NKAP is a transcriptional repressor of notch signaling and is required for T cell development.
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Pajerowski AG, Nguyen C, Aghajanian H, Shapiro MJ, Shapiro VS
NKAP is a transcriptional repressor of notch signaling and is required for T cell development.
Immunity. 2009 May;30(5):696-707. doi: 10.1016/j.immuni.2009.02.011. Epub 2009 Apr 30.
- PubMed ID
- 19409814 [ View in PubMed]
- 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 Lck(cre). Loss of NKAP blocked development of alphabeta but not gammadelta T cells, and Nkap(fl/o)Lck(cre) 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 alphabeta T cell development.