Investigating the effects of increased levels of the translation elongation factor eEF1A within eukaryotic cells

Tarrant, Daniel.S.J (2015) Investigating the effects of increased levels of the translation elongation factor eEF1A within eukaryotic cells. Doctor of Philosophy (PhD) thesis, University of Kent,.

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Abstract

The highly conserved eukaryotic elongation factor 1A (eEF1A) plays a canonical role in translation elongation, where it is responsible for delivering the aminoacylated tRNA to the A-site of the 80S ribosome. Further to this essential role it is reported to be involved in a plethora of moonlighting functions that are not fully characterised or understood. One of the human isoforms, eEF1A2, is known to induce cancer when expressed in non-native tissues, although the mechanism by which it promotes tumour growth is not yet known. In this study we have characterised eEF1A overexpression in yeast and provided evidence to suggest that elevated levels of eEF1A result spindle defects which lead to chromosomal abnormalities that have the potential to induce uncontrolled cell growth in human cells. Moreover, we have confirmed conservation of this chromosomal abnormality in human cell lines suggesting that the mechanism that eEF1A utilises to induce these effects are highly conserved. We have also observed that in yeast, eEF1A overexpression results in increased metabolic activity, a hallmark of cancer cells. We hypothesise that eEF1A interacts with the dynactin complex, a regulator of spindle dynamics, resulting in aberrant spindle formation. This in turn leads to chromosomal abnormalities that appear toxic to the cell. Cells appear to overcome the toxicity induced by eEF1A by suppressing plasmid copy number to the lowest levels possible. This however, brings its own problems and appears to result in synthetic effects together with eEF1A overexpression.

Item Type: Thesis (Doctor of Philosophy (PhD))
Thesis advisor: Gourlay, Campbell
Thesis advisor: von der Haar, Tobias
Uncontrolled keywords: eEF1A TEF1 Elongation Factor Cell cycle Dynactin Cancer
Subjects: Q Science > QH Natural history > QH581.2 Cell Biology
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Users 1 not found.
Date Deposited: 28 Apr 2015 17:00 UTC
Last Modified: 29 May 2019 14:27 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/48089 (The current URI for this page, for reference purposes)
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