RNA-binding proteins regulate the expression of the immune activating ligand MICB

Daphna Nachmani, Tony Gutschner, Adi Reches, Sven Diederichs and Ofer Mandelboim ()
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Daphna Nachmani: 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
Tony Gutschner: Helmholtz-University-Group "Molecular RNA Biology & Cancer", German Cancer Research Center DKFZ and Institute of Pathology, University Hospital Heidelberg
Adi Reches: 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
Sven Diederichs: Helmholtz-University-Group "Molecular RNA Biology & Cancer", German Cancer Research Center DKFZ and Institute of Pathology, University Hospital Heidelberg
Ofer Mandelboim: 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

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: Abstract The recognition of stress-induced ligands by the activating receptor NKG2D expressed on cytotoxic lymphocytes is crucial for the prevention and containment of various diseases and is also one of the best-studied examples of how danger is sensed by the immune system. Still, however, the mechanisms leading to the expression of the NKG2D ligands are far from being completely understood. Here, we use an unbiased and systematic RNA pull-down approach combined with mass spectrometry to identify six RNA-binding proteins (RBPs) that bind and regulate the expression of MICB, one of the major stress-induced ligands of NKG2D. We further demonstrate that at least two of the identified RBPs function during genotoxic stress. Our data provide insights into stress recognition and hopefully open new therapeutic venues.

Date: 2014
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DOI: 10.1038/ncomms5186

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