Inhibition of CD83 cell surface expression during dendritic cell maturation by interference with nuclear export of CD83 mRNA
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...
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| Veröffentlicht in: | The Journal of experimental medicine 2000-05, Vol.191 (9), p.1581-1590 |
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| creator | Kruse, M Rosorius, O Krätzer, F Bevec, D Kuhnt, C Steinkasserer, A Schuler, G Hauber, J |
| description | 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. |
| doi_str_mv | 10.1084/jem.191.9.1581 |
| format | Article |
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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.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>DOI: 10.1084/jem.191.9.1581</identifier><identifier>PMID: 10790432</identifier><language>eng</language><publisher>United States: The Rockefeller University Press</publisher><subject>Antigen Presentation - drug effects ; Antigens, CD ; Biological Transport - drug effects ; CD83 Antigen ; Cell Compartmentation - drug effects ; Cell Differentiation ; Cell Nucleus - metabolism ; Dendritic Cells - cytology ; Dendritic Cells - immunology ; eukaryotic initiation factor eIF-5A ; Eukaryotic Translation Initiation Factor 5A ; Guanine - analogs & derivatives ; Guanine - pharmacology ; Humans ; Immunoglobulins - biosynthesis ; Immunoglobulins - genetics ; Lymphocyte Activation ; Lysine - analogs & derivatives ; Lysine - metabolism ; Membrane Glycoproteins - biosynthesis ; Membrane Glycoproteins - genetics ; N1-^Aguanyl-1,7-diaminoheptane ; Original ; Peptide Initiation Factors - metabolism ; Protein Processing, Post-Translational ; RNA, Messenger - metabolism ; RNA-Binding Proteins ; T-Lymphocytes - immunology ; Up-Regulation</subject><ispartof>The Journal of experimental medicine, 2000-05, Vol.191 (9), p.1581-1590</ispartof><rights>2000 The Rockefeller University Press 2000 The Rockefeller University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c417t-afb7171b5499d3e1178ef674f5bc560ee062eacbcd399fe00b49facde8a814693</citedby><cites>FETCH-LOGICAL-c417t-afb7171b5499d3e1178ef674f5bc560ee062eacbcd399fe00b49facde8a814693</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10790432$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kruse, M</creatorcontrib><creatorcontrib>Rosorius, O</creatorcontrib><creatorcontrib>Krätzer, F</creatorcontrib><creatorcontrib>Bevec, D</creatorcontrib><creatorcontrib>Kuhnt, C</creatorcontrib><creatorcontrib>Steinkasserer, A</creatorcontrib><creatorcontrib>Schuler, G</creatorcontrib><creatorcontrib>Hauber, J</creatorcontrib><title>Inhibition of CD83 cell surface expression during dendritic cell maturation by interference with nuclear export of CD83 mRNA</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>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.</description><subject>Antigen Presentation - drug effects</subject><subject>Antigens, CD</subject><subject>Biological Transport - drug effects</subject><subject>CD83 Antigen</subject><subject>Cell Compartmentation - drug effects</subject><subject>Cell Differentiation</subject><subject>Cell Nucleus - metabolism</subject><subject>Dendritic Cells - cytology</subject><subject>Dendritic Cells - immunology</subject><subject>eukaryotic initiation factor eIF-5A</subject><subject>Eukaryotic Translation Initiation Factor 5A</subject><subject>Guanine - analogs & derivatives</subject><subject>Guanine - pharmacology</subject><subject>Humans</subject><subject>Immunoglobulins - biosynthesis</subject><subject>Immunoglobulins - genetics</subject><subject>Lymphocyte Activation</subject><subject>Lysine - analogs & derivatives</subject><subject>Lysine - metabolism</subject><subject>Membrane Glycoproteins - biosynthesis</subject><subject>Membrane Glycoproteins - genetics</subject><subject>N1-^Aguanyl-1,7-diaminoheptane</subject><subject>Original</subject><subject>Peptide Initiation Factors - metabolism</subject><subject>Protein Processing, Post-Translational</subject><subject>RNA, Messenger - metabolism</subject><subject>RNA-Binding Proteins</subject><subject>T-Lymphocytes - immunology</subject><subject>Up-Regulation</subject><issn>0022-1007</issn><issn>1540-9538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1P3DAQxa2qqGxprxxRTr0leBI7ji-V0FIoEioSas-W44xZo8TZ2gkUiT8eh0UITj3NYX7vzccj5BBoAbRhx7c4FCChkAXwBj6QFXBGc8mr5iNZUVqWOVAq9snnGG8pBcZ4_YnsAxWSsqpckccLv3Gtm9zos9Fm69Omygz2fRbnYLXBDP9tA8a49Ls5OH-Tdei7kBRmBw56moN-NmgfMucnDBYD-qS9d9Mm87PpUYfFaAzT65Dh-tfJF7JndR_x60s9IH_Ofvxe_8wvr84v1ieXuWEgplzbVoCAljMpuwoBRIO2Fszy1vCaItK6RG1a01VSWqS0ZTLt3mGjG2C1rA7I953vdm4H7Az6KehebYMbdHhQo3bqfce7jboZ71RZQsXKJhl8ezEI498Z46QGF5frtcdxjkqkh9ZS_B8EwTnUjCWw2IEmjDEGtK_bAFVLsiolq1KySqol2SQ4envDG3wXZfUEQeGiFw</recordid><startdate>20000501</startdate><enddate>20000501</enddate><creator>Kruse, M</creator><creator>Rosorius, O</creator><creator>Krätzer, F</creator><creator>Bevec, D</creator><creator>Kuhnt, C</creator><creator>Steinkasserer, A</creator><creator>Schuler, G</creator><creator>Hauber, J</creator><general>The Rockefeller University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20000501</creationdate><title>Inhibition of CD83 cell surface expression during dendritic cell maturation by interference with nuclear export of CD83 mRNA</title><author>Kruse, M ; 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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. 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| subjects | Antigen Presentation - drug effects Antigens, CD Biological Transport - drug effects CD83 Antigen Cell Compartmentation - drug effects Cell Differentiation Cell Nucleus - metabolism Dendritic Cells - cytology Dendritic Cells - immunology eukaryotic initiation factor eIF-5A Eukaryotic Translation Initiation Factor 5A Guanine - analogs & derivatives Guanine - pharmacology Humans Immunoglobulins - biosynthesis Immunoglobulins - genetics Lymphocyte Activation Lysine - analogs & derivatives Lysine - metabolism Membrane Glycoproteins - biosynthesis Membrane Glycoproteins - genetics N1-^Aguanyl-1,7-diaminoheptane Original Peptide Initiation Factors - metabolism Protein Processing, Post-Translational RNA, Messenger - metabolism RNA-Binding Proteins T-Lymphocytes - immunology Up-Regulation |
| title | Inhibition of CD83 cell surface expression during dendritic cell maturation by interference with nuclear export of CD83 mRNA |
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