Fernández-Messina Lola, Reyburn Hugh T, Valés-Gómez Mar
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Madrid, Spain.
Immunol Cell Biol. 2016 May;94(5):479-85. doi: 10.1038/icb.2016.2. Epub 2016 Jan 6.
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.
NKG2D配体（NKG2D-L）的表达标记应激细胞以供免疫识别和破坏。因此，需要精确控制这些蛋白质的细胞表面表达以确保适当的免疫反应，并且越来越清楚的是，NKG2D配体表达在多个水平受到调节。我们现在报告，人糖基磷脂酰肌醇（GPI）锚定配体ULBP1（UL16结合蛋白）在质膜上的表面稳定性低于其他ULBP分子。这种稳定性差异既不是由于脱落也不是由于ULBP1的内化率更高，而是由于从细胞表面内化后ULBP1蛋白的快速降解，而蛋白酶体抑制可阻止这种降解。这些数据表明，除了已知的转录和翻译后机制外，人NKG2D-L的表面表达也受蛋白质周转调节，并且ULBP1的短暂驻留可能有助于免疫反应的微调。
