The ETS protein MEF plays a critical role in perforin gene expression and the development of natural killer and NK-T cells

The ETS protein MEF plays a critical role in perforin gene expression and the development of natural killer and NK-T cells
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DOI:
10.1016/s1074-7613(02)00422-3
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发表时间:
2002-10-01
期刊:
影响因子:
32.4
通讯作者:
Nimer, SD
Nimer, SD
中科院分区:
医学1区
文献类型:
--
作者:
Lacorazza, HD;Miyazaki, Y;Nimer, SD

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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 IFNgamma. 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.