CIITA的一个36个氨基酸的区域是CBP的有效抑制剂：γ干扰素介导的对胶原蛋白α(2)(I)及其他启动子抑制的新机制。
A 36-amino-acid region of CIITA is an effective inhibitor of CBP: novel mechanism of gamma interferon-mediated suppression of collagen alpha(2)(I) and other promoters.
作者信息
Zhu X S, Ting J P
机构信息
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, USA.
出版信息
Mol Cell Biol. 2001 Oct;21(20):7078-88. doi: 10.1128/MCB.21.20.7078-7088.2001.
Abstract
The class II transactivator (CIITA) is induced by gamma interferon (IFN-gamma) and activates major histocompatibility complex class II; however, this report shows it suppresses other genes. An N-terminal 36 amino acids of CIITA mediates suppression of the collagen alpha(2)(I) promoter via binding to CREB-binding protein (CBP). Reconstitution of cells with CBP reverts this suppression. IFN-gamma is known to inhibit collagen gene expression; to test if CIITA mediates this gene suppression, a mutant cell line defective in CIITA induction but not in the activation of STAT1/JAK/IRF-1 is studied. IFN-gamma suppression of the collagen promoter and the endogenous gene is observed in the wild-type control but not in the mutant line. Suppression is restored when CIITA is introduced. Other targets of CIITA-mediated promoter suppression include interleukin 4, thymidine kinase, and cyclin D1.
摘要
II类反式激活因子（CIITA）由γ干扰素（IFN-γ）诱导产生，并激活主要组织相容性复合体II类分子；然而，本报告显示它可抑制其他基因。CIITA的N端36个氨基酸通过与CREB结合蛋白（CBP）结合介导对胶原蛋白α(2)(I)启动子的抑制作用。用CBP重建细胞可逆转这种抑制作用。已知IFN-γ可抑制胶原蛋白基因表达；为了检测CIITA是否介导这种基因抑制作用，研究了一种在CIITA诱导方面存在缺陷但在STAT1/JAK/IRF-1激活方面无缺陷的突变细胞系。在野生型对照中观察到IFN-γ对胶原蛋白启动子和内源性基因的抑制作用，但在突变细胞系中未观察到。当导入CIITA时，抑制作用得以恢复。CIITA介导的启动子抑制作用的其他靶点包括白细胞介素4、胸苷激酶和细胞周期蛋白D1。
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