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

2021 ◽  
Vol 22 (3) ◽  
pp. 1074
Author(s):  
Jorge Alfonso León Machado ◽  
Viktor Steimle
Keyword(s):  
Gene Expression ◽  
Mhc Class Ii ◽  
Protein Interactions ◽  
Transcriptional Regulator ◽  
Class Ii ◽  
Class Ii Transactivator ◽  
Mhc I ◽  
Mhc Ii ◽  
Mhc Class Ii Transactivator

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.

scholarly journals CIITA is a transcriptional coactivator that is recruited to MHC class II promoters by multiple synergistic interactions with an enhanceosome complex

2000 ◽  
Vol 14 (9) ◽  
pp. 1156-1166
Author(s):  
Krzysztof Masternak ◽  
Annick Muhlethaler-Mottet ◽  
Jean Villard ◽  
Madeleine Zufferey ◽  
Viktor Steimle ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Protein Interactions ◽  
Class Ii ◽  
Hereditary Disease ◽  
Transcriptional Coactivator ◽  
Protein Protein Interactions ◽  
Mhc I ◽  
Mhc Ii ◽  
Class Ii Mhc

By virtue of its control over major histocompatibility complex class II (MHC-II) gene expression, CIITA represents a key molecule in the regulation of adaptive immune responses. It was first identified as a factor that is defective in MHC-II deficiency, a hereditary disease characterized by the absence of MHC-II expression. CIITA is a highly regulated transactivator that governs all spatial, temporal, and quantitative aspects of MHC-II expression. It has been proposed to act as a non-DNA-binding transcriptional coactivator, but evidence that it actually functions at the level of MHC-II promoters was lacking. By means of chromatin immunoprecipitation assays, we show here for the first time that CIITA is physically associated with MHC-II, as well asHLA–DM, Ii, MHC-I, and β2mpromoters in vivo. To dissect the mechanism by which CIITA is recruited to the promoter, we have developed a DNA-dependent coimmunoprecipitation assay and a pull-down assay using immobilized promoter templates. We demonstrate that CIITA recruitment depends on multiple, synergistic protein–protein interactions with DNA-bound factors constituting the MHC-II enhanceosome. CIITA therefore represents a paradigm for a novel type of regulatory and gene-specific transcriptional cofactor.

scholarly journals The MHC class?II transactivator (CIITA) mRNA stability is critical for the HLA class?II gene expression in myelomonocytic cells

2005 ◽  
Vol 35 (2) ◽  
pp. 603-611 ◽  
Author(s):  
Andrea De Lerma Barbaro ◽  
Francesco?A. Procopio ◽  
Lorenzo Mortara ◽  
Giovanna Tosi ◽  
Roberto?S. Accolla
Keyword(s):  
Gene Expression ◽  
Mhc Class Ii ◽  
Mrna Stability ◽  
Class Ii ◽  
Hla Class Ii ◽  
Class Ii Transactivator ◽  
Myelomonocytic Cells ◽  
Mhc Class Ii Transactivator

scholarly journals Class II transactivator regulates the expression of multiple genes involved in antigen presentation.

1995 ◽  
Vol 181 (2) ◽  
pp. 765-767 ◽  
Author(s):  
C H Chang ◽  
R A Flavell
Keyword(s):  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Class Ii Transactivator ◽  
Leukocyte Antigen ◽  
Expression Of Genes ◽  
Mhc Class Ii Transactivator ◽  
Mutant Cells ◽  
Mhc Class Ii Genes

CIITA (a major histocompatibility complex [MHC] class II transactivator) has been shown to be required for the expression of MHC class II genes in both B cells and interferon gamma-inducible cells. Here we demonstrate that CIITA not only activates MHC class II genes but also genes required for antigen presentation. Mutant HeLa cells, defective in the expression of classic MHC class II genes, invariant chain, and the newly described human histocompatibility leukocyte antigen-DM genes, were used to study the role of CIITA in the regulation of these genes. Upon transfection with CIITA cDNA, the mutant cells expressed all three genes, suggesting that CIITA is a global regulator for the expression of genes involved in antigen presentation.

scholarly journals The MHC Class II transactivator CIITA inhibits the persistent activation of NF-kB by Tax-1

Retrovirology ◽  
2015 ◽  
Vol 12 (S1) ◽  
Author(s):  
Greta Forlani ◽  
Rawan Abdallah ◽  
Luisa Guidali ◽  
Roberto S Accolla ◽  
Giovanna Tosi
Keyword(s):  
Mhc Class Ii ◽  
Class Ii ◽  
Class Ii Transactivator ◽  
Mhc Class Ii Transactivator
Sign in / Sign up

Export Citation Format

Share Document