Class II transactivator (CIITA) is sufficient for the inducible expression of major histocompatibility complex class II genes.
Class II transactivator (CIITA) is sufficient for the inducible expression of major histocompatibility complex class II genes.
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DOI：
10.1084/jem.180.4.1367
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发表时间：
1994-10-01
期刊：
影响因子：
--
通讯作者：
Flavell RA
中科院分区：
文献类型：
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作者：
Chang CH;Fontes JD;Peterlin M;Flavell RA
II类反式激活因子（CIITA）已被证明是B细胞中主要组织相容性复合体（MHC）II类基因表达所需的，并且其缺陷是遗传性MHC II类缺陷的原因。在这里，我们表明，CIITA也参与了干扰素γ（IFN-γ）治疗后的诱导型II类基因的表达。CIITA的表达也可在诱导MHC II类mRNA之前用IFN-γ诱导。此外，CIITA mRNA表达不需要新的蛋白质合成，尽管新的蛋白质合成对于II类的转录是必需的。这表明，新的CIITA蛋白的合成可能是必不可少的诱导II类基因表达。我们还表明，JAK 1蛋白酪氨酸激酶活性是诱导CIITA表达IFN-γ刺激所必需的。这一发现表明CIITA是从IFN-γ受体到II类基因激活的信号级联的一部分。此外，CIITA的表达足以在没有IFN-γ刺激的情况下激活II类基因，表明CIITA是II类基因诱导表达的主要调节因子。总之，这些数据表明，CIITA是IFN-诱导放线菌酮敏感因子先前显示的诱导MHC II类基因表达所需的。
The class II transactivator (CIITA) has been shown to be required for major histocompatibility complex (MHC) class II gene expression in B cells and its deficiency is responsible for a hereditary MHC class II deficiency. Here we show that CIITA is also involved in the inducible expression of class II genes upon interferon gamma (IFN-gamma) treatment. The expression of CIITA is also inducible with IFN-gamma before the induction of MHC class II mRNA. In addition, CIITA mRNA expression does not require new protein synthesis, although new protein synthesis is necessary for the transcription of class II. This suggests that synthesis of new CIITA protein may be essential to induce class II gene expression. We also showed that the JAK1 protein tyrosine kinase activity is required to induce the expression of CIITA upon IFN-gamma stimulation. This finding indicates that CIITA is part of the signaling cascade from the IFN-gamma receptor to the activation of class II genes. In addition, the expression of CIITA is sufficient to activate class II genes in the absence of IFN-gamma stimulation suggesting that CIITA is the major regulatory factor for the inducible expression of class II genes. Together, these data suggest that CIITA is the IFN- inducible cycloheximide sensitive factor previously shown to be required for the induction of MHC class II gene expression.