Menin represses JunD transcriptional activity in protein kinase C[theta]-mediated Nur77 expression

• Published in: Experimental & molecular medicine Vol. 37; no. 5; pp. 466 - 475
• Main Authors: Kim, Hyungsoo, Lee, Ji-eun, Kim, Bu-yeon, Cho, Eun-jung, Kim, Seong-tae, Youn, Hong-duk
• Format: Journal Article
• Language: English
• Published: Seoul Springer Nature B.V 01.10.2005; 생화학분자생물학회
• Subjects: 생화학
• ISSN: 1226-3613; 2092-6413
• DOI: 10.1038/emm.2005.57

TCR signaling leading to thymocyte apoptosis is mediated through the expression of the Nur77 family of orphan nuclear receptors. It has been shown that the Nur77 promoter is activated by at least two signaling pathways, one mediated by calcium and the other by protein kinase C (PKC). MEF2D has been known to regulate Nur77 expression in a calcium- dependent manner. The mechanism by which calcium regulates MEF2D is through dissociation of calcium-sensitive MEF2 corepressors (Cabin1/ HDACs, HDAC4/5) and the association with calcineurin-activated transcription factor NF-AT and the coactivator p300. However, little is known about how PKC activates the Nur77 promoter. Herein, we report that PKCθ targets AP-1 like response element in the Nur77 promoter where JunD constitutively binds. PKCθ triggers mitogen-activated protein kinase- inediated phosphorylation of JunD, and increases transcriptional activity of JunD, cooperatively with p300. Menin is identified as the transcriptional corepressor for JunD via recruitment of mSin3-istone deacetylases. In fact, Menin represses PKCθ/ p300-mediated transcriptional activity of JunD in T cell. Its dynamic regulation of histone modifiers with JunD is responsible for PKCθ-synergistic effect on Nur77 expression in T cell.