TGF-β-mediated phosphorylation of hnRNP E1 induces EMT via transcript-selective translational induction of Dab2 and ILEI

A Chaudhury, GS Hussey, PS Ray, G Jin, PL Fox… - Nature cell …, 2010 - nature.com
Nature cell biology, 2010nature.com
Transforming growth factor-β (TGF-β) induces epithelial–mesenchymal transdifferentiation
(EMT) accompanied by cellular differentiation and migration,,,,. Despite extensive
transcriptomic profiling, the identification of TGF-β-inducible, EMT-specific genes has met
with limited success. Here we identify a post-transcriptional pathway by which TGF-β
modulates the expression of EMT-specific proteins and of EMT itself. We show that
heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) binds a structural, 33-nucleotide …
Abstract
Transforming growth factor-β (TGF-β) induces epithelial–mesenchymal transdifferentiation (EMT) accompanied by cellular differentiation and migration,,,,. Despite extensive transcriptomic profiling, the identification of TGF-β-inducible, EMT-specific genes has met with limited success. Here we identify a post-transcriptional pathway by which TGF-β modulates the expression of EMT-specific proteins and of EMT itself. We show that heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) binds a structural, 33-nucleotide TGF-β-activated translation (BAT) element in the 3′ untranslated region of disabled-2 (Dab2) and interleukin-like EMT inducer (ILEI) transcripts, and represses their translation. TGF-β activation leads to phosphorylation at Ser 43 of hnRNP E1 by protein kinase Bβ/Akt2, inducing its release from the BAT element and translational activation of Dab2 and ILEI messenger RNAs. Modulation of hnRNP E1 expression or its post-translational modification alters the TGF-β-mediated reversal of translational silencing of the target transcripts and EMT. These results suggest the existence of a TGF-β-inducible post-transcriptional regulon that controls EMT during the development and metastatic progression of tumours.
nature.com