Menin represses JunD transcriptional activity in protein kinase C theta-mediated Nur77 expression.
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 PKCtheta targets AP-1 like response element in the Nur77 promoter where JunD constitutively binds. PKCtheta 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 PKCtheta/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.
Kim
Hyungsoo
H
Department of Biochemistry and Molecular Biology, Cancer Research Institute, Seoul National University, College of Medicine, 28 Yongon-dong, Chongro-gu, Seoul 110-799, Korea.
Lee
Ji Eun
JE
Kim
Bu Yeon
BY
Cho
Eun Jung
EJ
Kim
Seong Tae
ST
Youn
Hong Duk
HD
D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics*; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018761:Multiple Endocrine Neoplasia Type 1; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D011401:Promoter Regions, Genetic / Q000235:genetics; D011493:Protein Kinase C / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D011987:Receptors, Steroid / Q000235:genetics*; D020218:Response Elements; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*
D004268:DNA-Binding Proteins; D007527:Isoenzymes; C539821:NR4A1 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D020928:Mitogen-Activated Protein Kinases