NKAP Is a Transcriptional Repressor of Notch Signaling and Is Required for T Cell Development

Anthony G. Pajerowski, Chau Nguyen, Haig Aghajanian, Michael J. Shapiro, Virginia Smith Shapiro

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

T cell development depends on the coordinated interplay between receptor signaling and transcriptional regulation. Through a genetic complementation screen a transcriptional repressor, NKAP, was identified. NKAP associated with the histone deacetylase HDAC3 and was shown to be part of a DNA-binding complex, as demonstrated by chromatin immunoprecipitation. NKAP also associated with the Notch corepressor complex. The expression of NKAP during T cell development inversely correlated with the expression of Notch target genes, implying that NKAP may modulate Notch-mediated transcription. To examine the function of NKAP in T cell development, we ablated NKAP by Lckcre. Loss of NKAP blocked development of αβ but not γδ T cells, and Nkapfl/oLckcre DP T cells expressed 8- to 20-fold higher amounts of Hes1, Deltex1, and CD25 mRNA. Thus, NKAP functions as a transcriptional repressor, acting on Notch target genes, and is required for αβ T cell development.

Original languageEnglish (US)
Pages (from-to)696-707
Number of pages12
JournalImmunity
Volume30
Issue number5
DOIs
StatePublished - May 22 2009

Keywords

  • CELLIMMUNO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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