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

Hyungsoo Kim1, Ji Eun Lee, Bu Yeon Kim

  • 1Department of Biochemistry and Molecular Biology, Cancer Research Institute, Seoul National University, College of Medicine, 28 Yongon-dong, Chongro-gu, Seoul 110-799, Korea.

Experimental & Molecular Medicine
|November 3, 2005
PubMed

Insights

Protein kinase C (PKC) activates Nur77 expression via JunD phosphorylation and coactivation with p300. Menin represses this pathway, highlighting its role in T cell signaling and Nur77 regulation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • T-cell receptor (TCR) signaling induces thymocyte apoptosis through Nur77 orphan nuclear receptor expression.
  • Nur77 promoter activation involves calcium and protein kinase C (PKC) pathways.
  • MEF2D regulates Nur77 via calcium-dependent mechanisms involving corepressors and transcription factors.

Purpose of the Study:

  • To elucidate the mechanism by which PKC activates the Nur77 promoter.
  • To identify key regulatory proteins and interactions in the PKC-mediated Nur77 activation pathway.

Main Methods:

  • Investigated the role of PKCtheta in targeting the AP-1 response element of the Nur77 promoter.
  • Analyzed JunD phosphorylation and transcriptional activity mediated by PKCtheta and p300.
  • Identified Menin as a transcriptional corepressor for JunD, involving mSin3-histone deacetylases.

Main Results:

  • PKCtheta targets the AP-1 site on the Nur77 promoter, where JunD binds constitutively.
  • PKCtheta-mediated phosphorylation of JunD enhances its transcriptional activity, cooperatively with p300.
  • Menin acts as a corepressor for JunD, recruited by mSin3-histone deacetylases, and represses PKCtheta/p300 activity in T cells.

Conclusions:

  • PKCtheta activates Nur77 expression through JunD phosphorylation and p300 coactivation.
  • Menin's dynamic regulation of histone modifiers with JunD is crucial for the synergistic effect of PKCtheta on Nur77 expression in T cells.

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