Deletion of the RNA-binding proteins ZFP36L1 and ZFP36L2 leads to perturbed thymic development and T lymphoblastic leukemia

作者：Hodson Daniel J; Janas Michelle L; Galloway Alison; Bell Sarah E; Andrews Simon; Li Cheuk M; Pannell Richard; Siebel Christian W; MacDonald H Robson; De Keersmaecker Kim; Ferrando Adolfo A; Grutz Gerald; Turner Martin^*

来源：Nature Immunology, 2010, 11(8): 717-U84.

DOI：10.1038/ni.1901

ZFP36L1 and ZFP36L2 are RNA-binding proteins (RBPs) that interact with AU-rich elements in the 3' untranslated region of mRNA, which leads to mRNA degradation and translational repression. Here we show that mice that lacked ZFP36L1 and ZFP36L2 during thymopoiesis developed a T cell acute lymphoblastic leukemia (T-ALL) dependent on the oncogenic transcription factor Notch1. Before the onset of T-ALL, thymic development was perturbed, with accumulation of cells that had passed through the beta-selection checkpoint without first expressing the T cell antigen receptor beta-chain (TCR beta). Notch1 expression was higher in untransformed thymocytes in the absence of ZFP36L1 and ZFP36L2. Both RBPs interacted with evolutionarily conserved AU-rich elements in the 3' untranslated region of Notch1 and suppressed its expression. Our data establish a role for ZFP36L1 and ZFP36L2 during thymocyte development and in the prevention of malignant transformation.

• 出版日期2010-8
• 单位河北医科大学