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The roles of RAS in controlling cell fate - a yeast model of oncogenic potential

Dresel, Fiona (2022) The roles of RAS in controlling cell fate - a yeast model of oncogenic potential. Master of Science by Research (MScRes) thesis, University of Kent,. (doi:10.22024/UniKent/01.02.94143) (KAR id:94143)


The small GTPase Ras plays an important role in cell growth and proliferation. Human diseases, like cancer, can be caused by mutations leading to constantly activated Ras proteins. Post-translational modifications ensure Ras localisation and thus its proper function. However, the precise mechanisms of those modifications in controlling the localisation of Ras are still poorly understood. Our previous studies have shown that phosphorylation of the Serine225 residue of Ras is important in cell growth and proliferation in the yeast S. cerevisiae. Serine225 modifications have resulted in mislocalisation of Ras2 within the cell driving the cells towards a quiescent state of growth through aberrant Ras/cAMP/PKA signalling. In this study we show that the combination of an increased copy number and mutation leads to an altered cell fate supporting evidence that both Ras mutation and gene duplication are often necessary to cause cancer. We also show that the deletion of CUP9 could rescue the toxic effects of Ras2S225 mutant alleles including growth, viability, and respiratory defects. In addition, MET-auxotrophy could be overcome in Ras2S225 mutants. Our results demonstrate that the Serine225 residue is important in regulating Ras2 localisation and its activity co-ordinating nutrient sensing with cell growth and proliferation. We highlight the importance of post-translational modifications of Ras2 but also other regions outside the Ras GTPase domain e.g. other nutritional pathways controlled or modulated by Ras in yeast in cell fate. Our findings have implications for the development of novel therapeutic approaches for cancers driven by oncogenic Ras proteins.

Item Type: Thesis (Master of Science by Research (MScRes))
Thesis advisor: Gourlay, Campbell
DOI/Identification number: 10.22024/UniKent/01.02.94143
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > Biosciences
SWORD Depositor: System Moodle
Depositing User: System Moodle
Date Deposited: 26 Apr 2022 07:09 UTC
Last Modified: 27 Apr 2022 08:32 UTC
Resource URI: (The current URI for this page, for reference purposes)

University of Kent Author Information

Dresel, Fiona.

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