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

H. Daniel Lacorazza, Yasushi Miyazaki, Antonio Di Cristofano, Anthony Deblasio, Cyrus Hedvat, Jin Zhang, Carlos Cordon-Cardo, Shifeng Mao, Pier Paolo Pandolfi, Stephen D. Nimer

Research output: Contribution to journalArticle

150 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)437-449
Number of pages13
JournalImmunity
Volume17
Issue number4
DOIs
StatePublished - Oct 1 2002
Externally publishedYes

Fingerprint

Perforin
Natural Killer T-Cells
Natural Killer Cells
Gene Expression
Proteins
Lymphopoiesis
Gene Targeting
Chromatin Immunoprecipitation
Homologous Recombination
Innate Immunity
Neoplasms
Transcription Factors
Genes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

The ETS protein MEF plays a critical role in perforin gene expression and the development of natural killer and NK-T cells. / Lacorazza, H. Daniel; Miyazaki, Yasushi; Di Cristofano, Antonio; Deblasio, Anthony; Hedvat, Cyrus; Zhang, Jin; Cordon-Cardo, Carlos; Mao, Shifeng; Pandolfi, Pier Paolo; Nimer, Stephen D.

In: Immunity, Vol. 17, No. 4, 01.10.2002, p. 437-449.

Research output: Contribution to journalArticle

Lacorazza, HD, Miyazaki, Y, Di Cristofano, A, Deblasio, A, Hedvat, C, Zhang, J, Cordon-Cardo, C, Mao, S, Pandolfi, PP & Nimer, SD 2002, 'The ETS protein MEF plays a critical role in perforin gene expression and the development of natural killer and NK-T cells', Immunity, vol. 17, no. 4, pp. 437-449. https://doi.org/10.1016/S1074-7613(02)00422-3
Lacorazza, H. Daniel ; Miyazaki, Yasushi ; Di Cristofano, Antonio ; Deblasio, Anthony ; Hedvat, Cyrus ; Zhang, Jin ; Cordon-Cardo, Carlos ; Mao, Shifeng ; Pandolfi, Pier Paolo ; Nimer, Stephen D. / The ETS protein MEF plays a critical role in perforin gene expression and the development of natural killer and NK-T cells. In: Immunity. 2002 ; Vol. 17, No. 4. pp. 437-449.
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