PMID- 10790432 OWN - NLM STAT- MEDLINE DCOM- 20000530 LR - 20231213 IS - 0022-1007 (Print) IS - 1540-9538 (Electronic) IS - 0022-1007 (Linking) VI - 191 IP - 9 DP - 2000 May 1 TI - Inhibition of CD83 cell surface expression during dendritic cell maturation by interference with nuclear export of CD83 mRNA. PG - 1581-90 AB - Dendritic cells (DCs), nature's adjuvant, must mature to sensitize T cells. However, although the maturation process is essential, it is not yet fully understood at the molecular level. In this study, we investigated the course of expression of the unique hypusine-containing protein eukaryotic initiation factor 5A (eIF-5A), which is part of a particular RNA nuclear export pathway, during in vitro generation of human DCs. We show that eIF-5A expression is significantly upregulated during DC maturation. Furthermore, an inhibitor of the hypusine modification, GC7 (N(1)-guanyl-1, 7-diaminoheptane), prevents CD83 surface expression by apparently interfering with nucleocytoplasmic translocation of the CD83 mRNA and, importantly, significantly inhibits DC-mediated T lymphocyte activation. The data presented suggest that CD83 mRNA is transported from the nucleus to the cytoplasm via a specific nuclear export pathway and that hypusine formation appears to be essential for the maturation of functional DCs. Therefore, pharmacological interference with hypusine formation may provide a new possibility to modulate DC function. FAU - Kruse, M AU - Kruse M AD - Department of Dermatology, University Erlangen-Nurnberg, D-91054 Erlangen, Germany. FAU - Rosorius, O AU - Rosorius O FAU - Kratzer, F AU - Kratzer F FAU - Bevec, D AU - Bevec D FAU - Kuhnt, C AU - Kuhnt C FAU - Steinkasserer, A AU - Steinkasserer A FAU - Schuler, G AU - Schuler G FAU - Hauber, J AU - Hauber J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (Antigens, CD) RN - 0 (Immunoglobulins) RN - 0 (Membrane Glycoproteins) RN - 0 (N(1)-guanyl-1,7-diaminoheptane) RN - 0 (Peptide Initiation Factors) RN - 0 (RNA, Messenger) RN - 0 (RNA-Binding Proteins) RN - 3874VXF092 (hypusine) RN - 5Z93L87A1R (Guanine) RN - K3Z4F929H6 (Lysine) SB - IM MH - Antigen Presentation/drug effects MH - Antigens, CD MH - Biological Transport/drug effects MH - Cell Compartmentation/drug effects MH - Cell Differentiation MH - Cell Nucleus/*metabolism MH - Dendritic Cells/*cytology/immunology MH - Guanine/analogs & derivatives/pharmacology MH - Humans MH - Immunoglobulins/*biosynthesis/genetics MH - Lymphocyte Activation MH - Lysine/*analogs & derivatives/metabolism MH - Membrane Glycoproteins/*biosynthesis/genetics MH - Peptide Initiation Factors/*metabolism MH - Protein Processing, Post-Translational MH - RNA, Messenger/*metabolism MH - *RNA-Binding Proteins MH - T-Lymphocytes/immunology MH - Up-Regulation MH - Eukaryotic Translation Initiation Factor 5A MH - CD83 Antigen PMC - PMC2213428 EDAT- 2000/05/03 09:00 MHDA- 2000/06/03 09:00 PMCR- 2000/11/01 CRDT- 2000/05/03 09:00 PHST- 2000/05/03 09:00 [pubmed] PHST- 2000/06/03 09:00 [medline] PHST- 2000/05/03 09:00 [entrez] PHST- 2000/11/01 00:00 [pmc-release] AID - 991614 [pii] AID - 10.1084/jem.191.9.1581 [doi] PST - ppublish SO - J Exp Med. 2000 May 1;191(9):1581-90. doi: 10.1084/jem.191.9.1581.