title: The RNA binding protein IMP3 facilitates tumor immune escape by downregulating the stress-induced ligands ULPB2 and MICB.
abstract: Expression of the stress-induced ligands MICA, MICB and ULBP 1-6 are up-regulated as a cellular response to DNA damage, excessive proliferation or viral infection; thereby, they enable recognition and annihilation by immune cells that express the powerful activating receptor NKG2D. This receptor is present not exclusively, but primarily on NK cells. Knowledge about the regulatory mechanisms controlling ULBP expression is still vague. In this study, we report a direct interaction of the oncogenic RNA binding protein (RBP) IMP3 with ULBP2 mRNA, leading to ULBP2 transcript destabilization and reduced ULBP2 surface expression in several human cell lines. We also discovered that IMP3 indirectly targets MICB with a mechanism functionally distinct from that of ULBP2. Importantly, IMP3-mediated regulation of stress-ligands leads to impaired NK cell recognition of transformed cells. Our findings shed new light on the regulation of NKG2D ligands and on the mechanism of action of a powerful oncogenic RBP, IMP3.
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Dominik
authors.initials: D
authors.lastname: Schmiedel
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Julie
authors.initials: J
authors.lastname: Tai
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Yamin
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Berhani
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Bauman
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Ofer
authors.identifier: http://orcid.org/0000-0002-9354-1855
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D045744:Cell Line, Tumor; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007694:Killer Cells, Natural / Q000276:immunology; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D019139:Tumor Escape
chemical_list: D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; C498780:IGF2BP3 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C098080:MICB antigen; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016601:RNA-Binding Proteins; C423230:ULBP2 protein, human
keywords: IGF2BP3; IMP3; RNA-binding protein; ULBP2; human; immune evasion; immunology