18 research outputs found
ISONICOTINIC ACID HYDRAZIDE IN THE TREATMENT OF CUTANEOUS TUBERCULOSIS: PRELIMINARY REPORT.
Toll-like Receptor Cross-hyporesponsiveness is Functional in Interleukin-1-receptor-associated Kinase-1 (IRAK-1)-deficient Macrophages: Differential Role Played by IRAK-1 in Regulation of Tumour Necrosis Factor and Interleukin-10 Production
Deletion of the RNA-binding proteins ZFP36L1 and ZFP36L2 leads to perturbed thymic development and T lymphoblastic leukemia.
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 (TCRbeta). 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