منابع مشابه
4E-BP restrains eIF4E phosphorylation
In eukaryotes, mRNA translation is dependent on the cap-binding protein eIF4E. Through its simultaneous interaction with the mRNA cap structure and with the ribosome-associated eIF4G adaptor protein, eIF4E physically posits the ribosome at the 5' extremity of capped mRNA. eIF4E activity is regulated by phosphorylation on a unique site by the eIF4G-associated kinase MNK. eIF4E assembly with the ...
متن کاملmTOR inhibitor efficacy is determined by the eIF4E/4E-BP ratio
The mammalian/mechanistic target of rapamycin (mTOR) is a multifunctional serine/threonine kinase that is hyperactivated in cancer [1]. mTOR forms two distinct complexes, mTORC1 and 2. mTORC1 stimulates translation and perturbs energy metabolism to drive cell proliferation and growth, whereas mTORC2 regulates cytoskeletal organization and cell survival by stimulating AGC kinases (e.g. AKT). The...
متن کاملThe 4E-BP Caf20p Mediates Both eIF4E-Dependent and Independent Repression of Translation
Translation initiation factor eIF4E mediates mRNA selection for protein synthesis via the mRNA 5'cap. A family of binding proteins, termed the 4E-BPs, interact with eIF4E to hinder ribosome recruitment. Mechanisms underlying mRNA specificity for 4E-BP control remain poorly understood. Saccharomyces cerevisiae 4E-BPs, Caf20p and Eap1p, each regulate an overlapping set of mRNAs. We undertook glob...
متن کاملThe translational repressor 4E-BP called to order by eIF4E: new structural insights by SAXS
eIF4E binding protein (4E-BP) inhibits translation of capped mRNA by binding to the initiation factor eIF4E and is known to be mostly or completely unstructured in both free and bound states. Using small angle X-ray scattering (SAXS), we report here the analysis of 4E-BP structure in solution, which reveals that while 4E-BP is intrinsically disordered in the free state, it undergoes a dramatic ...
متن کاملeIF4E/4E-BP ratio predicts the efficacy of mTOR targeted therapies.
Active-site mTOR inhibitors (asTORi) hold great promise for targeting dysregulated mTOR signaling in cancer. Because of the multifaceted nature of mTORC1 signaling, identification of reliable biomarkers for the sensitivity of tumors to asTORi is imperative for their clinical implementation. Here, we show that cancer cells acquire resistance to asTORi by downregulating eukaryotic translation ini...
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ژورنال
عنوان ژورنال: Translation
سال: 2013
ISSN: 2169-0731
DOI: 10.4161/trla.25819