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Investigating the role of DDX28 as a novel regulator of the hypoxic cap dependent translation initiation complex

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dc.contributor.advisor Uniacke, Jim Evagelou, Sonia 2018-11-15T13:42:48Z 2018-09 2018-11-05 2018-11-15
dc.description.abstract The most common form of translation initiation in eukaryotes requires recruitment of the eIF4F complex to the m7GTP cap located at the 5’ end of all cellular mRNAs. eIF4F is composed of the cap-binding factor eIF4E, the RNA helicase eIF4A, and the scaffolding protein eIF4G, which together function to initiate translation. However, in response to hypoxia, a common feature of several physiological and pathological processes, eIF4E is inhibited. Hypoxic cells maintain translation of select transcripts by utilizing the eIF4E homologue, eIF4E2, as an alternative cap-binding protein as part of the eIF4FH complex. We have identified DDX28 as a novel regulator of eIF4FH by demonstrating that knocking-down DDX28 results in an overall increase in cap-bound eIF4E2 and eIF4E2-mediated translation under hypoxia. Additionally, depletion of DDX28 confers a proliferative advantage to cells grown in hypoxic conditions, which we suspect is a consequence of the translational upregulation of a subset of hypoxic mRNAs. en_US
dc.language.iso en en_US
dc.rights Attribution-NonCommercial-NoDerivatives 4.0 International *
dc.rights.uri *
dc.subject Oxygen en_US
dc.subject Hypoxia en_US
dc.subject Translation en_US
dc.subject Cancer en_US
dc.subject cap-binding protein en_US
dc.subject Helicase en_US
dc.subject DDX28 en_US
dc.subject eIF4E2 en_US
dc.subject eIF4FH en_US
dc.subject m7GTP en_US
dc.subject Protein synthesis en_US
dc.subject mRNA en_US
dc.subject rHRE en_US
dc.subject DEAD-box en_US
dc.subject 5' cap en_US
dc.title Investigating the role of DDX28 as a novel regulator of the hypoxic cap dependent translation initiation complex en_US
dc.type Thesis en_US Molecular and Cellular Biology en_US Master of Science en_US Department of Molecular and Cellular Biology en_US
dc.description.embargo 2019-11-05
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Attribution-NonCommercial-NoDerivatives 4.0 International Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International