The class II transactivator (CIITA) is a potent and critical transcriptional regulator. It activates genes necessary for antigen presentation function. It also regulates cytokine gene expression in CD4 T cells. We recently found that CIITA prevents cell death by inhibiting Fas ligand (FasL) gene expression. Thus, CIITA regulates multiple immune responses. The activation and the repression function of CIITA are mediated by its interaction with other transcription factors. To activate the target gene, CIITA interacts with DNA binding proteins and recruits the coactivator CBP/p300 to the promoter forming an enhanceosome necessary for transcription. In addition, CIITA interacts with self. Inter- and intramolecular interactions of CIITA are essential for transactivation function. Each domain of CIITA has a distinct role and all domains are required for CIITA activity. However, the regulatory mechanisms of CIITA interaction with self and other proteins are poorly understood and remain to be investigated.
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http://dx.doi.org/10.1385/IR:25:2:131 | DOI Listing |
J Clin Invest
January 2025
Department of Biochemistry and Molecular Genetics and.
Mutations or homozygous deletions of MHC class II (MHC-II) genes are commonly found in B cell lymphomas that develop in immune-privileged sites and have been associated with patient survival. However, the mechanisms regulating MHC-II expression, particularly through genetic and epigenetic factors, are not yet fully understood. In this study, we identified a key signaling pathway involving the histone H2AK119 deubiquitinase BRCA1 associated protein 1 (BAP1), the interferon regulatory factor interferon regulatory factor 1 (IRF1), and the MHC-II transactivator class II transactivator (CIITA), which directly activates MHC-II gene expression.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Center for Nutritional Sciences, Food Science and Human Nutrition Department, College of Agricultural and Life Sciences, University of Florida, Gainesville, FL 32611.
Documented worldwide, impaired immunity is a cardinal signature resulting from loss of dietary zinc, an essential micronutrient. A steady supply of zinc to meet cellular requirements is regulated by an array of zinc transporters. Deletion of the transporter Zip14 (Slc39a14) in mice produced intestinal inflammation.
View Article and Find Full Text PDFUnlabelled: Regulatory T cells (T cells) play a critical role in suppressing anti-tumor immunity, often resulting in unfavorable clinical outcomes across numerous cancers. However, systemic T depletion, while augmenting anti-tumor responses, also triggers detrimental autoimmune disorders. Thus, dissecting the mechanisms by which T cells navigate and exert their functions within the tumor microenvironment (TME) is pivotal for devising innovative T -centric cancer therapies.
View Article and Find Full Text PDFHaematologica
December 2024
Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen.
Arthritis Rheumatol
December 2024
Institute for Clinical and Translational Research, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
Objective: Idiopathic inflammatory myopathies (myositis, IIMs) are rare, systemic autoimmune disorders that lead to muscle inflammation, weakness, and extra-muscular manifestations, with a strong genetic component influencing disease development and progression. Previous genome-wide association studies identified loci associated with IIMs. In this study, we imputed data from two prior genome-wide myositis studies and analyzed the largest myositis dataset to date to identify novel risk loci and susceptibility genes associated with IIMs and its clinical subtypes.
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