Protein translation in mammalian cells can be divided into three stages: initiation, elongation, and termination, which require several factors. The peptide elongation factor 1A (eEF1A-1), which was formerly referred to as eEF-1alpha, is a guanosine triphosphate (GTP) binding protein and it is responsible for bringing aminoacyl-tRNA to the ribosomes in the process of protein synthesis. The S1/eEF1A-2 factor also referred to as S1, is an isoform of eEF1A-1. Both proteins are expressed from two distinct genes and share 92% identity in their amino acid sequences. Besides the tissue specific expression S1/eEF1A-2, little is known about the functions of the S1/cEF1A-2 isoform. The objective of this thesis is Thus to investigate the function of the newly discovered peptide elongation factor A-2. The fact that the eEF1A-1 and Sl/eEF1A-2 isoforms' expressions are inversely controlled during development, led me to hypothesise that S1/eEF1A-2 down-regulates eEF1A-1 expression. The goal of the present work was to establish whether S1/eEF1A-2 is responsible for the down-regulation of eEF1A-1 during development in brain, heart and muscle, and how its expression influences cell biology. To address this hypothesis, several cell lines were transduced with an adenovirus expressing S1/eEF1A-2. Ectopic expression of S1/eEF1A-2 in the cardiomyocyte cell line H9c2 led to a down-regulation of eEF1A-1. Similar findings were observed in neuron-differentiated P19 cells, Hela cells, and WI38 cells. Furthermore, S1/eEF1A-2 expression led to a reduced rate of peptide elongation as demonstrated by ribosomal transit time analyses. My data suggest that S1/eEF1A-2 may compete with eEF1A-1 in peptide elongation, leading to a reduced elongation rate, which could be responsible for the relative down-regulation of eEF1A-1. This would imply that terminally differentiated cells, which express high levels of S1/eEF1A-2 (neurones, myocytes, and cardiomyocytes), have a distinct kinetic of peptide elonga
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.36876 |
| Date | January 2001 |
| Creators | Bourbeau, Denis, 1971- |
| Contributors | Wang, Eugenia (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001803868, proquestno: NQ69972, Theses scanned by UMI/ProQuest. |
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