Upon the loss of glucose as the main carbon source cells have developed different mechanisms in order to adapt to this stress and promote survival. In Saccharomyces cerevisiae one such mechanism is acetylation, a post-translational modification performed by a lysine acetyltransferase (KAT) complex, such as NuA4, which has been previously shown to regulate different glucose metabolic pathways. Despite its known role upon glucose starvation, it is not currently understood how NuA4 itself is regulated in response to acute glucose deprivation (GD). I determine here that NuA4 complex protein levels (including catalytic protein Esa1), structure, activity, and localization are not impacted by acute GD. Despite GD showing no impact to NuA4 itself, it does result in the remodelling of both the interactome and acetylome of the complex where 160 proteins were identified to change interaction with Esa1-TAP and 93 acetylation sites were identified. As well GD results in a shift in localization of interacting proteins from nuclear upon standard growth to cytoplasmic. As well the changing interactome shows enrichment for proteins related to regulation of transcription and translation, metabolic pathways like glycolysis and gluconeogenesis, and others related to the cellular stress response. From the interactome three sets of proteins, Pab1, Eaf5/7/3, and Fas1 and Fas2, were studied further to greater characterize their interaction with NuA4 as they change interaction upon GD. Eaf7 protein levels were shown to decrease upon GD and both Fas1 and Fas2 levels were shown to increase in response to NuA4 deletion mutants. Together this work provides a greater understanding of the cellular response to acute GD stress, and how NuA4 plays a role in response to that stress in order to promote cell survival.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/35810 |
| Date | January 2017 |
| Creators | Czosniak, David |
| Contributors | Baetz, Kristin |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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