title: A short half-life of ULBP1 at the cell surface due to internalization and proteosomal degradation.
abstract: 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.
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Madrid, Spain.
authors.forename: Lola
authors.initials: L
authors.lastname: Fernández-Messina
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Madrid, Spain.
authors.forename: Hugh T
authors.initials: HT
authors.lastname: Reyburn
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Madrid, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Valés-Gómez
mesh_terms: D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D004705:Endocytosis / Q000187:drug effects; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006207:Half-Life; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000494:pharmacology; D055550:Protein Stability / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects
chemical_list: D017261:Glycosylphosphatidylinositols; D047908:Intracellular Signaling Peptides and Proteins; D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex