Nachmani Daphna, Gutschner Tony, Reches Adi, Diederichs Sven, Mandelboim Ofer
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, 91120 Jerusalem, Israel.
Helmholtz-University-Group "Molecular RNA Biology & Cancer", German Cancer Research Center DKFZ and Institute of Pathology, University Hospital Heidelberg, D-69120 Heidelberg, Germany.
Nat Commun. 2014 Jun 13;5:4186. doi: 10.1038/ncomms5186.
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.
细胞毒性淋巴细胞上表达的激活受体NKG2D对应激诱导配体的识别，对于预防和控制各种疾病至关重要，也是免疫系统感知危险的研究得最为透彻的例子之一。然而，导致NKG2D配体表达的机制仍远未完全被理解。在此，我们采用无偏向性的系统RNA下拉方法并结合质谱分析，以鉴定出六种与NKG2D的主要应激诱导配体之一MICB结合并调节其表达的RNA结合蛋白（RBP）。我们进一步证明，至少两种已鉴定的RBP在基因毒性应激期间发挥作用。我们的数据为应激识别提供了见解，并有望开辟新的治疗途径。
