Protein kinase C delta is essential to maintain CIITA gene expression in B cells.
Expression of MHC class II genes requires CIITA. Although the transactivation function of CIITA is well characterized, the signaling events that regulate CIITA expression are less understood. In this study, we report that CIITA expression in B cells depends on protein kinase Cdelta (PKCdelta). PKCdelta controls CIITA gene transcription mainly via modulating CREB recruitment to the CIITA promoter without affecting CIITA mRNA stability. Inhibition of PKCdelta by a pharmacological inhibitor or knocking down of endogenous PKCdelta expression by small interfering RNA reduced CREB binding to the CIITA promoter. The decrease of CIITA gene expression in the presence of the PKCdelta inhibitor was prevented by ectopically expressing a constitutively active form of CREB. In addition, histone acetylation of the CIITA promoter is regulated by PKCdelta since the PKCdelta inhibitor treatment or PKCdelta small interfering RNA resulted in decreased histone acetylation. Taken together, our study reveals that PKCdelta is an important signaling molecule necessary to maintain CIITA and MHC class II expression in B cells.
Kwon
Myung-Ja
MJ
Department of Microbiology and Immunology, and Walther Oncology Center, Indiana University School of Medicine, 950 West Walnut Street, Indianapolis, IN 46202, USA.
Soh
Jae-Won
JW
Chang
Cheong-Hee
CH
D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism / Q000502:physiology; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000276:immunology; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D020871:RNA Stability / Q000276:immunology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D015534:Trans-Activators; D051745:Protein Kinase C-delta