Exp Mol Med.
2005 Oct;37(5):466-475.
Menin represses JunD transcriptional activity in protein kinase Ctheta-mediated Nur77 expression
- Affiliations
-
- 1Department of Biochemistry and Molecular Biology, Cancer Research Institute, Korea. hdyoun@snu.ac.kr
- 2Interdisciplinary Program in Genetic Engineering, Seoul National University College of Medicine, 28 Yongon-dong, Chongro-gu, Seoul 110-799, Korea.
- 3College of Pharmacy, Sungkyunkwan University, 300 Chunchun-dong, Suwon 440-746, Korea.
- 4College of Medicine, Sungkyunkwan University, 300 Chunchun-dong, Suwon 440-746, Korea.
Abstract
- 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 PKC theta targets AP-1 like response element in the Nur77 promoter where JunD constitutively binds. PKC theta 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 PKC theta/ p300-mediated transcriptional activity of JunD in T cell. Its dynamic regulation of histone modifiers with JunD is responsible for PKCq-synergistic effect on Nur77 expression in T cell.
MeSH Terms
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Cell Line, Tumor
DNA-Binding Proteins/*genetics
Enzyme Activation
*Gene Expression Regulation
Humans
Isoenzymes/*metabolism
Mitogen-Activated Protein Kinases/metabolism
*Multiple Endocrine Neoplasia Type 1
Promoter Regions (Genetics)/genetics
Protein Kinase C/*metabolism
Proto-Oncogene Proteins/genetics/*metabolism
Proto-Oncogene Proteins c-jun/*antagonists & inhibitors/metabolism
Receptors, Cytoplasmic and Nuclear/*genetics
Receptors, Steroid/*genetics
Research Support, Non-U.S. Gov't
Response Elements
Transcription Factors/*genetics
Transcription, Genetic/*genetics
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