Dendritic cell-specific MHC class II transactivator contains a caspase recruitment domain that confers potent transactivation activity
Dendritic cell-specific MHC class II transactivator contains a caspase recruitment domain that confers potent transactivation activity
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DOI：
10.1074/jbc.m101295200
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发表时间：
2001-06-01
影响因子：
4.8
通讯作者：
Chang, CH
中科院分区：
文献类型：
--
作者：
Nickerson, K;Sisk, TJ;Chang, CH
MHC II类反式激活因子（CIITA）是一种重要的转录因子，可调节参与抗原呈递功能的基因。CIITA基因产物的至少三种功能形式由三种不同的启动子转录。在树突状细胞中表达的CIITA基因（DC-CIITA）具有编码CIITA的延伸的N-末端区域的独特的第一外显子，在这里，我们表明DC-CIITA的N-末端与在细胞凋亡和核因子-KB信号通路的组分中发现的半胱天冬酶募集结构域（CARD）具有高度同源性。然而，DC-CIITA不调节细胞死亡，也不诱导核因子KB活性。相反，DC-CIITA在转录上是比在B细胞中表达的形式更有效的MHC II类基因的激活剂。预测破坏CARD-CARD相互作用的DC-CIITA的CARD中的单个氨基酸取代降低了DC-CIITA的反式激活潜力。这些结果表明，在CIITA的背景下，CARD充当转录活性的调节结构域，并且可以起到选择性地增强树突状细胞中MHC II类基因表达的作用。
The MHC class II transactivator (CIITA) is a critical transcription factor that regulates genes involved in antigen presentation function. At least three functional forms of CIITA gene products are transcribed from three different promoters. The CIITA gene expressed in dendritic cells (DC-CIITA) has a unique first exon encoding an extended N-terminal region of CIITA, Here, we show that the N terminus of DC-CIITA has high homology to a caspase recruitment domain (CARD) found in components of apoptosis and nuclear factor-KB signaling pathways. However, DC-CIITA does not regulate cell death, nor does it induce nuclear factor-KB activity. Instead, DC-CIITA is transcriptionally a more potent activator of the MHC class II gene than the form expressed in B cells. A single amino acid substitution in the CARD of DC-CIITA, predicted to disrupt CARD-CARD interactions, diminished the transactivation potential of DC-CIITA, These results indicate that the CARD in the context of CIITA serves as a regulatory domain for transcriptional activity and may function to selectively enhance MHC class II gene expression in dendritic cells.