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

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serval:BIB_6006AA9F1FF7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Deletion of the RNA-binding proteins ZFP36L1 and ZFP36L2 leads to perturbed thymic development and T lymphoblastic leukemia.
Journal
Nature Immunology
Author(s)
Hodson D.J., Janas M.L., Galloway A., Bell S.E., Andrews S., Li C.M., Pannell R., Siebel C.W., MacDonald H.R., De Keersmaecker K., Ferrando A.A., Grutz G., Turner M.
ISSN
1529-2916[electronic], 1529-2908[linking]
Publication state
Published
Issued date
2010
Peer-reviewed
Oui
Volume
11
Number
8
Pages
717-724
Language
english
Notes
Erratum in: Nat Immunol. 2010 Oct;11(10):969. Comment in: Nat Immunol. 2010 Aug;11(8):697-8.
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.
Keywords
Amino Acid Sequence, Animals, Conserved Sequence, Humans, Immunophenotyping, Kaplan-Meier Estimate, Mice, Mice, Knockout, Molecular Sequence Data, Nuclear Proteins/deficiency, Nuclear Proteins/genetics, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/immunology, RNA-Binding Proteins/genetics, RNA-Binding Proteins/immunology, Receptor, Notch1/genetics, Receptor, Notch1/immunology, Receptors, Antigen, T-Cell/genetics, Receptors, Antigen, T-Cell/immunology, Sequence Alignment, T-Lymphocytes/immunology, Thymus Gland/growth & development, Thymus Gland/immunology, Transcription, Genetic, Tristetraprolin/deficiency, Tristetraprolin/genetics
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Web of science
Create date
02/02/2011 10:13
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20/08/2019 14:17
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