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Publication : Role of PKCdelta in IFN-gamma-inducible CIITA gene expression.

First Author  Kwon MJ Year  2007
Journal  Mol Immunol Volume  44
Issue  11 Pages  2841-9
PubMed ID  17346795 Mgi Jnum  J:120075
Mgi Id  MGI:3703831 Doi  10.1016/j.molimm.2007.01.035
Citation  Kwon MJ, et al. (2007) Role of PKCdelta in IFN-gamma-inducible CIITA gene expression. Mol Immunol 44(11):2841-9
abstractText  The class II transactivator (CIITA) is a key regulatory factor for MHC class II expression. Here, we demonstrate that PKCdelta plays an important role in regulating IFN-gamma-inducible CIITA gene expression in macrophages. Inhibition of PKCdelta by either a PKCdelta inhibitor or a dominant negative (DN) mutant form of PKCdelta led to down-regulation of CIITA expression. The decrease in CIITA expression by PKCdelta inhibition was in part due to the reduced recruitment of serine 727-phosphorylated Stat1 and histone acetyltransferases to the CIITA promoter. As a result, IFN-gamma induced histone acetylation at the CIITA promoter is also compromised. However, inhibition of PKCdelta did not affect IRF-1 expression or IRF-1 binding to the CIITA promoter. Therefore, we report, for the first time, that PKCdelta is an essential signaling molecule to achieve the maximal expression of CIITA in response to IFN-gamma in macrophages. In addition, although IRF-1 is a key transcription factor to activate the IFN-gamma inducible CIITA promoter, the effect of PKCdelta on CIITA expression is mediated primarily by serine phosphorylation of Stat 1.
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