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Phosphorylation of the HuR ligand APRIL by casein kinase 2 regulates CD83 expression

Jan Chemnitz1, Dorothea Pieper, Cordula Grüttner

  • 1Heinrich-Pette-Institute for Experimental Virology and Immunology, Martinistrasse, Hamburg, Germany. jan.chemnitz@hpi.uni-hamburg.de

European Journal of Immunology
|January 9, 2009
PubMed

Insights

Casein kinase 2 (CK2) regulates CD83 expression by phosphorylating APRIL, a protein crucial for CD83 mRNA transport. Inhibiting CK2 blocks this transport, offering a new strategy to control CD83 levels in activated T cells.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • CD83 is a surface molecule vital for T-cell activation, expressed on mature dendritic cells (DCs) and activated T and B cells.
  • CD83 mRNA nuclear-to-cytoplasmic transport involves HuR, CRM1, and the adaptor protein APRIL (ANP32B).

Purpose of the Study:

  • To investigate the role of casein kinase 2 (CK2) in the regulation of CD83 mRNA nucleocytoplasmic translocation.
  • To identify the specific site of APRIL phosphorylation by CK2 and its functional consequence on CD83 expression.

Main Methods:

  • Utilized CK2-specific inhibitor (4,5,6,7-tetrabromo-2-azabenzimidazole) in activated Jurkat T cells.
  • Performed depletion and knockdown studies targeting CK2 alpha and alpha' subunits.
  • Assessed CD83 mRNA translocation and CD83 protein expression.

Main Results:

  • CK2 phosphorylates APRIL at threonine244 (Thr(244)).
  • CK2 inhibition disrupts CD83 mRNA nucleocytoplasmic translocation and reduces CD83 expression in T cells.
  • The CK2 alpha' subunit is essential for this regulatory mechanism, while the alpha subunit is not.

Conclusions:

  • CK2-mediated phosphorylation of APRIL is a key regulatory step in CD83 mRNA processing and transport.
  • Targeting CK2 provides a novel strategy to modulate CD83 expression, impacting T-cell activation.
  • This study elucidates a complex regulatory pathway for CD83 mRNA, enhancing understanding of immune cell function.

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