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.

Sumoylation of the zinc finger protein ZXDC enhances the function of its transcriptional activation domain

2007 ◽  
Vol 388 (9) ◽  
pp. 965-972 ◽  
Author(s):  
Srikarthika Jambunathan ◽  
Joseph D. Fontes
Keyword(s):  
Zinc Finger ◽  
Transcriptional Activation ◽  
Zinc Finger Protein ◽  
Class Ii ◽  
Activation Domain ◽  
Transcriptional Activation Domain ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Class Ii Mhc ◽  
Important Regulator

Abstract The transcription of major histocompatibility complex class II (MHC II) genes is dependent on the co-activator protein class II trans-activator (CIITA). We have recently identified a protein known as zinc finger X-linked duplicated family member C (ZXDC) that, along with its binding partner ZXDA, forms a complex that interacts with CIITA and regulates MHC II transcription. Western blot analysis with anti-ZXDC antibodies identified two species of the ZXDC protein, one migrating near its predicted molecular mass and one with slower electrophoretic mobility. We report here that the slower migrating form is the result of sumoylation at a single lysine residue within the transcriptional activation domain of ZXDC. Three SUMO proteins (SUMO-1, -2 and -3) can modify the ZXDC protein. Multiple SUMO E3 ligase enzymes and HDAC4 can facilitate ZXDC sumoylation, and one ligase, PIASy, interacts with a specific region of the ZXDC protein. We found that sumoylation does not appear to disrupt or modulate the interaction of ZXDC with its binding partners. Rather, sumoylation of ZXDC is required for full activity of the transcriptional activation domain. Our findings suggest that sumoylation is an important regulator of ZXDC.

scholarly journals Mycobacterium tuberculosisEsxL inhibits MHC-II expression by promoting hypermethylation in class-II transactivator loci in macrophages

2017 ◽  
Vol 292 (17) ◽  
pp. 6855-6868 ◽  
Author(s):  
Srabasti Sengupta ◽  
Saba Naz ◽  
Ishani Das ◽  
Abdul Ahad ◽  
Avinash Padhi ◽  
...  
Keyword(s):  
Class Ii ◽  
Class Ii Transactivator ◽  
Mhc Ii

BLIMP-1 mediates extinction of major histocompatibility class II transactivator expression in plasma cells

10.1038/82788 ◽  
2000 ◽  
Vol 1 (6) ◽  
pp. 526-532 ◽  
Author(s):  
Janet F. Piskurich ◽  
Kuo -I. Lin ◽  
Yi Lin ◽  
Ying Wang ◽  
Jenny P. -Y. Ting ◽  
...  
Keyword(s):  
Plasma Cells ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Class Ii Transactivator ◽  
Major Histocompatibility Class ◽  
Major Histocompatibility Class Ii
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