Département de Biologie, Université de Sherbrooke, 2500 Boul., Sherbrooke, QC J1K 2R1, Canada.
Int J Mol Sci. 2021 Jan 22;22(3):1074. doi: 10.3390/ijms22031074.
In this review, we discuss the major histocompatibility complex (MHC) class II transactivator (CIITA), which is the master regulator of MHC class II gene expression. CIITA is the founding member of the mammalian nucleotide-binding and leucine-rich-repeat (NLR) protein family but stood apart for a long time as the only transcriptional regulator. More recently, it was found that its closest homolog, NLRC5 (NLR protein caspase activation and recruitment domain (CARD)-containing 5), is a regulator of MHC-I gene expression. Both act as non-DNA-binding activators through multiple protein-protein interactions with an MHC enhanceosome complex that binds cooperatively to a highly conserved combinatorial cis-acting module. Thus, the regulation of MHC-II expression is regulated largely through the differential expression of CIITA. In addition to the well-defined role of CIITA in MHC-II GENE regulation, we will discuss several other aspects of CIITA functions, such as its role in cancer, its role as a viral restriction element contributing to intrinsic immunity, and lastly, its very recently discovered role as an inhibitor of Ebola and SARS-Cov-2 virus replication. We will briefly touch upon the recently discovered role of NLRP3 as a transcriptional regulator, which suggests that transcriptional regulation is, after all, not such an unusual feature for NLR proteins.
在这篇综述中，我们讨论了主要组织相容性复合体 (MHC) Ⅱ类转录激活因子 (CIITA)，它是 MHC Ⅱ类基因表达的主要调节因子。CIITA 是哺乳动物核苷酸结合和富含亮氨酸重复 (NLR) 蛋白家族的创始成员，但长期以来一直是唯一的转录调节因子。最近，发现其最接近的同源物 NLRC5（含有 caspase 激活和募集结构域 (CARD) 的 NLR 蛋白 5）是 MHC-I 基因表达的调节因子。两者都通过与 MHC 增强子复合物的多种蛋白-蛋白相互作用作为非 DNA 结合激活剂起作用，该复合物与高度保守的组合顺式作用模块协同结合。因此，MHC-II 表达的调节主要通过 CIITA 的差异表达来调节。除了 CIITA 在 MHC-II 基因调控中的明确作用外，我们还将讨论 CIITA 功能的其他几个方面，例如它在癌症中的作用、作为有助于固有免疫的病毒限制因子的作用，以及最近发现的作为埃博拉病毒和 SARS-CoV-2 病毒复制抑制剂的作用。我们将简要讨论 NLRP3 作为转录调节因子的新发现作用，这表明转录调节毕竟不是 NLR 蛋白的一个不寻常特征。
