Phosphorylation of the HuR ligand APRIL by casein kinase 2 regulates CD83 expression.
Fully mature DC and, to a lesser extent, activated T and B cells express CD83, a surface molecule that appears to fulfil an important role in efficient T-cell activation. Recently, it has been shown that CD83 mRNA is transported from the nucleus to the cytoplasm by an uncommon route, involving the cellular RNA-binding protein HuR and the nuclear export receptor CRM1. Moreover, the shuttle phosphoprotein APRIL (ANP32B) has been shown to be required for HuR-mediated nucleocytoplasmic translocation of the CD83 mRNA by acting as an adaptor that links HuR and CRM1. Here, we are able to report that casein kinase 2 (CK2) phosphorylates APRIL on residue threonine244 (Thr(244)) and demonstrate that the CK2-specific inhibitor 4,5,6,7-tetrabromo-2-azabenzimidazole abolishes CD83 expression in activated Jurkat T cells by interfering with the nucleocytoplasmic translocation of CD83 mRNA. Depletion and knockdown studies demonstrate that the CK2 alpha' subunit is necessary for this regulation, whereas the CK2 alpha subunit seems to be dispensable. Taken together, the data presented significantly extend our knowledge of the complex regulation of CD83 mRNA processing and provides a novel strategy to interfere with CD83 expression.
Chemnitz
Jan
J
Heinrich-Pette-Institute for Experimental Virology and Immunology, Martinistrasse, Hamburg, Germany. jan.chemnitz@hpi.uni-hamburg.de
Pieper
Dorothea
D
Grüttner
Cordula
C
Hauber
Joachim
J
D000818:Animals; D015703:Antigens, CD / Q000187:drug effects / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045744:Cell Line, Tumor; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005822:Genetic Vectors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007136:Immunoglobulins / Q000187:drug effects / Q000378:metabolism*; D019169:Jurkat Cells; D028884:Karyopherins / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D016601:RNA-Binding Proteins / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014162:Transfection; D014230:Triazoles / Q000494:pharmacology; D000097606:Exportin 1 Protein; D000097802:CD83 Antigen
D015703:Antigens, CD; D000954:Antigens, Surface; D047390:Casein Kinase II; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D007136:Immunoglobulins; D028884:Karyopherins; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014230:Triazoles; D000097606:Exportin 1 Protein; D000097802:CD83 Antigen; C103118:4,5,6,7-tetrabromo-2-azabenzimidazole; C490341:ANP32B protein, human; C098770:ELAVL1 protein, human