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The MHC Class II Transactivator CIITA: Not (Quite) the Odd-One-Out Anymore among NLR Proteins

Département de Biologie, Université de Sherbrooke, 2500 Boul., Sherbrooke, QC J1K 2R1, Canada
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(3), 1074; https://doi.org/10.3390/ijms22031074
Received: 23 December 2020 / Revised: 15 January 2021 / Accepted: 19 January 2021 / Published: 22 January 2021
(This article belongs to the Special Issue The Diversity of Mammalian Nod-Like Receptor Functions)
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. View Full-Text
Keywords: CIITA; NLRC5; MHC genes; gene regulation CIITA; NLRC5; MHC genes; gene regulation
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MDPI and ACS Style

León Machado, J.A.; Steimle, V. The MHC Class II Transactivator CIITA: Not (Quite) the Odd-One-Out Anymore among NLR Proteins. Int. J. Mol. Sci. 2021, 22, 1074. https://doi.org/10.3390/ijms22031074

AMA Style

León Machado JA, Steimle V. The MHC Class II Transactivator CIITA: Not (Quite) the Odd-One-Out Anymore among NLR Proteins. International Journal of Molecular Sciences. 2021; 22(3):1074. https://doi.org/10.3390/ijms22031074

Chicago/Turabian Style

León Machado, Jorge A.; Steimle, Viktor. 2021. "The MHC Class II Transactivator CIITA: Not (Quite) the Odd-One-Out Anymore among NLR Proteins" Int. J. Mol. Sci. 22, no. 3: 1074. https://doi.org/10.3390/ijms22031074

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