Regulation of NKG2D-ligand cell surface expression by intracellular calcium after HDAC-inhibitor treatment
Research output: Contribution to journal › Journal article › Research › peer-review
In this study we demonstrate that histone deacetylase (HDAC)-inhibitor mediated cell surface expression of the structural different NKG2D-ligands MICA/B and ULBP2 is calcium-dependent. Treatment with the calcium chelator EGTA inhibited constitutive as well as HDAC-inhibitor induced MICA/B and ULBP2 cell surface expression on melanoma cells and Jurkat T-cells. A NKG2D-dependent cytolytic assay and staining with a recombinant NKG2D-Fc fusion protein showed that calcium chelation impaired the functional ability of NKG2D-ligands induced by HDAC-inhibitor treatment. The HDAC-inhibitor induced cell surface expression of ULBP2, but not MICA/B, was sensitive to treatment calmidazolium and trifluoperazine, two agents known to block calcium signaling. siRNA-mediated knock-down of the calcium-regulated proteins calmodulin or calpain did however not affect NKG2D-ligand cell surface expression on Jurkat T-cells. We further show that secretion and cell surface binding of the calcium-regulating protein galectin-1 is enhanced upon HDAC-inhibitor treatment of melanoma cells. However, binding of galectin-1 to cell surface glycoproteins was not critical for constitutive or HDAC-inhibitor induced MICA/B and ULBP2 cell surface expression. We provide evidence that MICA/B and ULBP2 cell surface expression is controlled differently by calcium, which adds to the increasing perception that cell surface expression of MICA/B and ULBP2 is controlled by distinct signal transduction pathways.
Original language | English |
---|---|
Journal | Molecular Immunology |
Volume | 53 |
Issue number | 3 |
Pages (from-to) | 255-264 |
Number of pages | 10 |
ISSN | 0161-5890 |
DOIs | |
Publication status | Published - 2013 |
- Base Sequence, Calcium Signaling, Calmodulin, Calpain, Cell Line, Tumor, Cell Membrane, Depsipeptides, GPI-Linked Proteins, Galectin 1, Gene Knockdown Techniques, Histone Deacetylase Inhibitors, Humans, Imidazoles, Intercellular Signaling Peptides and Proteins, Jurkat Cells, Ligands, Melanoma, RNA, Small Interfering, Trifluoperazine
Research areas
ID: 44562379