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Nat Immunol. 2010 Aug;11(8):717-24. doi: 10.1038/ni.1901. Epub 2010 Jul 11.

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

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1
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK.

Erratum in

  • Nat Immunol. 2010 Oct;11(10):969.

Abstract

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.

Comment in

PMID:
20622884
PMCID:
PMC2953641
DOI:
10.1038/ni.1901
[Indexed for MEDLINE]
Free PMC Article

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