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

被引：79

作者：

Pajerowski, Anthony G. ^{[1
,2
]}

Nguyen, Chau ^{[1
]}

Aghajanian, Haig ^{[1
]}

Shapiro, Michael J. ^{[1
,2
]}

Shapiro, Virginia Smith ^{[1
,2
]}

机构：

[1] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[2] Mayo Clin, Dept Immunol, Rochester, MN 55905 USA

来源：

IMMUNITY | 2009年 / 30卷 / 05期

关键词：

ACUTE LYMPHOBLASTIC-LEUKEMIA; VULVAL DEVELOPMENT; ALPHA-BETA; PROTEIN; DIFFERENTIATION; EXPRESSION; RECEPTOR; PATHWAY; COMPLEX; COREPRESSOR;

D O I：

10.1016/j.immuni.2009.02.011

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 alpha beta but not gamma delta 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 alpha beta T cell development.

引用

页码：696 / 707

页数：12

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