scholarly journals Regulating the Activity of Class II Transactivator by Posttranslational Modifications: Exploring the Possibilities

2009 ◽  
Vol 29 (21) ◽  
pp. 5639-5644 ◽  
Author(s):  
Xiaoyan Wu ◽  
Xiaocen Kong ◽  
Larry Luchsinger ◽  
Barbara D. Smith ◽  
Yong Xu
Keyword(s):  
Posttranslational Modifications ◽  
Posttranslational Modification ◽  
Transcriptional Activity ◽  
Class Ii ◽  
Environmental Cues ◽  
Amino Acid Residues ◽  
Class Ii Transactivator ◽  
Histocompatibility Complex ◽  
Spatiotemporal Control ◽  
Fine Tune

ABSTRACT First identified as the master regulator of major histocompatibility complex II transcription, class II transactivator (CIITA) has since been implicated in a host of pathologies by modulating the transcription of multiple different genes. How CIITA caters to cell- and tissue-specific transcriptional needs is hotly debated and investigated. One of the possible mechanisms underlying spatiotemporal control of CIITA transcriptional activity is the posttranslational modification (PTM) machinery that refines certain amino acid residues of CIITA and hence alters its activity in response to specific cellular and environmental cues. This review discusses our current understanding of the PTM map of CIITA, how these modifications fine-tune its activity, and how the study of this area may lead to potential therapeutic strategies.

scholarly journals 15es JSFM : Prix Master 2017

2018 ◽  
Vol 34 ◽  
pp. 35-38
Author(s):  
Cyrielle Hou ◽  
Yasmine Baba-Amer ◽  
Maximilien Bencze ◽  
Frédéric Relaix ◽  
François Jérôme Authier
Keyword(s):  
Major Histocompatibility Complex ◽  
Nous Avons ◽  
Major Histocompatibility Complex Class ◽  
Class Ii ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Class Ii Transactivator ◽  
Histocompatibility Complex

Les myopathies inflammatoires et dysimmunitaires (DIMs) touchent 14/100 000 personnes dans le monde. Ces pathologies sont classées par des critères immunopathologiques en quatre groupes : (1) polymyosites (PM)/ myosites à inclusions (IBM), (2) dermatomyosites, (3) myopathies nécrosantes auto-immunes et (4) myosites de chevauchement comprenant le syndrome anti-synthétase (ASS). Les ASS et PM/IBM sont caractérisées par la présence d’infiltrats inflammatoires mononucléés. Récemment, nous avons mis en évidence une expression myocytaire du complexe majeur d’histocompatibilité de type 2 (CMH2) dans les muscles de patients atteints d’ASS et d’IBM. L’expression du CMH2 est connue pour être induite par l’interféron-gamma (IFNγ) dans les cellules myogéniques. Or, les lymphocytes T CD8 (LTCD8), cellules productrices d’IFNγ sont retrouvés à proximité des fibres musculaires CMH2 positives. Cette cytokine inhibe la différenciation musculaire in vitro par l’interaction CIITA-myogénine (CIITA : major histocompatibility complex class II transactivator). Les mécanismes impliquant une toxicité musculaire médiée par les lymphocytes dans les DIMs restent inconnus. Les objectifs de ce projet sont dans un premier temps de caractériser les effets de l’IFNγ sur la biologie des cellules musculaires par des approches morphologiques, moléculaires et cellulaires. Puis, d’identifier le rôle de l’IFNγ dans ces myopathies et son impact au cours de la régénération musculaire. Des études préliminaires in vitro ont été réalisées sur des myoblastes humains et murins exposés ou non à l’IFNγ. Nos résultats devraient permettre d’obtenir de meilleures connaissances sur la physiopathologie des DIMs et d’identifier de potentielles nouvelles cibles thérapeutiques.

scholarly journals N-terminal destruction signals lead to rapid degradation of the major histocompatibility complex class II transactivator CIITA

2003 ◽  
Vol 33 (8) ◽  
pp. 2337-2347 ◽  
Author(s):  
Felix Schnappauf ◽  
Sandra B. Hake ◽  
Margarita M. Camacho Carvajal ◽  
Séverine Bontron ◽  
Barbara Lisowska-Grospierre ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Class Ii ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Class Ii Transactivator ◽  
Rapid Degradation ◽  
Histocompatibility Complex

scholarly journals Pulling a Ligase out of a “HAT”: pCAF Mediates Ubiquitination of the Class II Transactivator

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Julie E. Morgan ◽  
Susanna F. Greer
Keyword(s):  
Posttranslational Modifications ◽  
Histone Acetyltransferase ◽  
E3 Ligase ◽  
Class Ii ◽  
Nuclear Region ◽  
Class Ii Transactivator ◽  
Mhc Ii ◽  
Major Histocompatibility Class Ii ◽  
Class Ii Mhc ◽  
Cellular Movement

The Class II Transactivator (CIITA) is essential to the regulation of Major Histocompatibility Class II (MHC II) genes transcription. As the “master regulator” of MHC II transcription, CIITA regulation is imperative and requires various posttranslational modifications (PTMs) in order to facilitate its role. Previously we identified various ubiquitination events on CIITA. Monoubiquitination is important for CIITA transactivity, while K63 linked ubiquitination is involved in crosstalk with ERK1/2 phosphorylation, where together they mediate cellular movement from the cytoplasm to nuclear region. Further, CIITA is also modified by degradative K48 polyubiquitination. However, the E3 ligase responsible for these modifications was unknown. We show CIITA ubiquitination and transactivity are enhanced with the histone acetyltransferase (HAT), p300/CBP associated factor (pCAF), and the E3 ligase region within pCAF is necessary for both. Additionally, pCAF mediated ubiquitination is independent of pCAF’s HAT domain, and acetylation deficient CIITA is K48 polyubiquitinated and degraded in the presence of pCAF. Lastly, we identify the histone acetyltransferase, pCAF, as the E3 ligase responsible for CIITA’s ubiquitination.

scholarly journals 17β-Estradiol Inhibits Class II Major Histocompatibility Complex (MHC) Expression: Influence on Histone Modifications and CBP Recruitment to the Class II MHC Promoter

2004 ◽  
Vol 18 (8) ◽  
pp. 1963-1974 ◽  
Author(s):  
Jill Adamski ◽  
Zhendong Ma ◽  
Susan Nozell ◽  
Etty N. Benveniste
Keyword(s):  
Major Histocompatibility Complex ◽  
Histone Acetylation ◽  
Binding Protein ◽  
Class Ii ◽  
Interferon Γ ◽  
Class Ii Transactivator ◽  
Protein Levels ◽  
Histocompatibility Complex ◽  
Class Ii Mhc ◽  
17Β Estradiol

Abstract Major histocompatibility complex (MHC) class II proteins are important for the initiation of immune responses and are essential for specific recognition of foreign antigens by the immune system. Regulation of class II MHC expression primarily occurs at the transcriptional level. The class II transactivator protein is the master regulator that is essential for both constitutive and interferon-γ-inducible class II MHC expression. Estrogen [17β-estradiol (17β-E2)] has been shown to have immunomodulatory effects. In this study, we show that 17β-E2 down-regulates interferon-γ inducible class II MHC protein levels on brain endothelial cells, as well as other cell types (astrocytes, fibrosacroma cells, macrophages). The inhibitory effects of 17β-E2 on class II MHC expression are not due to changes in class II transactivator mRNA or protein levels, rather, 17β-E2 mediates inhibition at the level of class II MHC gene expression. We demonstrate that 17β-E2 attenuates H3 and H4 histone acetylation and cAMP response element binding protein-binding protein association with the class II MHC promoter, suggesting that 17β-E2 inhibits class II MHC expression by a novel mechanism involving modification of the histone acetylation status of the class II MHC promoter.

scholarly journals Interferon (IFN) beta acts downstream of IFN-gamma-induced class II transactivator messenger RNA accumulation to block major histocompatibility complex class II gene expression and requires the 48-kD DNA-binding protein, ISGF3-gamma.

1995 ◽  
Vol 182 (5) ◽  
pp. 1517-1525 ◽  
Author(s):  
H T Lu ◽  
J L Riley ◽  
G T Babcock ◽  
M Huston ◽  
G R Stark ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Messenger Rna ◽  
Class Ii ◽  
Type I ◽  
Major Histocompatibility ◽  
Mrna Accumulation ◽  
Class Ii Transactivator ◽  
Ifn Gamma ◽  
Histocompatibility Complex

Interferon (IFN) gamma, a cardinal proinflammatory cytokine, induces expression of the gene products of the class II locus of the major histocompatibility complex (MHC), whereas IFN-alpha or -beta suppresses MHC class II expression. The mechanism of IFN-beta-mediated MHC class II inhibition has been unclear. Recently, a novel factor termed class II transactivator (CIITA) has been identified as essential for IFN-gamma-induced MHC class II transcription. We studied the status of IFN-gamma-induced CIITA messenger RNA (mRNA) accumulation and CIITA-driven transactivation in IFN-beta-treated cells and used cell lines that had defined defects in the type I IFN response pathway to address the roles of IFN signaling components in the inhibition of MHC class II induction. IFN-beta treatment did not suppress IFN-gamma-induced accumulation of CIITA mRNA. After cells were stably transfected with CIITA, endogenous MHC class II genes were constitutively expressed, and MHC class II promoters, delivered by transfection, were actively transcribed in CIITA-expressing cells. Expression of these promoters was significantly impaired by pretreatment with IFN-beta. These results suggest that IFN-beta acts downstream of CIITA mRNA accumulation, and acts in part by reducing the functional competence of CIITA for transactivating MHC class II promoters. IFN stimulated gene factor 3 (ISGF3) gamma was essential for IFN-beta to mediate inhibition of MHC class II induction, regardless of whether MHC class II transcription was stimulated by IFN-gamma or directly by CIITA expression. Results of these experiments suggest that inhibition of MHC class II in IFN-beta-treated cells requires expression of gene(s) directed by the ISGF3-IFN-stimulated response element pathway, and that these gene product(s) may act by blocking CIITA-driven transcription of MHC class II promoters.

scholarly journals TLRs in the Gut I. The role of TLRs/Nods in intestinal development and homeostasis

2007 ◽  
Vol 292 (1) ◽  
pp. G6-G10 ◽  
Author(s):  
Ian R. Sanderson ◽  
W. Allan Walker
Keyword(s):  
Immune System ◽  
Family Members ◽  
Adaptive Immune System ◽  
Class Ii ◽  
Intestinal Development ◽  
Developmentally Regulated ◽  
Class Ii Transactivator ◽  
Adaptive Immune ◽  
Histocompatibility Complex

The innate immune system includes microbial pattern recognition receptors that detect bacteria and viral products at the cell surface, in vesicles, and within the cytoplasm. Transmembrane signaling occurs through Toll-like receptors (TLRs). Cytoplasmic receptors are generally members of the nucleotide-binding domain (NOD)-leucine-rich repeat (LRR) family (CATERPILLER family). They influence the effects of other family members and of TLRs. Most NOD-LRR members enhance signal transduction, but Monarch-1 counterbalances TLR activity. NOD-LRR family members also act within the adaptive immune system. The class II transactivator regulates major histocompatibility complex class II expression. In the intestine, it is developmentally regulated, and its expression depends on weaning and, independently, on age.

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