title: Post-transcriptional regulation of CD83 expression by AUF1 proteins.
abstract: Mature dendritic cells (DC), activated lymphocytes, mononuclear cells and neutrophils express CD83, a surface protein apparently necessary for effective DC-mediated activation of naïve T-cells and T-helper cells, thymic T-cell maturation and the regulation of B-cell activation and homeostasis. Although a defined ligand of CD83 remains elusive, the multiple cellular subsets expressing CD83, as well as its numerous potential implications in immunological processes suggest that CD83 plays an important regulatory role in the mammalian immune system. Lately, nucleocytoplasmic translocation of CD83 mRNA was shown to be mediated by direct interaction between the shuttle protein HuR and a novel post-transcriptional regulatory element (PRE) located in the CD83 transcript's coding region. Interestingly, this interaction commits the CD83 mRNA to efficient nuclear export through the CRM1 protein translocation pathway. More recently, the cellular phosphoprotein and HuR ligand ANP32B (APRIL) was demonstrated to be directly involved in this intracellular transport process by linking the CD83 mRNA:HuR ribonucleoprotein (RNP) complex with the CRM1 export receptor. Casein kinase II regulates this process by phosphorylating ANP32B. Here, we identify another RNA binding protein, AUF1 (hnRNP D) that directly interacts with CD83 PRE. Unlike HuR:PRE binding, this interaction has no impact on intracellular trafficking of CD83 mRNA-containing complexes; but it does regulate translation of CD83 mRNA. Thus, our data shed more light on the complex process of post-transcriptional regulation of CD83 expression. Interfering with this process may provide a novel strategy for inhibiting CD83, and thereby cellular immune activation.
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistrasse 52, D-20251 Hamburg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Ehlers
authors.forename: Susann
authors.initials: S
authors.lastname: Schirmer
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Kehlenbach
authors.forename: Joachim
authors.initials: J
authors.lastname: Hauber
authors.forename: Jan
authors.initials: J
authors.lastname: Chemnitz
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis; D020033:Protein Isoforms / Q000378:metabolism; D034622:RNA Interference; D038621:Regulatory Sequences, Ribonucleic Acid; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D020033:Protein Isoforms; D038621:Regulatory Sequences, Ribonucleic Acid; D000097802:CD83 Antigen; C000630986:HNRNPD protein, human