%0 journal article
%@ 1529-2908
%A Hodson, D.J., Janas, M.L., Galloway, A., Bell, E.E., Andrews, S., Li, C.M., Pannell, R., Siebel, C.W., MacDonald, H.R., De Keersmaecker, K., Ferrando, A.A., Gruetz, G., Turner, M.

%D 2010
%J Nature Immunology
%N 8
%P 717-724 
%R doi:10.1038/ni.1901
%T Deletion of the RNA-binding proteins ZFP36L1 and ZFP36L2 leads to perturbed thymic development and T lymphoblastic leukemia
%U https://doi.org/10.1038/ni.1901
8 
%X 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 β-selection checkpoint without first expressing the T cell antigen receptor β-chain (TCRβ). 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.