title: Characterization of 5' promoter and exon 1-3 polymorphism of the RAET1E gene.
abstract: NKG2D is an activating receptor utilized by natural killer (NK) cells that recognizes upregulated ligands on infected, tumorigenic and damaged cells, leading to their cytolysis. However, the NKG2D ligand (NKG2DL) system is very complex with eight known gene loci encoding slightly different molecules. Furthermore, most NKG2DL gene loci such as MICA and MICB are highly polymorphic with potential for functional differences. NKG2DL expression on tumors varies depending on the malignancy and tumors can also release soluble NKG2DL that exert anergic effects on NK cells when engagement with NKG2D occurs, allowing escape from NK cell immunosurveillance. We carried out RAET1E typing of IHW cell line DNA, including a 580 bp proximal promoter fragment and exons 1-3 identifying 13 of 15 known RAET1E alleles. We determined 7 polymorphisms within the promoter region, including 2 already known that contributed to 9 promoter types. RAET1E alleles with variability in the extracellular region also differed with respect to promoter type and one allele, RAET1E(∗)003, associated with 5 promoter types. We then identified putative transcription factor binding sites for RAET1E, and found 5 of the 7 promoter polymorphisms may disrupt these sites, abrogating binding of transcription factors and varying the potential level of expression.
authors.affiliation: Anthony Nolan Research Institute, Royal Free Hospital, Hampstead, London NW3 2QU, UK. Electronic address: steven.cox@anthonynolan.org.uk.
authors.forename: Steven T
authors.initials: ST
authors.lastname: Cox
authors.affiliation: Anthony Nolan Research Institute, Royal Free Hospital, Hampstead, London NW3 2QU, UK.
authors.forename: Hayley
authors.initials: H
authors.lastname: Pearson
authors.affiliation: Anthony Nolan Research Institute, Royal Free Hospital, Hampstead, London NW3 2QU, UK.
authors.forename: Raquel
authors.initials: R
authors.lastname: Laza-Briviesca
authors.affiliation: HLA Laboratory, Hospital Nacional de Clinicas, Cordoba, Argentina.
authors.forename: Susanna
authors.initials: S
authors.lastname: Pesoa
authors.affiliation: HLA Laboratory, Hospital Nacional de Clinicas, Cordoba, Argentina.
authors.forename: Carlos
authors.initials: C
authors.lastname: Vullo
authors.affiliation: Anthony Nolan Research Institute, Royal Free Hospital, Hampstead, London NW3 2QU, UK; UCL Cancer Institute, Royal Free Campus, London NW3 2QG, UK.
authors.forename: J Alejandro
authors.initials: JA
authors.lastname: Madrigal
authors.affiliation: Anthony Nolan Research Institute, Royal Free Hospital, Hampstead, London NW3 2QU, UK; UCL Cancer Institute, Royal Free Campus, London NW3 2QG, UK.
authors.forename: Aurore
authors.initials: A
authors.lastname: Saudemont
mesh_terms: D001665:Binding Sites / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D005091:Exons / Q000235:genetics*; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D015166:Monitoring, Immunologic; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation; D019139:Tumor Escape
chemical_list: D002352:Carrier Proteins; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; C488760:RAET1E protein, human
keywords: Immunosurveillance; Ligand; NK cell; NKG2D; RAET1E; ULBP4