Abstract:
:Transcript-selective translational regulation of epithelial-mesenchymal transition (EMT) by transforming growth factor-β (TGF-β) is directed by the hnRNP E1-containing TGF-β-activated-translational (BAT) mRNP complex. Herein, eukaryotic elongation factor-1 A1 (eEF1A1) is identified as an integral component of the BAT complex. Translational silencing of Dab2 and ILEI, two EMT transcripts, is mediated by the binding of hnRNP E1 and eEF1A1 to their 3'UTR BAT element, whereby hnRNP E1 stalls translational elongation by inhibiting the release of eEF1A1 from the ribosomal A site. TGF-β-mediated hnRNP E1 phosphorylation, through Akt2, disrupts the BAT complex, thereby restoring translation of target EMT transcripts. Attenuation of hnRNP E1 expression in two noninvasive breast epithelial cells (NMuMG and MCF-7) not only induced EMT but also enabled cells to form metastatic lesions in vivo. Thus, translational regulation by TGF-β at the elongation stage represents a critical checkpoint coordinating the expression of EMT transcripts required during development and in tumorigenesis and metastatic progression.
journal_name
Mol Celljournal_title
Molecular cellauthors
Hussey GS,Chaudhury A,Dawson AE,Lindner DJ,Knudsen CR,Wilce MC,Merrick WC,Howe PHdoi
10.1016/j.molcel.2011.02.003subject
Has Abstractpub_date
2011-02-18 00:00:00pages
419-31issue
4eissn
1097-2765issn
1097-4164pii
S1097-2765(11)00086-4journal_volume
41pub_type
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