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dc.contributor.advisor Gromeier, Matthias en_US
dc.contributor.author Goetz, Christian en_US
dc.date.accessioned 2012-05-29T16:46:16Z
dc.date.available 2013-05-24T04:30:06Z
dc.date.issued 2011 en_US
dc.identifier.uri http://hdl.handle.net/10161/5715
dc.description Dissertation en_US
dc.description.abstract <p>Signaling pathways converge on the translation machinery and influence protein synthesis globally or specifically on certain classes of transcripts. The experiments described in this thesis focus on regulation of translation initiation through the cap-binding protein eIF4E. </p><p>Aberrant regulation of eIF4E has important roles in several pathologies and, most notably, in tumorigenesis. Nevertheless, the understanding of the molecular con-sequences of changes in eIF4E activity remains incomplete. We employ a cell-free system to demonstrate that eIF4E function is required for efficient cap-dependent translation but inhibitory for translation of both cellular and viral RNAs relying on cap-independent mechanisms. Furthermore, we show that phosphorylation of eIF4E favors cap-independent translation in vitro. </p><p>To verify that our findings in the cell-free system are representative of an in vivo system, we also analyzed growth of an oncolytic poliovirus, relying purely on cap-independent translation, in the context of varying activity of signaling pathways. Data obtained from this virus helps to confirm that phosphorylation of eIF4E does indeed result in increased cap-independent translation. Additionally, these experiments provide important information for the clinical application of this oncolytic poliovirus, as they help to explain virus specificity and might allow for rational patient selection.</p> en_US
dc.subject Cellular Biology en_US
dc.subject Molecular Biology en_US
dc.subject eIF4E en_US
dc.subject eIF4G en_US
dc.subject IRES en_US
dc.subject Mnk en_US
dc.subject Ras en_US
dc.subject Translation en_US
dc.title eIF4E Phosphorylation Balances Cap-dependent and Cap-independent Translation Initiation en_US
dc.type Dissertation en_US
dc.department Molecular Cancer Biology en_US
duke.embargo.months 12 en_US

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