: | 449 |
| Language: | English |
| DOI: | 10.1016/s1074-7613(02)00422-3 |
| PUBMED: | 12387738 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work