| Naslov: | Different glycosylation profiles of cystatin F alter the cytotoxic potential of natural killer cells |
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| Avtorji: | ID Senjor, Emanuela, Institut "Jožef Stefan" (Avtor) ID Pirro, Martina (Avtor) ID Švajger, Urban (Avtor) ID Prunk, Mateja, Institut "Jožef Stefan" (Avtor) ID Sabotič, Jerica, Institut "Jožef Stefan" (Avtor) ID Jewett, Anahid (Avtor) ID Hensbergen, Paul J. (Avtor) ID Perišić, Milica, Institut "Jožef Stefan" (Avtor) ID Kos, Janko, Institut "Jožef Stefan" (Avtor) |
| Datoteke: | PDF - Predstavitvena datoteka, prenos (3,96 MB) MD5: 04686CF42F24E7542363D4B4ED34082F
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| Jezik: | Angleški jezik |
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| Tipologija: | 1.01 - Izvirni znanstveni članek |
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| Organizacija: | IJS - Institut Jožef Stefan
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| Povzetek: | Cystatin F, a cysteine peptidase inhibitor, is a potent modulator of NK cytotoxicity. By inhibiting granule-mediated cytotoxicity pathway, cystatin F induces formation of non-functional NK cell stage, called split-anergy. We show that N-glycosylation determines the localization and cellular function of cystatin F. Cystatin F mostly exhibited high-mannose glycosylation in U-937 cells, both high-mannose and complex glycosylation in NK-92 and primary NKs, and predominantly complex glycosylation in super-charged NKs. Manipulating N-glycosylation with kifunensine increased high-mannose glycosylation of cystatin F and lysosome localisation, which decreased cathepsin C activity and reduced NK cytotoxicity. Mannose-6-phosphate could significantly reduce the internalization of extracellular cystatin F. By comparing NK cells with different cytotoxic potentials, we found that high-mannose cystatin F was strongly associated with lysosomes and cathepsin C in NK-92 cell line. In contrast, in highly cytotoxic super-charged NKs, cystatin F with complex glycosylation was associated with the secretory pathway and less prone to inhibit cathepsin C. Modulating glycosylation to alter cystatin F localisation could increase the cytotoxicity of NK cells, thereby enhancing their therapeutic potential for treating cancer patients. |
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| Ključne besede: | cystatin F, immunosuppression, NK cells, N-Glycosylation |
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| Status publikacije: | Objavljeno |
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| Verzija publikacije: | Objavljena publikacija |
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| Poslano v recenzijo: | 23.05.2023 |
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| Datum sprejetja članka: | 06.11.2023 |
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| Datum objave: | 13.12.2023 |
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| Založnik: | Springer Nature |
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| Leto izida: | 2024 |
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| Št. strani: | 19 str. |
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| Številčenje: | Vol. 81, iss. 1, art. 8 |
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| Izvor: | Švica |
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| PID: | 20.500.12556/DiRROS-23487  |
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| UDK: | 577.27:615.37 |
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| ISSN pri članku: | 1420-9071 |
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| DOI: | 10.1007/s00018-023-05041-x  |
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| COBISS.SI-ID: | 177482499  |
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| Avtorske pravice: | © The Author(s) 2023 |
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| Opomba: | Nasl. z nasl. zaslona;
Opis vira z dne 14.12. 2023;
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| Datum objave v DiRROS: | 04.09.2025 |
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| Število ogledov: | 308 |
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| Število prenosov: | 90 |
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| Metapodatki: |  |
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