Fernández Messina, Lola MaríaReyburn, HughValés‐Gómez, Mar2024-01-312024-01-312016Fernández‐Messina, Lola, et al. «A Short Half‐life of ULBP1 at the Cell Surface Due to Internalization and Proteosomal Degradation». Immunology & Cell Biology, vol. 94, n.o 5, mayo de 2016, pp. 479-85. https://doi.org/10.1038/icb.2016.2.0818-964110.1038/icb.2016.2https://hdl.handle.net/20.500.14352/97130ACKNOWLEDGEMENTS We thank members from the HT Reyburn and MV-G laboratories for helpful discussions, and Prof Jack L Strominger for the kind gift of reagents. This work was supported by grants from Fondo de Investigación Sanitaria (PI11/00298][PS09/00181), from the Spanish Ministry of Economy and Competitivity (MINECO) (SAF2012–32293) and from the Regional Government of Madrid (grant number S2010/BMD-2326 INMUNOTHERCAN). LFM is currently supported by a Juan de la Cierva grant (Spanish Ministry of Economy and Competitivity).The expression of NKG2D ligands (NKG2D-L) flag stressed cells for immune recognition and destruction. A precise control of the cell surface expression of these proteins is therefore required to ensure an appropriate immune response and it is becoming clear that NKG2D ligand expression is regulated at multiple levels. We now report that the surface stability of the human glycosyl-phosphatidyl-inositol (GPI)-anchored ligand ULBP1 (UL16-binding protein) at the plasma membrane is lower than other ULBP molecules. This difference in stability is due neither to shedding nor to a higher internalization rate of ULBP1 but rather occurs because of a rapid degradation of ULBP1 protein after internalization from the cell surface that is blocked by proteasome inhibition. These data indicate that, in addition to the known transcriptional and post-translational mechanisms, surface expression of human NKG2D-L is also regulated by protein turnover and that the brief residence of ULBP1 could contribute to the fine tuning of immune responses.engA short half‐life of ULBP1 at the cell surface due to internalization and proteosomal degradationjournal article1440-1711https://doi.org/10.1038/icb.2016.2restricted access577.27ULBP1NKG2D-ligandsproteasomeNK cellsBiología celular (Biología)Bioquímica (Biología)Inmunología2407 Biología Celular2403 Bioquímica2412 Inmunología