Regulation of Eukaryotic Translation Initiation by Signal Transduction
Date
2012
Authors
Advisors
Journal Title
Journal ISSN
Volume Title
Repository Usage Stats
views
downloads
Abstract
Eukaryotic translation initiation is a rate-limiting step of protein synthesis and is controlled by signal transduction in response to various extracellular cues and stresses. This thesis is focused on the eukaryotic initiation factor 4G (eIF4G), which participates in multiple steps of initiation: (i) eIF4G interaction with polyA-binding protein (PABP) links the 5' pre-initiation complex to the 3' poly(A) tail of mRNAs; (ii) eIF4G recruits 40S ribosomal subunit to mRNAs through interactions with the m7-G cap binding protein eIF4E; (iii) eIF4G binds to the eIF4E kinase, mitogen activated protein kinase (MAPK) interacting kinase 1 (Mnk1), modulating eIF4E phosphorylation. I studied how eIF4G function is affected by viral infection, mitogenic stimulation and during mitosis.
First, I reported that herpes simplex virus 1 (HSV-1) infection leads to re-localization of PABP to the nucleus, dissociating it from translation initiation machinery. Next, I showed that MAPK-mediated phosphorylation of Mnk1 leads to Mnk1 conformational changes, enhancing its binding to eIF4G and, hence, increasing phosphorylation of its substrate, eIF4E. Finally, I demonstrated that Cdk1/cyclin B1 directly phosphorylates eIF4G in mitosis and speculated on the role of this phosphorylation event in mitotic translation. In summary, my work demonstrated that eIF4G plays key roles in the regulation of the translational response to viral infection, growth signaling and cell cycle progression.
Type
Department
Description
Provenance
Subjects
Citation
Permalink
Citation
Shveygert, Mayya (2012). Regulation of Eukaryotic Translation Initiation by Signal Transduction. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/5817.
Collections
Except where otherwise noted, student scholarship that was shared on DukeSpace after 2009 is made available to the public under a Creative Commons Attribution / Non-commercial / No derivatives (CC-BY-NC-ND) license. All rights in student work shared on DukeSpace before 2009 remain with the author and/or their designee, whose permission may be required for reuse.