NKAP是Notch信号通路的转录抑制因子，是T细胞发育所必需的。
NKAP is a transcriptional repressor of notch signaling and is required for T cell development.
作者信息
Pajerowski Anthony G, Nguyen Chau, Aghajanian Haig, Shapiro Michael J, Shapiro Virginia Smith
机构信息
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
出版信息
Immunity. 2009 May;30(5):696-707. doi: 10.1016/j.immuni.2009.02.011. Epub 2009 Apr 30.
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.
T细胞的发育依赖于受体信号传导与转录调控之间的协同相互作用。通过基因互补筛选，鉴定出一种转录抑制因子NKAP。NKAP与组蛋白去乙酰化酶HDAC3相关联，并且如染色质免疫沉淀所证明的那样，它是DNA结合复合物的一部分。NKAP还与Notch共抑制复合物相关联。T细胞发育过程中NKAP的表达与Notch靶基因的表达呈负相关，这意味着NKAP可能调节Notch介导的转录。为了研究NKAP在T细胞发育中的功能，我们通过Lck(cre)敲除了NKAP。NKAP的缺失阻断了αβ T细胞而非γδ T细胞的发育，并且Nkap(fl/o)Lck(cre)双阳性（DP）T细胞中Hes1、Deltex1和CD25 mRNA的表达量高8至20倍。因此，NKAP作为一种转录抑制因子，作用于Notch靶基因，是αβ T细胞发育所必需的。
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